IN VITRO DRUG TESTING FOR LIMITED SCLC AND PHASE I DRUG DEVELOPMENT

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A protocol combining twice a day radiotherapy plus VP 16 and cisplatin for limited stage small cell lung cancer continues. Thirty-eight patients have been entered onto study and 28 of 36 (78%) patients who have completed therapy have achieved a complete remission. The projected median survival is 30 months with a median potential follow-up of 27 months. One patient has died from combined modality pneumonitis. A phase I trial using dihydrolenperone, an agent identified as being active against human lung cancer by the dosage levels. The principle side effects have been somnolence and hypotension in all patients. Six patients have had to stop therapy because of somnolence and none because of hypotension. There have been no objective responses to date. In vitro testing with dihydrolenperone showed 50% inhibition of growth of non-small cell and small cell lung cancer lines at 25-165 ug/ml. Pharmacokinetic determinations show peak absorption at 3-5 hours and plasma levels were more than 100 fold less than the levels where in vitro activity against lung cancer cell lines was observed. From this studies we conclude that the HTCFA has identified a compound with novel side effects, the maximum tolerated dose is 50 mg per square meter, and achievable plasma levels are much less than that required for in vitro activity.