199

623+633.

Chcsr wall invasion by bronchogcnlc carcinoma is found in 5% ofall casts of pulmonary carcmoma. During the last 3 years, I1 cases of lung cancer with chest wall mvolvemcnt have been encountered at the Jackson Vctcrans AdministratIon Medical Center. We reviewed these cases to reassess the role of concorm(ant resection of the lung and chest wall. From this expenence, WC have concluded that (I) chest wall mvolvemcnt IS potentially curable; (2) chest wall resection adds little if any morhtdity to the procedure; (3) resections of fewer than four ribs usually require only soft tissue coverage, without a prosthesis; (4) patients wch squamous ccl] cancer have longer surwval; (5) chest wall resection 1s tughly effective in the rclicf of pam due to mvasion of the chest wall; and (6) survwal IS greater than in ocher stage III lung carcinomas and 1s more closely rclaccd to nodal involvement than to chest wall mvaston.

Surgical treatment of small cell lung cancer Wada H, Hltomi S, Yutaka TG, Shido TT, Aoki M. Departmen of Thoracic Surgery, Chesl Disease Research Insiwe, Kyoro Unwersi:y,

Kyom. Jpn J Thorac Dis 1990;28: 197-202. Thirty four small cell lung cancer (SCLC) patients underwent opera-

tion in Kyoto Umversity from 1976. The mean age was 62 years old; 25 male cases, 9 female, respectwcly. All case were limited disease 0-D) cxccpt 2 parwts with rib metastasis. Seventeen pauents had a perforn- ancc status (PS) of0 and l7PS 1. twenty eight patients were treated with chemotherapy. Of the remaining 5 palien& 2 were treated by only oral S-FU denvatws, one died within 30 days of operation, one could not be treated owing IO old-age, and one refused chemotherapy. Except one operational death 33 cases were able to be evaluated. Out of 28 patients I6 patienti were treated by only postoperativechemotherapy. Concern- mg operatIonal radlcahty, 21 casts out of 31 were operated radically (68%). The survival rates of these 33 patients were 78% 37% at I ,3 and 5 years respectively. The MST was 26 months. The neoadjuvant group head better results than the nonadjuvant group.

Present status and problems of surgical treatment of non-small cell lung cancer Fujisawa T, Yamaguchl Y, Shiba M et al. Deparlmenr of Sw~ery,

Innsrlrure of Pulmonary Cancer Research. Chiba University School of Medicine, Chiba 280. Jpn J Thorac DIS 1990;28:210-5.

Surgical treatment and combmcd chemotherapy of non-small cell lung cancers durmg the last IO years were analyzed. Overall 5 year survwal race of non-small cell lung cancer was 37% and those in stages I,Il,IlIA and IIIB were 59%. 33%. 21% and 12%. respectively. Poor outcome in IIIA cases depended strongly on surgical rewxablity, however, adcnocarcinoma cases depended more on the T factor and squamous ccl1 carcinoma depended more on the N factor. IIIA cases, cvcn though resected curatively, shows 10.20% local recurrence, mdlcatmg the importance of further improvement of the surgical procedure. In the cases with absolutely noncurative resection tumor remained in medlastmal lymph nodes or organs adjacent to the medi- astmum, indicating the necessity ol extended combined resection including contralateral mediascial lymph nodes or organs adjacent to the medlascinum for better results of surgical treatment. Preoperative chemotherapy for the supression of local recurrence and distant metas- tasis was significant only in very limited circumstances.

Limited operation for lung carcinoma to preserve lung function Shiba M, Yamaguchi Y, Fujisawa T et al. Deparlmen~ of Surgery,

lnslilule of Pulmonary Cancer Research, Chiba University, School of Medicine, Chibashi. Jpn J Thorac DG 1990;28:260-4.

A clinical study on 207 patients was performed to evaluate partial or wedge resection for lung carcinoma in our insciture. Although forced wtal capacity decreased 300 ml in cases with poor lung function, blood gas analysis and performance status showed no change due to limited operauon. Relative noncurative cases undergoing limited operation showed a relatively good result compared to standard lobectomy, and the S-year survival rate was 42% postoperatively, but absolute noncu- ratwe cases showed amuch poorerpostoperativeprognosis. Reduction surgery by limwd operation did not have significant effect on the

survival of the patients. Limited operauon for recurrent lung cancer showed good results and S-year survival was 60% postoperatively. It W&F suggcsced that limited operation for such selected pacicnl? can bc a beneficial therapcuuc modality. In conclusion, hmited resection IS not Indicated for peripheral lung cancers of more than 3 cm m dmmcter, poor drffercntiaclon or marked cell atypla, because of higher rncidence of lymph node melastasls and early postoperative recurrence, especially m adenocarcinoma.

Results of pulmonary angioplastic operations for cases of broncho- genie carcinoma Ayabe H, Kawahara K, Tagawa Y et al. The Frrsr Deparrmenr of Surgery. Nagasaki University School of Medicme. Nagasaki. Jpn J Thorac Dis 1990;28:278-83.

Pulmonary artcry rcconstruc~~on for bronchogcruc carcinoma was performed in 36 pacicne (5.8%) in our department between 1955 and 1988 for thepurposeofprcscrvation ofpulmonary funct~on.Twenty-six patients had squamous cell carcmoma (72.2%) and 24 had Stage IllA. The operative procedures were sleeve resection of the main pulmonary artery (P.A.) and end-co-end anastomosis m 20 cases, wedge resection of P.A. and transverse suture m I4 and wmdow type resection of P.A. and patch closure in 2. In 28 patients bronchoplastic procedures were combined. Three pauents (X.3%) died wttun 30 days after operation. Postoperative complications were relatively lxgh in the patznts wth combmed aperatIons. The 5.year survival rates wcre45.7%. Postopera- tive pulmonary functions were evaluated wch spirometic exammations and pulmonary scintigrams. There were no differences in postoperatwe pulmonary functions between pulmonary angioplastic procedures and simple lobectonucs. In conclusion, with a shghtly high tendency of postoperative complications, pulmonary artery reconstruction for the patlcnis with lung cancer is an acceptable operauon to obtain curability as cancer surgery and preserve pulmonary function at a level compa- rable co slmplc lobectomy.

Long-term survival after chest-wall reconstruction with mosculo- cutaneous flaps Kroll SS, Schusterman MA, Larson DL, Fender A. Seclron of Plaslic

Surgery, Box 69, M.D. Anderson Cancer Cemer, ISIS tloicombe

Boulevard, Houston, 7X 77030. Plasc Reconsu Surg 1990;86:697-701. Reconstructron of chest-wall defects with musculocutaneous flaps

pernuts resection of advanced chest-wall tumors and of tissues severely damaged by radIotherapy in patients who in a previous era were not surgically treatable. To determine the long-term outcome from this surgery, the records of 96 patients who had undergone chest-wall resection with musculocutaneous flap reconstruction were reviewed. Median survival for the enwe group was 20.5 months, but a more accurate prcdictlon of outcome could be obtained by dividing the patients into three groups. In group I, patznts free of known malignancy and undergorng rcscction of radionecrotic twues, median survival was 60.0 months. In group II, patients with resectable disease and free of tumor following surgery, median survival was 31.1 months. In group III, pa~lenu incompletely resected or known to have metastatic &ease following surgery. median survival was only 12.5 months. Even m group III, however, some indiwduals aclneved prolonged survival and lasting benefits from the surgery, so these data should not be used to exclude paucnts from undergoing nccessaq paillative procedures.

Chemotherapy

A phase II trial of high-dose cytarabine and cisplatin in previously untreated non-small cell carcinoma ofthe lung. A Piedmont Oncol- ogy Association Study White DR, Powell BL, Craig JB et al. Cancer Cenrer, Wake Fores1

University, Bowman Gray School of Medicine, Winston-Salem. NC.

Cancer 1990;65: 1700-3.

Thirty-seven chemotherapy-naive patients with advanced non-small cell lung cancer (NSCLC) were treated with cytarabine (3 g/m2 intrave- nously [IV] during3 hours)afterIV boluscispIatin(100mg/m2repeated

200

every 3 weeks). Aside from nausea and vomiting, the principal toxicity was hematologic, with Grade IV myelosuppression in 32% and Grade III in 14%. Four patients died while on study. One complete and four partial responses were observed for an overall response rate of 14%. Responses were limited to lymph node and lung metastases and oc- curred in two of 17 adenocxcinomas, two of 12 squamous cell carcmo- mas, and one of eight large cell carcinomas. At this dose, the plasma level of cisplatin is only 3 pg/ml and the plasma level of cytarabine is IO to 50 !&ml, compared with the levels of 10 pg/ml and 1000 &ml, respectively, required for in vitro synergy. The severity of myelotoxic- ity observed indicates that, even at these levels, cisplatin enhances cytarabine actiwty. The combination may prove useful in malignancies that are sensitive to cytarabine, but is not of benefit in cytarabine- resistant malignancies such as NSCLC.

A randomised trial ofcisplatin and vindesine versus supportive care only in advance non-small cell lung cancer Woods RL, Williams CJ, Levi J et al. Department ofClinical Oncology, Royal Norrh Shore Hospiml. Sydney, NSW 2065. Br J Cancer 1990;61:608- 11.

The value of chemotherapy in advanced non-small cell lung cancer (NSCLC) remains contenttous. Because of this two separate but very similar trials were set up in Australia and Southampton (UK). Two hundred and one patients with stage IIlb or IV NSCLC were randomly assigned to cisplatin 120 mg m 2 on days I and 29 and vindestine 3 mg m 2 weekly x 6 or to no chemotherapy. Both groups were eligible to receive radiotherapy or other palliative treatment as required. Of 188 evaluable patients, 97 received chemotherapy and 91 were in the control arm. Response was assessed between days 42 and 49. Respond- ers continued chemotherapy at the same doses through cisplatin being given 6 weekly x 4 and the vindesme 2 weekly x 12. The overall response rate to chemotherapy was 28%; there were no significant differences according to major prognostic criteria. Although the overall survival of the chemotherapy group (median 27 weeks) was longer than that of the no chemotherapy group (mcdmn 17 weeks) this was not statistically significant (log rank P = 0.33). For patients without dis- scmmation (IIlb), median survwal was 45 weeks m the chemotherapy arm and 26 weeks in the non-chemotherapy (log rank P = 0.075). Toxicity was universal and frequently severe: of 17 patients discontinu- ing chemotherapy after one cycle, 13 did so because of unacceptable toxicity. This chemotherapy cannot be recommended as routine treat- ment. Further phase III studies of chemotherapy m advanced NSCLC should continue to use a no chemotherapy control and should also attempt to measure quality of life, an issue not addressed effectively in this or other recent trials.

Addition of verapamil and tamoxifen to the initial chemotherapy of small cell lung cancer: A phase I/II study Figuercdo A, Arnold A, Goodyear M et al. llamillon Regional Cancer Cenlre. 711 Concession &eel, Hamilton, Ont. LAV lC3. Cancer 1990;65:1895-902.

Based on experimental observations that vcrapamd and tamoxifen reverse multipledrugresistance, theauthors investigated the feasibility of combinmg both agents with the initial chemotherapy of extensive small cell lung cancer. Overall, in a consecutive series of 58 patients the most important toxicity was myclosuppression, and there was a 24% rate of severe infections. Thcrapcutic results mcluded 24% complete and 34% partial response rates, median (Ime to disease progression of 32 weeks, and median survival of 46 weeks. In three conseculive cohorts of patients the dose of either tamoxifen or verapamil were escalated by 25% and 33%, respectively. The cohort of patients receiv- ing verapamil 360 mg/day and tamoxifen 100 mg/day (level 2) had slightly more toxicity but also more responses than the other groups. Therefore, the authors recommend that these doses be used in controlled trials IO confirm the promising results of their study.

Carboplatin, etoposide, and ifosfamide as intensive chemotherapy for small-cell lung cancer Smith IE, Perren TJ, Ashley SA et al. Lung Unit, Royal Marsden ffospiml. Downs Road, Sutton. J Clin Oncol 1990;8:899-905.

Thirty-two previously untreated, fit patients with small-cell lung

carcinoma (SCLC) were treated with an intenwe combination chemo- therapy regimen, with the aim of prolonging survival, as follows: carboplatin 400 mg/m2 intravenously (IV) day 1, ifosfamide 5 g/m’ IV day 1 in a 24-hour infusion with mesna, and etoposide 100 mg/m* IV days 1 to 3, repeating at 28-day intervals for six courses. Limited- disease (LD) patients were given concurrent hypcrfractionated radio- therapy for the first two courses, and all patients achieving a complete remission (CR) were offered prophylactic cranial irradiation (PCI). For 18 LD patients, the overall response was 94% with 72% CRs. For 14 extensive-disease (ED) patients the overall response was 100% wth 29% CRs. Median response duration for LD patients was 11.5 months and for ED patients 7.5 months. Median survival for LD patients was 19 months with a predicted 24% Z-year survival and for ED patients 9.5 months with aprcdicted 14% 2.year survival. Hematologic toxicity was severe with 100% developing World HealthOrganization (WHO) grade 3-4 neutropenia and 94% WHO grade 3-4 thrombocytopenia during treatment. Seventy-two percent of patients required a dose reduction at some stage during treatment because of ncutropenic infection or throm- bocytopcnia requiring platelet transfusions. Despite very high response rates, this intensive regimen achieves survival results only modestly better, if at all, than thosereported for less toxic conventional regimens.

Phase II study of carboplatin in patients with nonresected lung cancer KimuraK,SuzukiA,Konno Ketal.DeparrmeniofC~inicalPathology, Nippon Medical School, l-f-5 Sendagi, Bunkyo-ku, Tokyo 113. Cancer Chemother Pharmacol 1990;26:101-4.

A multicenter phase II trial of carboplatin, a new platinum analog of cisplatin, was carried out in bronchogenic carcinomaat 17 institutions throughout Japan. Of 139 patients enrolled in this trial, 10 were excluded from analysis as inevaluable and the remaining 129 were judged Lobe evaluable for response and toxic effects by the Extramural RcviewCommittee.Patientsweretreatcd i.v. witbeither300or400mg/ m2 carboplatin every 4 weeks. Responses and toxic effects were assessed at both dose levels. The overall response rate was 17.8% (23/ 129), with response rates of28.4% (19/67) for small-cell disease, 7.1% (2/28) for squamous-cell carcinoma, and 6.9% (z/29) for adenccar- cinema. The most frequent toxic cfCects were thrombocytopenia and leukopcnia, with a platelet count of <7 x 104 pl recorded in 60 patients (46.5%) and a WBC comtt of<3,OOO/pl recorded in 60 cases (46.5%). Vomiting occurred in 28 patients (21.7%). Renal, aural, and neurotox- lcltics were not seen. Hydrauon was not required. Carboplatin was demonsuatcd to bc actlvc against lung cancer, especially against small- cell lung cancer.

Phase II study of 4’-epi-dororubicin in patients with untreated, extensive small cell lung cancer Eckhardt S, Kolaric K, Vukas D et al. NaGonol fnsfilute ofOncology, Budapest. Med 0x01 Tumor Pharmacother 1990:7: 19-23.

The purpose of the study was to Investigate the antitumour activity and toxicity of high dose (120 mg m l) single agent cpirubicin therapy in untreated extensive small cell lung cancer patients. Out oC80 patienrs entered, 71 were evaluablc for both antitumour activity and toxicity, 4 only for toxicity and 5 were lost for follow-up. The drug possessed a high antitumour activity, the overall response rate was 47.9% (34nl) with 4 complete remissions (CR) and 30 partial remissions (PR). The median remission duration was 3.5 months. Particular drug activity was observed in the primary tumours, lymph nodes and pleural metastaws. Toxicity (leukopema, anaemia, vomiting, reversible rhythmic cardiac disorder, stomatitis) was mild, alopecia was reglstcred less than in adriamycin medicauon. One fatal congestive heart failure occurred. The actual mean survival time calculated on the basis of the data gained from 64 patients was 7.0 months (range 2-22). The high antitumour activity andno increase in toxicity justify the incorporatlon of high dose epirubicin into combination therapy.

Combinationcyclophosphamideandetoposideintreatmentofsmall cell lung cancer Leung WT. Shiu WCT, Pang JCK. Deparrmenl of Clinical Oncology, Prince of Wales flospital, Chmese Universiry ojffong Kong, Hong Kong. Med Oncol Tumor Pharmacothcr 1990;7:31-4.