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compared to those of 110 gastric adenccarcinoma tissues, using the in vitro succinate dehydrogenase inhibition (SDI) test. Tumour tissues obtained at surgery were exposed to five different anticancer drugs: carboquone (CQ), adriamycin (ADM), mitomycin C (MMC), cisplatin (DDP) and 5-fluorouracil(5FU). The lung adenocarcinomas showed a statistically significant reduction in succinate dehydrogenase (SD) activity. compared to the gastric adenocarcinomas, after exposure to each drug. The chemoscnsitivity was defined as a reduction in SD activity to 50% of control or less. Lesser degrees of reduction in SD activity were defined as drug resistance. The sensitivity rates to ADM, MMC and DDP, respectively, were signiticantly higher in the lung than in the gastric adenocarcinomas. Tumour cells from 22 (84.6%) of the 26 lung adenocarcinoma tissues showed a sensitivity to more than three drugs, whereas the rate was only 46.4% (51/110) for the gastric adenocarcinomas.Therateofrcsistance toall thedrugstested was 3.8% (l/26) for the lung adenocarcinomas, in contrast to the 20.9% (23/l 10) seen with the gastric adenocarcinomas. Thus, while adenccarcinomas of the lung and stomach both show clinical resistance to anticancer agents, thechemosensitivity of the lung tissues is greater. In the light of these observations, attention must be directed to improving specific drug delivery systems.

Phase I study with combination therapy of pirarubicin, etoposide, and vincristine in small-cell lung cancer Patzer DC, Koschel G, Greifenbcrg B, Kaukel E. Deporfmenf of Pneumology. Horburg General Hospital, 2100 Hamburg 90. Am J Clin Gncol Cancer Clin Trials 1990;13:Suppl l:S24-8.

The toxicity and efficacy of the combination of pirarubicin (THP), etoposide, and vincristine were investigated in a phase I trial. The dose of THP was modified in steps of 10 mg/m” or 5 mplml differences, starting with40mg/m2i.v. onday 1. Dosesofetoposide(100mg/m2i.v. days l-3) and vincristin 2 mg i.v. day 1) remained constant. The schedulewasrepeatedevery 3 weeks. A minimum of four patients were recruited at each dose level. The maximum tolerated dose (MTD) was defined as follows: toxicity WHO grade 3 and 4 in five of eight patients of one dose step (exception: leukocytopenia at the time of nadir WHO grade 4 is relevant for the MTD). Currently, 20 patients have been treated. The administered dose levels of THP were (mg/m’): 40 (5 patients), 50 (4 patients), 55 (6 patients), and 60 (5 patients). Screening of cardiac function (ECG, ultrasound cardiography) was performed at the start of the treatment and before each course. There were no signs of cardiotoxicity up to a cumulative dose of 360 mg/m*. Leukocy- topenia WHO grade 3 was observed in seven courses (12%), and grade 4 was observed in two courses (3%) as main side effects. The subjective tolerability (nausea, vomiting, and alopecia) was mild to moderate. We decided upon 55 mp/m* MTD because WHO grade 4 leukocytopenia developed in one patient after the first course and two not conclusively clarified early deaths occurred at the 60 mp/m” pirarubicin dose level. Eighteen patients were evaluable for response: one CR (6%). eight PR (44%). four NC (22%). one EP (6%). and four ED (22%). This means a response rate of 50% and a median survival time of 10 months. We have initiated a phase II study with the elaborated schedule.

Pirarubicin phase II study in untreated metastatic small-cell lung careinoma:AcooperativestudyoftheGroupeFrancaisdePneumo- Cancerologie (GFPC) Kleisbauer JP, Vergeret J, Balmes P, Arnaud A, Taytard A, Targhetta R et al. Hopital Sainte Marguerite, 270, Bd Ste Marguerite, F-13009 Marseille. Am J ClinOncol Cancer ClinTrials 1990;13:Suppl l:S20-3.

Piiarubicin (THP) (Roger Bellon Laboratory, France) is a new anthiacycline under clinical development. In order to assess the effi- cacy and toxicity of the drug in small-cell lung carcinoma (SCLC), we have undertaken this trial in front-line therapy in patients with metas- tatic disease, PS < 3 and at least one evaluable lesion. Responses were assessed after two cycles of THP (60 mp/ml i.v. bolus every 3-4 weeks) and a further cross over to VP16 + CDDP (three cycles) was systematic whatever the response to THP. This crossover was performed after only onecycleincase ofobviousprogression. From June 1988 to April 1990, 32 patients were enrolled: 6 were ineligible (4 non-SCLC, 2 M& 26 patients were fully evaluable for THP and 18 patients for VP1 6CDDP.

The characteristics of the patients were as follows: mean age 57.4 years (38-71): T,: 54%; T,: 27%; T,: 19%; N,: 62%; N,: 35%; N,: 4%. The efficacy was as follows: 1 complete response and 2 partial responses (confiimed by endoscopy); 12 patients received only one cycle because of obvious progression; the overall response rate is 12% (95% conti- dence interval 024%). The patient who had complete response after pirarubicin remained in CR after VPl6-CDDP, whereas the 2 patients who had partial response achieved CR for one and PR for the other; among the 15 who did not respond 1 CR and 7 PR were observed. The only significant toxicity of THP was granulopenia without infection. THP seems to be an effective anthracycline in SCLC, and the study is continuing. A response could be reached in 50% of the nonresponders with standard therapy and 10 of 24 patients (42%) finally responded. Therefore, this schedule for testing new drugs in metastatic SCLC appears ethically acceptable.

Cyclic-alternating versus response-oriented chemotherapy in small- cell lung cancer: A German multicenter randomized trial of 321 patients Wolf M. Pritsch M, Drings P, Hans K, Schroeder M, Flechtner H et al. Division of HemarologyiOncology, Deportment of Internal Medicine, Philipps-University Hospitals, Baldingerstrasse, D-3550 Marburg. J Clin Gncol 1991;9:614-24.

To test whether alternating chemotherapy is a favorable treatment modality in small-cell lung cancer (SCLC), 334 patients were random- ized to receive either fixed cyclic-alternating treatment with ifosfa- middetoposide (IE), cyclophosphamide, doxorubicin, and vincristine (CAV), or response-oriented treatment with IE therapy up to maximal response and subsequenlly an immediate switch to CAV. In both arms, six cycles were given in 3-week intervals. After chemotherapy, patients with limited-stage disease received chest irradiation with 45 Gy. Prophylactic cranial irradiation with 30 Gy was applied to all complete responders. No maintenance therapy was given to patients with com- plete response. Minimum follow-up was 2 years. Of 321 assessable patients, the overall response rate was 70% for cyclic alternating and 77% for response-oriented treatment. Complete remission (CR) rates were 26% versus 26%. The median survival times were 9.7 months for cyclic-alternating versus 10.7 months for response-oriented treatment: the 2-year survival rates were 11% versus 9%. In limited-stage disease (LD) patients, there was a median survival of 12.5 months versus 12.3 monthsanda2-yearsurvivalmteof2l%versus18%.Inextensive-stage disease (ED) patients, median survival was 8.5 versus 9.1 months, and the 2-year survival rate 3% versus 4%. Fmm these results, we conclude that the cyclic-alternating treatment according to the hypothesis of Goldie et al has no advantage in comparison to a sequential treatment strategy with an immediate switch to a second-line protocol at the time no further response to first-line therapy is seen. Our major aim in the treatmentof SCLC is to administer an activeregimen at any timeduring the course of treatment regardless of whether sequential or alternating therapy is used.

A randomized trial in inoperable non-small-cell lung cancer: Vin- desine and cisplatin versus mitomycin, vindesine, and cisplatin versus etoposide and cisplatin alternating with vindesine and mito- mycin Fukuoka M, Masuda N. Furuse K, Negoro S, Takada M, Matsui K et al. Department oflnternal Medicine, Osaka Prefectural Habikino Hospi- lal,3-7-1 HabiKno. Habikino. Osaka583. JClin Oncoll991;9:606-13.

Patients with inoperable non-small-cell lung cancer (NSCLC) were randomly assigned to receive one of three dosage regimens: (1) vindes- ineand cisplatin (VP); (2) mitomycin, vindesine, and cisplatin (MVP): or (3) etoposide and cisplatin alternating with vindesine and mitomycin (EP/VM). In 199 assessable patients, the response rates were VP, 33%; MVP, 43%; and EP/VM, 19%. The addition of mitomycin to the VP regimen did not significantly improve the response rate. The response rate was significantly lower wirh the EP/VM regimen than with the MVP regimen (P < .Ol). The median survival times were VP, 50 weeks; MVP, 42 weeks; and EP/VM, 40 weeks. These differences were not significant. Grade Ill or IV thrombocytopenia was significantly greater (P -z .Ol) in MVP patients (22%) than in the VP (5%). Other toxicities