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Refining treatment options for mRCC

Repeat surgeries for glioblastoma may prolong survival

CASE STUDY

Capecitabine treatment in metastatic breast cancer

CONFERENCE

Crizotinib tops chemotherapy in ALK-positive NSCLC

Call for action to increase use of breast-conserving surgery

NEWS

HK researchers pioneer computer-assisted surgery for bone tumors

BRIEFS

Regorafenib obtains FDA approval for advanced CRC

Thunder god strikes pancreatic cancer

June 2012November–December 2012

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Nov-Dec 2012 3

Refining treatment options for mRCC

Naomi Rodrig

A number of phase III trials reported at the recent Congress of the European Society of Medical Oncology (ESMO)

explored various treatment options for meta-static renal cell carcinoma (mRCC), and may have important implications for patients.

The COMPARZ1 trial – showed that pazopanib was as effective as sunitinib in first-line treatment of mRCC, but was associated with a lower incidence of side effects and better quality of life (QoL). [Abstract LBA8_PR]

In this global, 1,100-patient trial, the inves-tigators compared the efficacy, safety, and QoL for pazopanib vs sunitinib, which is considered the reference standard. The primary endpoint was noninferiority of progression-free survival (PFS). Key secondary endpoints included overall survival (OS), overall response rate (ORR), adverse events, and QoL.

“The results demonstrated noninferiority of pazopanib vs sunitinib in first-line treat-ment of mRCC,” reported lead investigator, Dr. Robert Motzer from the Memorial Sloan Kettering Cancer Center, New York, USA. “Median PFS by the treating physician’s assessment was 10.5 months for pazopanib vs 10.2 months for sunitinib [hazard ratio (HR), 0.998]. The respective ORRs were 31 vs 25 percent [p=0.03].”

He added that some of the side effects recognized to be troublesome to patients, such as fatigue and hand-foot syndrome, occurred more frequently with sunitinib than pazopanib. “Differences in 11 of 14 QoL domains were small but statistically signifi-cant, all favoring pazopanib, which suggests

improved tolerability of pazopanib over sunitinib,” Motzer said.

In the INTORSECT2 trial, temsirolimus (a mammalian target of rapamycin [mTOR] inhibitor) did not demonstrate superiority in survival over the VEGF tyrosine kinase inhib-itor (TKI) sorafenib in second-line treatment of mRCC. The trial included 511 patients whose disease progressed after first-line sunitinib therapy. Median PFS with temsiro-limus was 4.28 months vs 3.91 months with sorafenib. Median OS was 12.27 and 16.64 months, respectively.

“The data suggest that drugs which inhibit the VEGF pathway may be a better option than mTOR inhibitors for patients progressing on sunitinib,” said Dr. Thomas Hutson from Texas Oncology-Baylor Charles A Sammons Cancer Center, USA. “Hence, this trial will have impor-

Nov-Dec 2012 4

1. Pazopanib vs Sunitinib in the Treatment of Locally Advanced and/or metastatic RCC2. Temsirolimus vs Sorafenib as Second-line Therapy in Patients with Advanced RCC Who Have Failed First-line

Sunitinib3. Torisel and Avastin Combination Therapy

tant treatment implications for patients and physicians.” [Abstract LBA22_PR]

The open-label INTORACT3 study compared a combination of temsirolimus and bevaci-zumab with interferon plus bevacizumab as first-line treatment in 791 patients with predominantly clear cell mRCC. Median PFS for the temsirolimus combination was 9.1 months vs 9.3 months for the interferon group, and median OS was 25.8 and 25.5 months, respectively.

“Bevacizumab and temsirolimus offered no advantage over bevacizumab plus inter-

feron,” said Professor Brian Rini, of the Cleve-land Clinic, Case Western Reserve University, Cleveland, USA. “The two drugs target separate molecular pathways, and early results had seemed promising.” [Abstract LBA21_PR]

“These studies are significant because they increase our knowledge about the use of targeted treatment options,” remarked Professor Maria De Santis, Chair of the ESMO 2012 genitourinary track. “Most importantly, the COMPARZ trial allows us to define a standard option in the front-line treatment of RCC, because it was proven that pazopanib is noninferior to sunitinib.”

Br ie fsNov-Dec 2012 5

Vaccine shows promise in cervical cancerVGX-3100, a therapeutic HPV16/18 vaccine candidate, induces a robust HPV-specific im-

mune response in previously infected individuals, according to results of a phase I study. [Sci Transl Med 2012;4:155ra138; doi: 10.1126/scitranslmed. 3004414]

In the study, 18 women previously treated for grade 2 or 3 cervical intraepithelial neopla-sia received a three-dose intramuscular regimen of highly engineered plasmid DNA encod-ing HPV16 and HPV18 E6/E7 antigens, followed by VGX-3100 delivered by electroporation. The authors observed that HPV-specific CD8+ T cells were induced after vaccination with VGX-3100.

Immunization was well tolerated, with no serious or grade 3/4 adverse events or dose-limiting toxicity.

Regorafenib obtains FDA approval for advanced CRCRegorafenib has obtained early FDA approval for use in treat-

ment-refractory, metastatic colorectal cancer (mCRC).The approval, which came 1 month before FDA’s expected deci-

sion date, is based on results of the phase III CORRECT trial (n=760). In patients with mCRC that progressed after treatment with stan-dard therapies, regorafenib significantly improved overall survival (6.4 vs 5 months; HR, 0.77) and progression-free survival (1.9 vs 1.7 months; HR, 0.49) vs best supportive care alone. [ASCO 2012; abstract 3502]

Regorafenib is the second drug approved by the FDA for treat-ment of CRC since July 2012. The oral multi-kinase inhibitor targets a broad range of angiogenic, oncogenic, and stromal kinases. Common adverse effects include fatigue, hand-foot skin reactions, diarrhea, anorexia, voice changes, hypertension, muco-sitis, and rash.

Br ie fsNov-Dec 2012 6

Thunder god strikes pancreatic cancer

Minnelide, an experimental compound derived from a plant product known

as triptolide, demonstrated high efficacy in killing pancreatic tumor cells and shrink-ing tumors in a preclinical study. [Sci Transl Med 2012;4:156ra139. doi: 10.1126/scitrans-lmed.3004334]

Triptolide has a long history of use in tradi-tional Chinese medicine, where it is known as “thunder god vine”. It inhibits the heat shock protein 70 (HSP70), which protects cells from dying and is overexpressed in pancreatic can-cer. As triptolide is not water-soluble, researchers modified the compound into minnelide, which is tweaked for more effective delivery to pancreatic cells.

In cell lines and in mice with transplanted human pancreatic tumors, minnelide was highly effective in reducing pancreatic tumor growth and spread, and improving survival. The researchers plan to study its toxicity in larger animals before moving on to early clinical trials.

Conference CoverageNov-Dec 2012 7European Society of Medical Oncology (ESMO) 2012 Congress, 28 September-2 October 2012, Vienna, Austria – Naomi Rodrig reports

Targeted therapy with crizotinib pro-longed progression-free survival (PFS) and improved response rates over

standard chemotherapy with pemetrexed or docetaxel in patients with advanced anaplas-tic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), data from the phase III PROFILE 1007 study showed.

According to lead author Dr. Alice Shaw from Massachusetts General Hospital in Bos-ton, USA, rearrangements of the ALK gene are found in about 6 percent of all lung can-cers, leading to constitutive kinase activation and oncogene addiction. In previous studies, crizotinib induced significant clinical respons-es in patients with ALK-positive tumors.

In the current multinational trial, 318 patients were randomized to crizotinib 250 mg bid or chemotherapy (pemetrexed 500 mg/m2 or docetaxel 75 mg/m2) un-til disease progression or death. The pri-mary endpoint was PFS by independent radiology review.

“Crizotinib improved PFS to a median of 7.7 months vs 3.0 months in the chemotherapy arm [hazard ratio (HR), 0.49; p<0.0001]. The median PFS was 4.2 months on pemetrexed and 2.6 months on docetaxel,” reported Shaw.

The overall response rate was also signifi-cantly higher in those treated with crizotinib (65.7 vs 19.5 percent; p<0.0001). “The overall survival [OS] analysis is still immature, as not enough events have occurred to draw mean-

ingful conclusions,” she said. “Moreover, there was significant crossover, as patients who progressed on chemotherapy were al-lowed to receive crizotinib. Hence, the major-ity of patients in the chemotherapy arm actu-ally did receive crizotinib, which makes the determination of OS benefit very challeng-ing.”

Vision disorders, elevated transaminases, pulmonary embolism and several other ad-verse events occurred more frequently in the crizotinib arm, but these were generally toler-able and manageable, according to Shaw.

“Importantly, patient-reported outcomes

Crizotinib tops chemotherapy in ALK-positive NSCLC

in terms of lung cancer symptoms [chest pain, cough and dyspnea] and global quality of life favored crizotinib over chemotherapy,” she noted.

“In ALK-positive patients previously treat-ed with first-line platinum-based chemother-apy, crizotinib is superior to standard single-agent chemotherapy in terms of response, PFS and quality of life. These results establish crizotinib as the standard of care for patients with advanced, previously treated, ALK-pos-itive lung cancer,” she concluded. [Abstract 1 LBA_PR]

“The data demonstrate a clear and strong signal of activity, as objective response was tripled with crizotinib, and PFS prolonged by 4.7 months compared with chemothera-

py,” remarked invited discussant, Professor Jean-Charles Soria of Villejuif, France. “Fur-thermore, the median time to response with crizotinib was 6.3 weeks vs 12.6 weeks for chemotherapy. Comparison with historical data suggests that crizotinib has changed the natural history of the disease, extending OS from 9 to 22 months.”

He argued that given these benefits, molecular profiling of lung cancers should routinely test not only EGFR but also ALK status.

“Further studies are needed to elucidate when and how to integrate crizotinib in the management of metastatic NSCLC, including in patients who did not receive previous therapy for advanced disease,” Soria suggested.

Promising new data from phase I and II trials suggest that drug combinations may slow or prevent the development

of resistance to BRAF inhibitors, which are currently used to treat metastatic melanoma.

BRAF mutations occur in about 50 to 60 percent of melanomas, and earlier trials with BRAF-targeting agents showed they can quickly shrink melanoma tumors in selected patients. However, the benefits proved short-lived, as the tumors developed resistance to these drugs.

BRIM-7 (BRAF Inhibitor in Melanoma-7), an ongoing phase Ib trial, showed that the combination of the MEK inhibitor GDC-0973

and the BRAF inhibitor vemurafenib can be delivered safely in patients with locally ad-vanced/unresectable or metastatic melanoma carrying a BRAF V600 mutation, according to Dr. Rene Gonzalez of the University of Colo-rado Denver, USA.

“BRAF inhibition has resulted in high re-sponse rates and improved survival in pa-tients with BRAF mutated melanoma,” he said. “One of several mechanisms of resis-tance has been reactivation of the MAPK pathway. Preclinical models show that com-bined inhibition of BRAF and MEK can delay the acquisition of resistance compared with BRAF inhibitor monotherapy. Inhibition of the pathway downstream from BRAF with GDC-0973 could theoretically overcome or delay this resistance mechanism.”

The study was not designed to evaluate ef-ficacy. “Early data in a small number of pa-

Dual therapy may improve melanoma outcomes

Combined inhibition of BRAF and MEK can delay the

acquisition of resistance

tients did show tumor reduction, but it would be premature to comment on efficacy based on these preliminary results, and further re-search is warranted,” suggested Gonzalez. [Abstract 28 LBA_PR]

In addition, Dr. Georgina Long from West-mead Hospital and the Melanoma Institute Australia, North Sydney, Australia reported that combining dabrafenib (a BRAF inhibitor) and trametinib (a MEK inhibitor) provided a clinically meaningful improvement in pro-gression-free survival (PFS), response rate, and duration of response in 162 patients with

melanoma that had BRAF V600 mutations. [Abstract 27LBA_PR]

Patients received either dabrafenib 150 mg twice daily; dabrafenib twice daily plus tra-metinib 1 mg once daily; or dabrafenib twice daily plus trametinib 2 mg once daily. The combination prolonged PFS from 5.8 months on dabrafenib monotherapy to 9.4 months, representing a 60 percent improvement. Among patients who received both doses of trametinib, 41 percent were progression free 12 months after treatment began, vs 9 percent in the monotherapy arm.

Two studies that evaluated the optimal duration of trastuzumab therapy in patients with early HER2/neu-positive

breast cancer suggest that extending or short-ening the treatment has no significant benefit, thus confirming the current 1-year standard of care.

In the HERA (Herceptin Adjuvant) trial, which enrolled about 5,102 patients with previous surgery +/- neoadjuvant therapy between 2001 and 2005, patients were ran-domized to receive trastuzumab every 3 weeks for 1 year (n=1,703) or 2 years (n=1,701), or observation. [Abstract 6 LBA_PR]

“As of 12 April 2012, the unadjusted haz-ard ratio [HR] for a woman experiencing disease relapse in the 2-year treatment arm vs the 1-year arm was 0.99 [p=0.86],” reported Professor Richard Gelber of Harvard Medi-cal School and Dana-Farber Cancer Institute, Boston, USA. “The overall survival [OS] rate in the two arms was comparable [HR, 1.05; p=0.6333], indicating that 1-year of treatment with the targeted trastuzumab is as good as 2 years of treatment.”

“The prolonged benefit in disease-free

survival [DFS] and OS of 1-year trastuzum-ab over no trastuzumab is remarkably reas-suring for patients, showing that the benefit is not lost after some years,” he remarked. Ongoing trials are also testing whether com-bining trastuzumab with other anti-HER2 agents such as pertuzumab or lapatinib) might further improve outcomes.”

The PHARE (Protocol of Herceptin Adju-

HER2-positive BC: One-year trastuzumab treatment remains standard of care

Conference CoverageNov-Dec 2012 9vant with Reduced Exposure) trial, a random-ized, noninferiority study by the French Na-tional Cancer Institute, compared a shorter trastuzumab exposure of 6 months vs the standard 12 months, recruiting more than 3,380 patients. The primary endpoint was DFS according to a noninferiority hypothesis. [Abstract 5 LBA_PR]

The median follow-up was 42.5 months. At the time of the analysis 395 DFS events were reported. “According to the trial de-sign, which allowed for a noninferiority HR margin of 1.15, 6-month trastuzumab was not

significantly inferior to 12-month trastuzum-ab [HR=1.28; p=0.29],” said Professor Xavier Pivot, of the Université de Franche Comté, France. “Nevertheless, there is a trend in favor of 12 months treatment for the overall population.”

Further data exploration in selected sub-groups is ongoing, and the results will be presented in December. “The researchers will probably need to look at subsets of patients to see who benefits from 6 months of treatment and who should get a full year,” he suggested.

Advances in breast cancer treatment have made breast-conserving sur-gery feasible for many patients, but

its rates in clinical practice remain low. As such, experts are urging surgeons and on-cologists to implement this approach so more women can conserve their breasts following surgery.

Dr. Carmen Criscitiello from the European Institute of Oncology in Milan, Italy and col-leagues analyzed the different factors that may have affected the choice of surgery of-fered to patients in the NeoALTTO (Neoad-juvant Lapatinib and/or Trastuzumab Treat-ment Optimization) trial. The original trial showed that neoadjuvant treatment combin-ing paclitaxel, lapatinib and trastuzumab sig-nificantly increased the rate of tumor eradica-tion vs paclitaxel combined with either drug alone. [Lancet 2012;379:633-640]

“The experimental treatment with pacli-

taxel plus lapatinib and trastuzumab nearly doubled the rate of pathological complete response. However, this successful result did not translate into a higher rate of breast-con-serving surgery,” said Criscitiello.

Despite the improved response, the pro-portion of women receiving breast-conserv-

Call for action to increase use of breast-conserving surgery

Conference CoverageNov-Dec 2012 10ing surgery remained at around 40 percent, regardless of which treatment the 429 women in the study received.

The researchers found that baseline tumor characteristics prior to neoadjuvant therapy play a major role in deciding the type of sur-gery, irrespective of the response to given therapies and the treatment arm. The baseline factors affecting choice of surgery included tumor multifocality, type of planned surgery at diagnosis, and receptor status, whereby patients with estrogen receptor (ER)-negative tumors were less likely to receive breast-con-serving surgery. [Abstract O247_PR]

“This study highlights a negative attitude that may deny a large fraction of women the chance of preserving their breast, with no clinical reasons to justify this decision. One of the goals of neoadjuvant therapy is increasing the rate of breast conservation, but this goal is clearly not achieved if the type of surgery is chosen according to baseline characteristics,” she argued.

Criscitiello and other experts call for a clear consensus on the use of breast-conserving surgery for patients responding to neoadju-vant therapy. “This will translate the progress in neoadjuvant therapies into higher rates of breast conservation,” she noted.

The SECRAB (Sequencing of Chemothera-py and Radiotherapy in Adjuvant Breast Can-cer) study, which aimed to assess breast cos-

mesis, found that treating women with early breast cancer with synchronous chemoradia-tion reduced the risk of recurrence vs sequen-tial treatment, without a negative impact on breast appearance.

Researchers from University Hospitals Birm-ingham NHS Foundation Trust, UK, took breast photographs of 301 women who underwent breast surgery and evaluated their perceptions before surgery and at 1, 2 and 5 years after surgery. The women included were a subset of patients from a trial that ran-domized 2,296 women to either sequential or synchronous chemoradiation.

“There was no significant difference in cos-mesis or telangiectasia between the two arms as assessed by independent photographic re-view. There was no difference in patient per-ception of breast appearance,” reported Dr. Indrajit Fernando. [Abstract PD253_PR]

Commenting on the studies, Professor Mi-chael Gnant from the Medical University in Vienna, Austria agreed that a more proactive approach to breast conservation should be used. “Modern breast cancer surgery should orientate its strategy according to the post-treatment outcome rather than the baseline situation,” he said. “The other report also adds important information on postsurgical adjuvant therapy. Concomitant chemo-radi-ation is apparently beneficial without addi-tional harm to breast appearance.”

Conference CoverageNov-Dec 2012 11European Society of Medical Oncology (ESMO) 2012 Congress, 28 September-2 October 2012, Vienna, Austria – Naomi Rodrig reports

Sorafenib in NSCLC: Survival benefit in EGFR-mutant tumors?

Treatment with sorafenib as a third- or fourth-line therapy did not improve overall survival (OS) among patients

with advanced non-small cell lung cancer (NSCLC), according to data from the phase III MISSION (Monotherapy Administration of Sorafenib in Patients with Non-Small Cell Lung Cancer) trial. However, a post-hoc bio-marker analysis suggests that patients with EGFR-mutant tumors may benefit. [Abstract 33LBA_PR]

In the trial, 703 NSCLC patients were random-ized to third- or fourth-line monotherapy with oral sorafenib 400 mg twice daily or placebo.

“Median OS, the study’s primary end-point, was similar in the two groups [248 vs 253 days; hazard ratio [HR], 0.99; p=0.4687],” reported lead study investigator, Dr. Louis Paz-Ares from Virgen del Rocio University Hospital in Seville, Spain.

However, median progression-free surviv-al (PFS), time to disease progression, overall response rate, and disease control rate were significantly greater in the sorafenib group (all p<0.001). “One cannot exclude a potential OS benefit in some patient populations,” he said.

Indeed, Professor Tony Mok of the Chi-nese University of Hong Kong reported data from an exploratory analysis suggesting that

sorafenib may improve OS in patients with EGFR mutations. [Abstract 9LBA_PR]

The analysis was conducted using tumor and/or plasma mutation data from 347 pa-tients who participated in the MISSION trial. EGFR and KRAS mutations were detected in 26 and 20 percent of patients, respectively.

Among patients with EGFR-mutant tu-mors, median OS was two times longer in those receiving sorafenib than in placebo-treated patients (420 vs 200 days). In patients with wild-type (WT) EGFR, there was no sig-nificant OS difference between the sorafenib and placebo groups. A similar interaction was demonstrated between EGFR mutation status and the effect of sorafenib on PFS.

“Unlike in patients with WT EGFR tu-mors, those with mutated EGFR treated with sorafenib had better outcomes than placebo-treated patients,” noted Mok. “Contrary to prior suggestions, KRAS was not a predictive biomarker for sorafenib efficacy.”

“The key is the positive interaction analy-sis, which is essential to validate the predic-tive value of a biomarker. The better OS could be partly influenced by the higher number of patients receiving EGFR tyrosine kinase inhibitors [TKIs] after the study, but the im-provement in PFS is mostly attributed to the use of sorafenib,” he suggested.

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Conference CoverageNov-Dec 2012 12

With a growing body of evidence sug-gesting that aspirin may reduce an individual’s chances of developing

colorectal cancer and perhaps other malignan-cies, a “Controversy Session” debate focused on whether that evidence is strong enough to recommend prescribing it to millions of healthy people.

“The efficacy of aspirin in preventing colorectal cancer has been made obvious by more than twenty years of research,” said Professor Robert Benamouzig from Avicenne Hospital, Bobigny, France, who argued in fa-vor of using aspirin for chemoprevention of colorectal adenoma/cancer.

“In 2010, researchers published the 20-year follow-up of five pooled randomized trials that assessed the effect of aspirin on colorectal cancer incidence and mortality. The study of more than 14,000 patients found that daily aspirin at any dose reduced the risk of colorectal cancer by 24 percent and as-sociated deaths by 35 percent after a delay of about 8 to 10 years,” he said.

“The reduction of colorectal cancer rates was in essence a side effect of treatment, as none of these trials had such a reduction as their primary outcome,” he noted. “Nev-ertheless, the evidence that aspirin is effec-

tive for preventing colorectal cancers is very strong.”

Arguing that aspirin is not the answer to colorectal cancer prevention, Professor Nadir Arber of the Sourasky Medical Center in Tel Aviv, Israel, countered, “NSAIDs and in par-ticular aspirin are very promising in second-ary prevention of colorectal neoplasia; how-ever, their role in primary prevention is still not proven.”

He suggested that the majority of the population is not going to benefit from aspi-rin use. “Having said that, specific high-risk populations definitely can benefit from as-pirin intake, including people with heredi-tary non-polyposis colorectal cancer, familial adenomatous polyposis, existing colorectal cancer or adenoma,” he said.

Arber also presented preliminary data showing how the efficacy and toxicity of as-pirin in preventing cancer can be predicted based on certain single nucleotide polymor-phisms. “In the future, based on genomic profile, we would be able to identify people who are at high risk of developing colorec-tal cancers and who might benefit from aspirin therapy without developing side ef-fects, such as gastrointestinal bleeding or in-tracranial hemorrhage,” he predicted.

European Society of Medical Oncology (ESMO) 2012 Congress, 28 September-2 October 2012, Vienna, Austria – Naomi Rodrig reports

Aspirin for cancer prevention: Jury still out

Case StudyNov-Dec 2012 13

Capecitabine in advanced gastric cancer

Dr. Kam-Tong YuenAssociate Consultant Department of Oncology Princess Margaret HospitalHong Kong

Presentation and diagnosisA 62-year-old man with a history of Heli-

cobacter pylori-related peptic ulcer and gastro-esophageal reflux with Barrett’s oesophagus presented with persistent epigastric pain for 1 week in January 2012.

He was hospitalized in a public hospital. Complete blood picture showed a hemoglo-bin level of 11 g/dL vs 14.2 g/dL in December 2011. Physical examination did not reveal any abnormality. Esophagogastro-duodenoscopy showed an ulcer at the cardia, confirmed as adenocarcinoma on biopsy.

ManagementThe patient consulted a private oncologist.

Contrast CT scan of abdomen in January 2012 showed marked thickening of the gastric wall, compatible with tumor infiltration. There was extra-gastric spread to perigastric soft tissue and omentum, as well as lymphadenopathy and moderate ascites. There were multiple metastat-ic nodules in the liver, located in anterior aspect of segment II, segment V adjacent to the gall-bladder fossa, and in segment VI (largest, 2 cm).

The patient had received four cycles of che-motherapy at the private clinic, consisting of bi-weekly docetaxel, oxaliplatin and capecitabine. An FDG PET-CT in March 2012 showed gastric wall thickening similar to that in the previous CT scan in January 2012, but not hypermeta-bolic (SUVmax, 2.4). The liver metastases were also noted but were not hypermetabolic, and the ascites had resolved completely. No perigastric lymphadenopathy or soft tissue density was demonstrated. However, the radiologist com-

mented that liver metastases could have similar activity to the background tissue and could not be excluded.

The patient consulted us in mid-March 2012, and was switched to chemotherapy with XELOX (oxaliplatin and capecitabine). Capecitabine dose was reduced to 75 per-cent due to suboptimal creatinine clearance. Eight cycles of chemotherapy were given from March to August 2012, which were well tolerated with no delay due to marrow sup-pression. The maximal grade of hand-foot syndrome was I; he also developed grade II peripheral neuropathy due to oxaliplatin from cycle seven onward.

Contrast CT after the fifth cycle of XE-LOX showed decreased gastric wall thicken-ing. Soft tissue nodules were seen at the area posterior-inferior to gastric fundus (size up to 2.1 cm), suggestive of extra-gastric spread. Gastric and perigastric spread decreased as compared with previous CT. Small hy-podense lesions were seen in the liver (largest, 6 mm at segment V/VI). Soft tissue infiltrate in the omentum had resolved. Several soft tis-sue nodules (up to 1.3 cm) were seen in the omentum at right anterior abdomen. There was partial regression of peritoneal deposit, omental and hepatic metastases.

The patient was last seen in September 2012, complaining of occasional abdominal discomfort and persistent residual pares-thesia affecting his hands and soles, which caused difficulty in daily activities. He is cur-rently on vitamin B6 50 mg twice daily.

DiscussionAdvanced metastatic gastric can-

cer carries poor prognosis (5-year survival rate, 10-15 percent). Combination chemo-therapy improves survival vs best supportive

Case StudyNov-Dec 2012 14

Before chemotherapy

Metastasis in segment V of right lobe Metastasis resolved

After chemotherapy

Liver

Peritoneum

References: 1. N Eng J Med 2008;358:36-46. 2. Br J Cancer 2006;94:956-963. 3. Am J Clin Oncol 2009;32:559-563.

care. The ECF regimen (epirubicin, cisplatin and infusional fluorouracil) had been widely used until a few years ago. However, infu-sional fluorouracil is rather inconvenient, while cisplatin causes renal toxicity, hearing loss, emesis and peripheral neuropathy. It also re-quires an intensive hydration scheme. Data from the REAL-2 (Randomized ECF for Ad-vanced and Locally Advanced Esophagogas-tric Cancer) trial showed that capecitabine and oxaliplatin are as effective as fluorouracil and cisplatin.1 Currently, there is a trend to replace the tedious ECF scheme by EOX (epirubicin, oxaliplatin and capecitabine).

Capecitabine is generally well tolerated, and hand-foot syndrome is manageable. In this case, when we took over patient man-agement, he had already been treated with docetaxel, oxaliplatin and capecitabine. His renal function was suboptimal, requiring dose reduction of capecitabine. Hence, we decided to withdraw epirubicin, based on

the fact that a number of separate phase II trials using XELOX demonstrated compa-rable disease control (overall response rate, 51.2-65 percent) and survival data (median progression-free survival, 5.6-7.5 months; overall survival, 9.8 months) to EOX (the cor-responding figures are 47.9 percent, 7 months and 11.2 months), although there is no direct comparison in a randomized trial.1-3 The XE-LOX regimen is also more tolerable.

Another issue was analyzing the interim PET-CT result. Since no intravenous CT con-trast was given, the metastatic lesions might not have shown up, as the sensitivity of FDG uptake for certain subtypes of gastric can-cer is low. There was no baseline PET-CT for comparison as well; hence, the result of interim PET-CT, especially the liver metasta-ses status, should not be overemphasized.

Peritoneal metastases Residual metastasis

Case StudyNov-Dec 2012 15

Capecitabine treatment in metastatic breast cancer

Dr. Roland LeungMedical OncologistDepartment of MedicineQueen Mary HospitalHong Kong

Dr. Thomas YauClinical Assistant Professor in Medical OncologyDepartments of Medicine and SurgeryUniversity of Hong Kong

Presentation and treatmentA 75-year-old woman with known bronchi-

ectasis and hypertension was referred to our hospital for management of metastatic breast cancer in 2011. Her family history of cancer was remarkable as her father had laryngeal cancer, brother had tongue cancer, and an aunt was diagnosed with breast cancer in her 50s.

The patient presented with a self-palpated left breast mass in July 2008. Fine needle aspi-ration cytology (FNAC) confirmed intraduct-al carcinoma in the left breast. Subsequent mammogram and ultrasound scan showed an approximately 3-cm lesion.

Left mastectomy with sentinel lymph node biopsy was performed in September

2008. Histology showed invasive ductal car-cinoma not otherwise specified, with clear resection margins. The invasive component measured 8 mm, which was a pT1b tumor, and was classified as grade II (modified Bloom–Richardson). Lymphovascular per- meation was suspected, and neither of the two sentinel lymph nodes removed were positive. Immunohistochemical staining for estrogen receptor (ER), progesterone receptor (PR) and HER2 oncoprotein was negative (ie, triple negativity). No adjuvant treatment was therefore indicated.

A 4-mm nodule in left chest wall was noted in May 2009. Excisional biopsy was performed in September 2009 after it incr-eased in size to 8 mm. Histology revealed carcinoma con-sistent with breast primary. Tumor markers were normal. Adjuvant radiation therapy to chest wall was completed in February 2010.

The patient then noted a left axillary nod-ule in April 2011, and FNAC confirmed ad-enocarcinoma. PET-CT scan showed multiple regional lymph node metastases and suspi-cious pleural deposit at the left upper lobe of the lung. (Figure 1) Baseline blood test results, including tumor markers, were normal.

Figure 1. Pretreatment PET-CT scan in (April 2011)Metastatic L axillary LN and the unrelated mediastinal LN (background bronchiectasis)

Pleural metastasis seen on PET and fusion

Case StudyNov-Dec 2012 16

Treatment with single-agent capecitabine 900 mg/m2 orally BID was started in Au-gust 2011 on a 2-week on/1-week off sched-ule. PET-CT reassessment in October 2011 showed interval decrease in size and metabol-ic activity of the metastatic lymph nodes and resolved pleural deposit, suggesting partial response to treatment. (Figure 2) The latest PET-CT scan in May 2012 indicated further decline in metabolic activity of the metastatic lymph nodes. The patient is currently still on capecitabine therapy.

DiscussionMetastatic breast cancer consists of a wide-

spectrum of disease with survival ranging from months in the case of inflammatory breast cancer to many years or even decades for slowly progressive hormone receptor-pos-itive breast cancer. Triple-negative metastatic breast cancer poses a particularly difficult challenge for oncologists due to the limited number of active agents that can be used. Currently, only conventional chemotherapy agents are approved for metastatic triple-negative breast cancer. Despite early promise, anti-angiogenic agents and poly (ADP-ribose) polymerase (PARP) inhibitors are still under-going clinical investigation for triple-negative cancers.

The treatment of elderly patients who are otherwise fit and active is a growing challenge

for oncologists. As the population ages and their general health improves, the number of deaths attributed to breast cancer is actually on the rise according to the latest cancer reg-istry data.1

Preserving functionality, minimizing side effects, and achieving satisfactory disease control are of equal importance in treat-ing this group of patients. Due to the intrin-sic precarious balance between health and disease in the elderly, special consideration is required when choosing chemotherapy. Agents given in a metronomic fashion are bet-ter tolerated in this group. Infusional chemo-therapy provides good compliance, but frail patients may end up with hospitalization and other side effects (eg, infections and organ failure) if tolerance to intravenous chemo-therapy is poor. These severe adverse events often spell the end of active chemotherapy for this group of patients. Oral metronomic ther-apy has the advantage of giving low doses of therapy for a long period of time; if adverse events occur, patients can stop the chemother-apy and avoid severe adverse events.

Capecitabine is particularly useful because pills in different dosages are available for easy dose adjustment and fine tuning, ensuring a good balance between tolerability and efficacy.

Reference:1.Hong Kong Cancer Registry. http://www3. ha.org.hk/cancereg/e_a1a.asp.

Figure 2. Reassessment PET-CT scan (October 2011) showed partial response to treatment

NewsNov-Dec 2012 17

Are colonoscopy factors affecting colon cancer risk?

Rajesh Kumar

Colonoscopy-related factors were more important than the characteristics of detected polyps for stratification of

colorectal cancer risk in a population-based case-control study in Germany.

Poor bowel preparation, incomplete remov-al of all polyps and no surveillance colonos-copy within 5 years of the first polyp detection were the main colonoscopy-related factors, while polyp characteristics included a size of ≥1 cm, villous components or high-grade dys-plasia, detection of 3 or more polyps, and ≥1 proximal polyp. [Ann Intern Med 2012;4:225-232]

Researchers compared the role of these factors in 3,148 case subjects and 3,274 con-trols. Both case and control participants had physician-validated detection of pol-yps (other than hyperplastic polyps). A total of 155 cases and 260 controls with physician-validated polyp detection in the past 10 years were identified for further analysis.

The following characteristics were signifi-cantly more common among case participants than among control participants: not all pol-yps completely removed (29.0 vs 9.6 percent; OR, 3.73), no surveillance colonoscopy within 5 years (26.5 vs 11.5 percent; OR, 2.96), and detection of ≥3 polyps (14.2 vs 7.3 percent; OR, 2.21). Overall, 41.1 percent of cancer cases were statistically attributable to colonosco-py-related factors and 21.7 percent to polyp

characteristics. “This research should have been summa-

rized as ‘suboptimal colonoscopy surveillance leads to false sense of security in colorectal cancer prevention’,” commented Dr. Lim Jit Fong, a colorectal surgeon at Fortis Colorectal Hospital, Singapore.

In fact, patients with low-risk premalig-nant polyps should have repeat colonoscopy in 3 years and patients with high-risk polyps in 1 year. “Therefore, the researchers’ timeline of 5 years after polyp removal is already too long,” he said, quoting the American Society of Gastrointestinal Endoscopy guidelines.

He added that many patients ended up de-veloping colorectal cancer, as expected, during the interval.

“The [study’s] take-home point is that a procedure should only be called a good colonoscopy if there was complete intubation from anus to caecum, with good clean colon, careful assessment of colon on the way out as well as adequate counseling of patients before and after colonoscopy regarding the purpose and limitations of the procedure,” Lim opined. “That still does not mean that colonoscopy factors are more important than the polyp characteristics.”

Earlier studies have found the character-istics of adenomas detected on colonoscopy to be predictive of adenoma recurrence. The researchers conceded that the current study was limited due to its observational nature, with potential for residual confounding and selection bias.

NewsNov-Dec 2012 18

Anti-HER2 breast cancer therapy useful for brain metastases

Rajesh Kumar

I n human epidermal growth factor receptor 2 (HER2)-positive breast cancer

patients, treatment with the anti-HER2 agent trastuzumab before brain metastasis (BM) occurs is associated with significantly longer time to BM development, according to an Asian retrospective study led by researchers from the National Cancer Center, Singapore. In cases where BM had already been detected, trastuzumab administered along with lapatinib offered a survival benefit. [BJC 2012; DOI:10.1038/bjc.2012.346]

Currently, there is limited usage of anti-HER2 treatment after detection of brain metastases in Asian patients. However, the research findings highlight the need for new therapeutic approaches to effec-tively prevent or treat brain metastases in HER2-positive breast cancer patients, the investigators said.

They analyzed data from 280 HER2-positive breast cancer patients diagnosed with BM from January 2006 to December 2008 in Singapore, Malaysia, Indonesia, Thailand, Korea and the Philip-pines. The data included demographics, tumor characteristics, treatment details, and events dates.

Before BM diagnosis, 63 percent received anti-HER2 treatment. These patients had significantly longer time to BM develop-ment than those without anti-HER2 treat-ment (median, 33 vs 19 months; p≤0.002).

After BM was detected, 93 percent received radiotherapy, 57 percent received chemo-therapy, and 41 percent received anti-HER2 treatment with trastuzumab and/or lapatinib.

Use of both anti-HER2 agents sequen-tially in patients with BM demonstrated the longest survival and was associated with a significant survival benefit over no anti-HER2 treatment (median 26 vs 6 months; HR, 0.37).

In Asia, anti-HER2 treatment is not uniformly utilized, ranging from 63 percent before BM to only 41 percent after BM. A quarter of the patients never received anti-HER2 treatment. This is in contrast to the trend in Western countries where there is no drop in anti-HER2 treatment utiliza-tion after BM, said the researchers, quoting earlier studies.

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Brain metastases from primary breast cancer

NewsNov-Dec 2012 19

That was the common reaction to many presentations at the recent ESMO 2012

Congress in Vienna, including the majority of ‘late breakers’ presented at the presiden-tial sessions. Yes, negative results must be reported, but is the latest trend indicating a slowdown in cancer research breakthroughs, restricting the development of new medica-tions?

Study authors and commentators tried to put a positive spin on the disap-pointing data, claiming that ‘more research is needed’ or ‘further mutation analysis may reveal a subgroup of patients who can benefit’.

That may be true, but many experts are now calling for a paradigm change in cancer trials, moving towards personalized medicine. Rather than randomly assigning patients to a particular treatment regimen, a personalized medicine approach calls for selecting study drugs based on prior identi-fication of the underlying mutations in a patient’s tumor.

With limited knowledge of cancer genetics, this approach may only be appli-cable to a few cancer types, but might never-theless speed up the discovery and approval of new cancer drugs.

The Editor

Another negative study…

“[This] may be largely related to the high costs associated with anti-HER2 treatment, especially in countries with no reimbursement. Further, discontinuation of anti-HER2 treat-ment upon the development of resistance to

prior trastuzumab and lapatinib treatment may partly explain the decline in use,” they hypoth-esized, suggesting that more clinical trials are needed to determine the optimal regimen of anti-HER2 treatment.

NewsNov-Dec 2012 20

HK researchers pioneer computer-assisted surgery for bone tumorsChristina Lau

Surgeons at the Department of Orthope-dics and Traumatology, Chinese Uni-versity of Hong Kong (CUHK) have re-

ported positive results of computer-assisted tumor surgery (CATS) that overcomes the disadvantages and limitations of convention-al bone tumor surgery.

The technique involves fusion of preopera-tive CT and MRI images, followed by recon-struction of two- or three-dimensional images that were used to plan bone resection. Ac-cording to the researchers, CATS is particular-ly useful in complicated bone tumor surgery, such as pelvic or sacral tumors and pediatric bone cancers.

“With the conventional approach of bone tumor surgery, preoperative two-dimensional images are integrated to simulate a three-di-mensional surgical plan. Surgeons often have difficulties in accurately executing the virtual surgical plan,” said Dr. Kwok-Chuen Wong. “Inaccurate resection may lead to local tumor recurrence and death. Furthermore, surgeons often have to remove normal bone tissues and surrounding structures, which will lead to impairment of limb function.”

In contrast, CATS allows detailed analysis of the patient’s anatomy and tumor position, enabling precise virtual surgical simulation and resection planning. “The surgical plan can be executed with the assistance of a computer navigation system to achieve a high level of ac-curacy and precision, ensuring clear resection margins and reducing the error in bone resec-tion to <2 mm,” explained Wong. “It helps in-crease the chance of total tumor resection, and preserve normal bone tissues and joints.”

The orthopedic surgery team at CUHK has started developing and refining the technique since 2006. A total of 32 patients with malignant bone tumors have been successfully treated so far. The results were published in international journals.

In a study of 20 patients (mean age, 31 years), histological examination of all CATS-resected specimens showed a clear tumor margin. The achieved bone resection matched the planned resection with a difference of ≤2 mm. The achieved positions of custom pros-theses were comparable to the planned posi-tions when postoperative and preoperative CT images were merged in five cases. The mean Musculoskeletal Tumor Society (MSTS) score – a measure of function – was 28. [Clin Orthop Relat Res 2012; e-pub Sep 5]

In selected patients with bone sarcomas of extremities (n=8), CATS achieved accu-rate resection with a difference of ≤2 mm in any dimension compared with that planned in patients with custom prostheses. No local recurrence was reported, and the mean MSTS score was 29. [Clin Orthop Relat Res 2012; e-pub Sep 5]

The CUHK researchers will further devel-op the technique and explore other possibili-ties, such as the use of patient-specific tumor cutting templates.

From left: Prof. Shekhar Madhukar Kumta, Dr. Wong

NewsNov-Dec 2012 21

Unique pattern of BRCA mutations in Hong Kong

Christina Lau

Data of 535 patients with breast or ovarian cancer who received BRCA mutation testing through the Hong

Kong Hereditary Breast Cancer Family Reg-istry have revealed a unique pattern of BRCA mutations among local patients.

The data, presented on the occasion of Breast Cancer Awareness Month in October, showed that BRCA2 mutations are more com-mon in Hong Kong than in the West. In ad-dition, a number of new mutation sites were found on the BRCA gene.

“This is the first report on Chinese pa-tients, and will likely lead to further research to change future methods of genetic testing to make it more accessible,” said Dr. Ava Kwong, Chairman of the Registry.

In the cohort, a BRCA mutation was found in 10.5 percent of patients (n=56), a rate compa-rable to Western studies. However, 51.8 percent of local BRCA mutation carriers had BRCA2 mutations, whereas in the West BRCA1 muta-tions are the majority (>80 percent).

“Forty-two percent of the BRCA muta-tions found in Hong Kong have never been reported elsewhere in the world,” pointed out Kwong. “We also identified a total of four founder mutations.”

Founder mutation refers to the loss of ge-netic variation that occurs when a new popu-lation is established by a very small number of individuals from a larger population. In the Hong Kong Registry, 80 percent of patients were originally from Guangzhou, China.

“These four founder mutations were re-peatedly seen when a BRCA mutation was identified in our cohort, and accounted for 23 percent of all the BRCA mutations,” she continued. “This is important because in populations with founder mutations, we could screen the founder mutations first be-fore screening the full BRCA1 and BRCA2 genes. The full screening takes a longer time and is more expensive. Therefore, finding these four founder mutations now is very important; if we can confirm that they are Chinese specific, it will change the method of genetic screening in Chinese individuals, making it more accessible. Further studies are being performed to confirm these muta-tions and their effect in Chinese individuals in other countries.”

According to the Registry data, the aver-age age of women referred for genetic coun-seling and testing was 43 years. However, 36.7 percent of them were younger than 40. “Patients diagnosed at a young age were found to have multiple family members with breast, ovarian, prostate and BRCA-related cancers,” said Kwong. “We also tested 164 family members of the 56 BRCA mutation carriers. More than half [51.8 percent; n=85] of them tested positive, and this included individuals with or without cancer.”

In addition, 36 male breast cancer pa-tients were tested for BRCA mutation. Seven of them (19.4 percent) were found to carry a BRCA mutation, all of which were BRCA2 mutations. One of the carriers also had prostate cancer.

NewsNov-Dec 2012 22

Melanoma risk independent of UV radiation in some redheads

Christina Lau

In people with red hair and fair skin, the well-established risk of melanoma may be caused by more than just a lack of natural

protection against ultraviolet (UV) radiation, according to a preclinical study that identified a UV-independent pathway of melanoma carci-nogenesis controlled by the skin pigment itself.

“We’ve known for a long time that people with red hair and fair skin have the highest melanoma risk of any skin type. Our study suggests that pheomelanin, the predominant melanin in these individuals, may itself con-tribute to the development of melanoma,” said senior author Dr. David Fisher of the Mas-sachusetts General Hospital in Boston, USA. [Nature e-pub 31 October 2012; doi:10.1038/nature11624]

“Our finding does not change the mela-noma risk of people with this skin type, but identifies a new mechanism to help explain it,” he continued. “This may provide an op-portunity to develop better sunscreens and other measures that directly address this pigm-entation-associated risk while continu-ing to protect against UV radiation, which remains our first line of defense against mela-noma and other skin cancers.”

Pheomelanin is known to be less effective than eumelanin (found in dark brown or black skin) in shielding against UV damage. However, the incidence of melanoma in red-haired, fair-skinned individuals may not be fully explained by limited UV protection. For example, mela-noma is not restricted to sun-exposed skin, and studies have suggested that sunscreens may not be as effective in protecting against melanoma vs other types of skin cancers.

In their study, Fisher and colleagues used mice that were nearly identical genetically except for the gene that controls the type of melanin produced. They activated the mela-noma-associated form of the BRAF oncogene in patches of the animals’ skin pigment cells. Within months, melanoma developed in half of the mice with a phenotype analogous to red-haired/fair-skinned humans, compared with only a few dark mice. This occurred without additional environmental stress such as gene aberrations or UV exposure.

The researchers then investigated the mech-anism of UV-independent carcinogenesis in a group of red-haired/fair-skinned mice in which all pigment production was genetically dis-abled (albino redheads). Results showed that selective absence of pheomelanin synthesis was protective against melanoma development.

“This indicates that something about the pigment itself was leading to melanoma. This pigmentation-associated risk may be chemical-ly related to the generation of reactive oxygen species [ROS], which can damage cells,” sug-gested Fisher. “In fact, we discovered elevated levels of a type of DNA damage typically pro-duced by ROS in the skin of red mice, but not in albino redheads. This supports oxidative damage as a mechanism behind red pigment-associated melanoma formation.”

“While antioxidant treatments may be able to reduce this risk, further research is needed to identify safe and effective ways to exploit this knowledge, as antioxidant treatments have been seen in some instances to increase rather than prevent oxidative damage,” he cautioned. “We also need to investigate whether the find-ings may pertain to people with, for example, fair skin and dark hair.”

NewsNov-Dec 2012 23

Repeat surgeries for glioblastoma may prolong survival

Naomi Rodrig

Patients who undergo repeated surger-ies to remove glioblastomas may sur-vive longer than those who have just

one operation, according to new research from the Johns Hopkins University School of Medicine, Baltimore, USA. [Journal of Neuro-surgery 2012; DOI: 10.3171/2012.9.JNS1277]

Glioblastoma inevitably recurs after resection, chemotherapy, and/or radiation. The median survival time after diagnosis is only 14 months. With recurrence a near certainty, many have questioned the value of performing additional operations, especially given the dangers of brain surgery such as neurological injury or death.

“We are reluctant to operate on patients with brain cancer multiple times as we are afraid to incur new neurological deficits, or pessimistic about their survival chances,” said lead study investigator, Professor Alfredo Quinones-Hinojosa. “But this study tells us that the more we operate, the longer they may survive. We should not give up on these patients.”

He and his team reviewed the records of 578 patients who underwent surgery to remove a glioblastoma between 1997 and 2007. At the last follow-up, 354 patients had one surgery, 168 had two resections, and 41 and 15 patients had three and four opera-tions, respectively. The median survival for patients who underwent one, two, three and four operations was 6.8 months, 15.5 months, 22.4 months and 26.6 months, respectively.

He cautioned that this analysis may overes-

timate the value of multiple surgeries, as it is possible that patients who did better had tumor biology that predisposed them to live longer.

“The only thing that has been proven to work for glioblastoma is surgery,” noted Quinones-Hinojosa. “Without surgery, these patients don’t have much of a chance.” However, glioblastomas are deeply entan-gled in healthy brain tissue, which makes them notoriously difficult to eradicate with surgery alone. Along with reducing tumor size, repeated surgeries may also increase the efficacy of radiation and chemotherapy.

Quinones-Hinojosa noted that with each successive surgery, the procedure itself becomes more technically challenging due to anatomy changes, damaged blood vessels and frail tissues. “The procedure should only be done when it’s relatively safe, and in patients who can tolerate anesthesia and the long recovery period,” he suggested.

NewsNov-Dec 2012 24

Radiotherapy after prostatectomy: Limited PFS benefit

Naomi Rodrig

Long-term data from the European Organization for Research and Treat-ment of Cancer (EORTC) trial 22911

showed that immediate postoperative irradi-ation for high-risk prostate cancer signifi-cantly improves biochemical progression-free survival (PFS) and local control compared with a wait-and-see policy, supporting results of the 5-year follow-up analysis; however, improvements in clinical PFS were not maintained. [Lancet 2012; DOI:10.1016/S0140-6736(12)61253-7]

The randomized phase III trial recruited patients aged ≤75 years with untreated patho-logic T2-3 prostate cancer from 37 institutions across Europe. Eligible patients had one or more pathological risk factors, including extra-capsular extension, positive surgical margins, and seminal vesicle invasion.

Patients were randomly assigned centrally to postoperative irradiation (60 Gy of conven-tional irradiation to the surgical bed for 6 weeks) (n=502) or to a wait-and-see policy (n=503) until biochemical progression (increase in prostate-specific antigen [PSA] >0.2 μg/L confirmed twice at least 2 weeks apart). Patients were followed up for a median of 10.6 years (range, 2 months

to 16.6 years).The investigators analyzed the primary

endpoint, biochemical PFS, by intention to treat and did exploratory analyses of hetero-geneity of the effect.

Postoperative irradiation significantly improved biochemical PFS compared with wait-and-see policy. In total, 39.4 percent of patients in the irradiation group and 61.8 percent of those in the wait-and-see group had biochemical or clinical progression or died (hazard ratio [HR], 0.49; p<0.0001).

Late adverse effects of any type and grade were more frequent in the postoperative irradiation group than in the wait-and-see group (10-year cumulative incidence, 70.8 vs 59.7 percent; p=0.001).

Unlike in the 2005 analysis, which demonstrated improvements in both clinical and biochemical PFS at 5 years, the clinical PFS benefits of radiation were not sustained in the long term. [Lancet 2005;366: 572-578]

Exploratory analyses suggest that postop-erative irradiation might improve clinical PFS in patients younger than 70 years and in those with positive surgical margins, but could have a detrimental effect in patients aged 70 years or older.

READ JPOG ANYTIME, ANYWHERE. Download the digital edition today at www.jpog.com

NewsNov-Dec 2012 25

Overweight breast cancer patients more likely to relapse

Rajesh Kumar

Women who are obese or overweight at diagnosis of estrogen receptor

(ER)-positive breast cancer face a 30 percent higher risk of relapse even if they receive the best available treatment, according to a recent study.

Such patients are already known to be at an increased risk of dying prematurely. The current study suggests that extra body fat causes hormonal changes and inflammation that may drive some cases of breast cancer to spread and recur despite treatment. [Cancer 2012; DOI: 10.1002/cncr.27527]

“Other studies have shown that weight reduction after a breast cancer diagnosis lowers the risk of recurrence. The findings from this study suggest that women who are obese and have ER-positive tumors are most likely to benefit from weight reduc-tion,” said lead author Dr. Joseph Sparano of the Albert Einstein College of Medicine

in New York, USA.The investigators compared the health

outcomes of 4,770 normal-weight, obese and overweight patients with stage I-III breast cancer who had participated in three treat-ment trials. The trials’ inclusion criteria required participants to have normal heart, kidney, liver, and bone marrow function, thereby excluding patients with other signifi-cant health issues. As a result, the researchers were able to single out the influence of obesity from other factors affecting cancer recurrence and survival.

Obesity was associated with inferior disease-free survival (p=0.0008) and overall survival (p=0.002) in hormone receptor-positive disease, but not in other subtypes. This was despite optimal treatment including chemotherapy and hormonal therapy.

“Treatment strategies aimed at interfering with hormonal changes and inflammation caused by obesity may help reduce the risk of recurrence,” suggested Sparano.

Market WatchNov-Dec 2012 26

ZYTIGA®(abiraterone acetate)ORAL, ONCE-DAILY DOSING

ZYTIGA® is indicated with prednisone or prednisolone for the treatment of metastatic castration-resistant prostate cancer in adult men whose disease has progressed on or after a docetax-el-based chemotherapy regimen.1

Mechanism of action• Abiraterone is an androgen biosynthesis inhibitor (ABI) that

directly affects the androgen signaling pathway by inhibiting CYP17 (17a-hydroxylase/C17, 20-lyase), an enzyme complex needed for androgen biosynthesis.

Efficacy• Zytiga® + prednisone showed a statistically significant improvement in overall survival.2,3

Safety• Established safety profile; the most common adverse reactions (≥ 5%) reported in clinical

trials were joint swelling or discomfort, hypokalemia, edema, muscle discomfort, hot flushes, diarrhea, urinary tract infection, cough, hypertension, arrhythmia, urinary frequency, nocturia, dyspepsia, and upper respiratory tract infection.

References:1. Zytiga Package Insert (Hong Kong). 2. N Eng J Med 2011;364:1995-2005. 3. Fizazi K et al. Presented at The European Multidisciplinary Cancer Congress 2011, abstract#7000.

Oral, once-daily dosing

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CalendarNov-Dec 2012 2817th Connective Tissue Oncology Society Annual Meeting14/11/2012 to 17/11/2012Prague, Czech RepublicTel: +001 301 502 7371Fax: +001 703 548 4882E-mail: ctos@ctos.orghttp://www.ctos.org/meeting/2012/index.asp

4th European Multidisciplinary Meeting on Urological Cancers (EMUC 2012)16/11/2012 to 18/11/2012Barcelona, SpainTel: +031 26 389 0680Fax: +031 26 389 0674E-mail: emuc-meeting2012@congressconsultants.comhttp://emucbarcelona2012.org/welcome/welcome/

17th Annual Scientific Symposium of Hong Kong Cancer Institute – Clinical Application of Biomarkers in Cancer Therapy24/11/2012 to 25/11/2012Fax: +852 2632 5816E-mail: conference2012@clo.cuhk.edu.hkhttp://www.clo.cuhk.edu.hk/news.html#Event1

ASCO’s Quality Care Symposium30/11/2012 to 1/12/2012San Diego, USATel: +001 888 282 2552Fax: +001 571 483 1300E-mail: qualitysymposium@asco.orghttp://www.asco.org/ASCOv2/Meetings/ASCO%27s+Quality+Care+Symposium

San Antonio Breast Cancer Symposium (SABCS)4/12/2012 to 8/12/2012San Antonio, USATel: +001 210 450 1550Fax: +001 210 450 1560E-mail: sabcs@uthscsa.eduhttp://www.sabcs.org/index.asp

2012 American Society of Hematology (ASH) Annual Meeting and Exposition8/12/2012 to 11/12/2012Atlanta, USATel: +001 703 449 6418Fax: +001 703 563 2715E-mail: ashregistration@jspargo.comhttp://www.hematology.org/Meetings/Annual-Meeting/Gen-eral/2746.aspx

Tumor Invasion and Metastasis20/1/2013 to 23/1/2013San Diego, USATel: +001 215 440 9300 / 866 423 3965Fax: +001 215 9313E-mail: aacr@aacr.orghttp://www.aacr.org/home/scientists/meetings--workshops/special-conferences/tumor-invasion-and-metastasis.aspx

2013 Gastrointestinal Cancers Symposium – Science and Multidisciplinary Management of GI Malignancies24/1/2013 to 26/1/2013San Francisco, USATel: +001 888 788 1522 / 703 449 6418Fax: +001 703 563 2715 E-mail: giregistration@jspargo.com http://www.gicasym.org/

2013 Genitourinary Cancers Symposium14/2/2012 to 16/2/2012Orlando, USATel: +001 888 788 1522 / 703 449 6418Fax: +001 703 563 2715E-mail: guregistration@jspargo.comhttp://gucasym.org

13th St. Gallen International Breast Cancer Conference 201313/3/2013 to 16/3/2013St. Gallen, SwitzerlandInfo: Q Events AGTel: +041 71 228 58 08Fax: +041 71 228 58 09E-mail: bcc@qevent to s.bizhttp://www.oncoconferences.ch/dynasite.cfm?dsmid=111783

CalendarNov-Dec 2012 291st International Congress on Oncological Perspectives of Fertility Preservation: Gynecological & Breast Cancer21/3/2013 to 23/3/2013Berlin, GermanyTel: +972 3 5666166Fax: +972 3 5666177E-mail: info@comtecmed.comhttp://comtecmed.com/opfp/2013/Default.aspx

EORTC/EANO/ESMO 2013 – Trends in Central Nervous System Malignancies22/3/2013 to 23/3/2013Prague, Czech RepublicTel: +032 2 775 02 01Fax: +032 2 775 02 00E-mail: eortceanoesmo@ecco-org.euhttp://www.ecco-org.eu/Conferences/Conferences/EORTC_EANO_ESMO.aspx

5th IMPAKT Breast Cancer Conference2/5/2013 to 4/5/2013Brussels, BelgiumTel: +041 (0)91 973 19 39Fax: +041 (0)91 973 19 18http://www.esmo.org/events/breast-2013-impakt.html

15th World Congress on Gastrointestinal Cancer3/7/2013 to 6/7/2013Barcelona, SpainTel: +001 678 242 0906Fax: +001 770 751 7334E-mail: registration@imedex.comhttp://worldgicancer.com/WCGI/WGIC2013/index.asp

11th Annual Meeting of the Japanese Society of Medical Oncology29/8/2013 to 31/8/2013Sendai, JapanTel: +081 22 723 3211Fax: +081 22 723 3210E-mail: jsmo2013@congre.co.jphttp://www.congre.co.jp/jsmo2013/english/

Oncology Tribune is published 6 times a year by UBM Medica, a division of United Business Media. Oncology Tribune is a controlled circulation publication to medical practitioners in Asia. It is also available on subscription to members of allied professions. The price per annum is US$48 (surface mail) and US$60 (overseas airmail); back issues at US$5 per copy. Editorial matter published herein has been prepared by professional editorial staff. Views expressed are not necessarily those of UBM Medica. Although great effort has been made in compiling and checking the information given in this publication to ensure that it is accurate, the authors, the publisher and their servants or agents shall not be responsible or in any way liable for the continued currency of the information or for any errors, omissions or inaccuracies in this publication whether arising from negligence or otherwise howsoever, or for any consequences arising therefrom. The inclusion or exclusion of any product does not mean that the publisher advocates or rejects its use either generally or in any particular field or fields. The information contained within should not be relied upon solely for final treatment decisions.

© 2012 UBM Medica. All rights reserved. No part of this publication may be reproduced in any language, stored in or introduced into a retrieval system, or transmitted, in any form or by any means (electronic, mechanical, photocopying, recording or otherwise), without the written consent of the copyright owner. Permission to reprint must be obtained from the publisher. Advertisements are subject to editorial acceptance and have no influence on editorial content or presentation. UBM Medica does not guarantee, directly or indirectly, the quality or efficacy of any product or service described in the advertisements or other material which is commercial in nature. Printed by Fortune Printing International Ltd, 3rd Floor, Chung On Industrial Building, 28 Lee Chung Street, Chai Wan, Hong Kong.

ISSN: 2078-2535Dr. Michael Cheung Ming-Chee (Asia Cancer & Hematology Centre)

Dr. Daniel Chua Tsin-Tien (Hong Kong Sanatorium & Hospital)

Dr. William Foo (Hong Kong Baptist Hospital)

Dr. Carol Kwok (Princess Margaret Hospital)

Dr. Philip Kwok (Queen Elizabeth Hospital)

Dr. Ava Kwong (University of Hong Kong)

Dr. Kwok-Chi Lam (Chinese University of Hong Kong)

Prof. Raymond Liang (Hong Kong Sanatorium & Hospital)

Prof. Hextan Ngan (University of Hong Kong)

Dr. Roberta Pang (University of Hong Kong)

Prof. Ronnie T. P. Poon (University of Hong Kong)

Dr. Wai-Man Sze (Cancer Care Center)

Editorial Advisory Board – Hong Kong

Oncology Tribune contains articles from Cancer Network, under license from UBM Medica LLC. Copyright © 2012 UBM Medica LLC.

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