Pancreatic cancerPancreatic cancerchemotherapychemotherapy

Jarosław Reguła M.D.Jarosław Reguła M.D.

Department of Gastroenterology, Institute of Oncology, Department of Gastroenterology, Institute of Oncology, Warsaw, PolandWarsaw, Poland

Pancreatic cancerPancreatic cancer

• 10-th common cancer10-th common cancer

• 4-th cause of cancer death4-th cause of cancer death

• Overall 5-year survival – ca. 4%Overall 5-year survival – ca. 4%

Diagnosis establishedDiagnosis established

general status (Karnofsky)general status (Karnofsky)

supportive caresupportive care TNM stagingTNM staging

palliation palliation

surgery alonesurgery alone

surgery + adjuvant therapysurgery + adjuvant therapy

chemotherapychemotherapy

Combined therapyCombined therapy

• Neo-adjuvant therapy = before surgeryNeo-adjuvant therapy = before surgery

• Adjuvant Adjuvant = after surgery = after surgery

• Sequential or concomittant (eg. CTH & RTH)Sequential or concomittant (eg. CTH & RTH)

T staging

T3 –locally advanced

Extends beyond pancreas but no involvement of celiac axis or superior mesenteric artery

Potentially resectable in expert centres

T4

Involvement of celiac axis or superior mesenteric artery

No or N1 (number of lymph nodes involved does not need to be defined

Stage groups

Stage 0 Tis N0M0

Stage I A T1 N0M0 potentially resectableStage I B T2 N0M0

Stage II A T3 N0M0 usually potentially resectableStage II B T1-3 N1M0

Stage III T4 N0-1 M0 locally advanced, not resectable due to CA or SMA involvement

Stage IV T1-4 N0-1 M1 metastatic

ResectionResection• RR classification classification ( (rresidual tumouresidual tumour))

– R0R0:: tumour resected macroscopically and tumour resected macroscopically and microscopically completely microscopically completely

– R1R1: : tumour resected completely macroscopically tumour resected completely macroscopically but incompletely microscopically but incompletely microscopically

– R2R2: : resection incomplete macroscopicallyresection incomplete macroscopically

Stage I/II patients

Neoptolemos NEJM, 2004

ESPAC-3ESPAC-3• The largest ever trial on adjuvant therapy in The largest ever trial on adjuvant therapy in

pancreatic cancerpancreatic cancer

• 1100 patients in 17 European counties1100 patients in 17 European counties

• Arm A: Arm A: 5-FU/folinic acid5-FU/folinic acid

• Arm B: Arm B: gemcitabine day 1,8,15 every 28 daysgemcitabine day 1,8,15 every 28 days

• Results areResults are awaited awaited

Clear benefit from adjuvant chemotherapy after resection

Standard adjuvant therapiesStandard adjuvant therapies

• USA – adjuvantUSA – adjuvant chemoradiotherapy chemoradiotherapy • Europe – adjuvantEurope – adjuvant chemotherapy chemotherapy

Debate continuesDebate continues

Advanced disease - usual survivalAdvanced disease - usual survival• Localized disease Localized disease – ca. 1 year– ca. 1 year

• Metastatic disease Metastatic disease – ca. 6 months – ca. 6 months

• Endpoints:Endpoints:– Overall survivalOverall survival– Quality of lifeQuality of life– Clinical benefit response (CBR): (pain, KPS, Clinical benefit response (CBR): (pain, KPS,

weight)weight)

Main agents for chemotherapyMain agents for chemotherapy

• 5-FU – 5-FU – 600 mg/m2 weekly600 mg/m2 weekly

• Gemcitabine – Gemcitabine – 1000 mg/m2 weekly for 7 1000 mg/m2 weekly for 7 weeks (1 week off) + wekly 3 weeks with 1 weeks (1 week off) + wekly 3 weeks with 1 week offweek off

5-FU vs gemcitabine5-FU vs gemcitabine

5-FU5-FU GemcitabineGemcitabineSurvival (median)Survival (median) 4,4 mo 4,4 mo 5,6 mo5,6 mo12 month survival12 month survival 2% 2% 18%18%CBRCBR 4,8% 4,8% 23,8%23,8%

FDR GemcitabineFDR Gemcitabine• Increasing time of infusion holding the dose Increasing time of infusion holding the dose

rate constantrate constant

• Conflicting resultsConflicting results

• Most administer the drug in a standard wayMost administer the drug in a standard way

Capecitabine (Xeloda)Capecitabine (Xeloda)• OrallyOrally• Pro-drug of 5-FUPro-drug of 5-FU

• Combination Combination Gemcitabine+capecitabine Gemcitabine+capecitabine vs vs gemcitabine gemcitabine for patients Karnofsky status 90-100 pointsfor patients Karnofsky status 90-100 points overall survival benefit overall survival benefit

10,4 monts vs 7,4 months 10,4 monts vs 7,4 months

Herrmann 2007

Targeted therapiesTargeted therapies• EGFR inhibitors:EGFR inhibitors:

– ErlotinibErlotinib– cetuximabcetuximab

• VEGF inhibitorsVEGF inhibitors– BevacuzimabBevacuzimab

• OthersOthers

Real life (Institute of Oncology, Real life (Institute of Oncology, Warsaw)Warsaw)

• Resectable tumour:Resectable tumour:- adjuvant chemotherapy (gemcitabine) – - adjuvant chemotherapy (gemcitabine) –

standard dosingstandard dosing- adjuvant radiochemotherapy as research - adjuvant radiochemotherapy as research

programmeprogramme• Palliative therapyPalliative therapy

• Gemcitabine (standard) until progression or toxicityGemcitabine (standard) until progression or toxicity• Gemcitabine + Xeloda (non standard approachGemcitabine + Xeloda (non standard approach

• Second lineSecond line• FAM (5-FU+ adriamycin + mitomycin)FAM (5-FU+ adriamycin + mitomycin)• Clinical trials with anti-EGFRClinical trials with anti-EGFR

SummarySummary

• Proper staging is crucial for planning therapyProper staging is crucial for planning therapy

• Selection of patients for a given therapy is difficultSelection of patients for a given therapy is difficult

• Resectable patients should have adjuvant therapyResectable patients should have adjuvant therapy

(gemcitabine) providing good general (gemcitabine) providing good general

statusstatus

• Palliative therapy (gemcitabine monotherapy)Palliative therapy (gemcitabine monotherapy)

• Numerous trials existNumerous trials exist

Question 1Question 1Tumour extending beyond pancreas, not Tumour extending beyond pancreas, not

inflitrating CA or SMA is:inflitrating CA or SMA is:

• 1) T11) T1

• 2) T22) T2

• 3) T33) T3

• 4) T44) T4

Question 2Question 2T4N1M0 is unresectable due toT4N1M0 is unresectable due to::

• 1) metastatic disease1) metastatic disease

• 2) involvement of SMA or CA2) involvement of SMA or CA

• 3) lymph node involvement3) lymph node involvement

• 4) Karnofsky status 30%4) Karnofsky status 30%

Question 3Question 3::

Capecitabine isCapecitabine is

• 1) oral gemcitabine1) oral gemcitabine

• 2) oral 5FU2) oral 5FU

• 3) oral cetuximab3) oral cetuximab

• 4) oral oxaliplatine4) oral oxaliplatine