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indicate an advantage above CAV treatment. Supported by the BMFT.

Canadian Multicenter Randomized Trial Com- paring Standard (SD) and Alternating (A) Combination Chemotherapy in Extensive Small Cell Lung Cancer (SCLC). Evans, W.K., Murray, N., Feld, R., Coy, P., Clarke, D., Levitt, M., Shelley, W., Pater, J. National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario.

Patients with extensive SCLC were rando- mized to receive either 6 ~ourses of i.v.

cyclophosphamide 1009 mg/m-, doxorubicin (adriamycin) 50 mg/m- and vincristine 2 mq (CAV) at 3 week interval~ or CAV alterna- ting with VP-I~ 100 mg/m- days 1-3 and cis- platin 25 mg/m days 1-3 q 3 weeks for 6 treatment cycles. Responding patients re- ceived prophylactic cranial irradiation after 3 courses of chemotherapy. No main- tenance chemotherapy was given and thora- cic irradiation was only used to pallia- te persistant or recurrent local symptoms. Two hundred and thirteen of 230 patients randomized prior to Sept. i, 1984 were eli- gible for study (i01 on SD; 112 on A). Most had a good performance status (62% ECOG 0, l) and the two groups were well balanced for known prognostic factors. Of the 187 patients evaluable for response, 57% were classified as responders after 6 courses (17% CR; 34% PR). The response rate (CR + PR) was higher on A (61% vs 39%, p<.01) and the median progression free survival was also superior (A=30 wks SD=23 wks, p=0.001). The median survival time of the whole group was 37 wks (A=40 wks, SD=34 wks, p=0.056). The frequency of thrombocytopenia and se- vere GI toxicity was slightly greater on A but the frequency of neutropenia and in- fection was less.

This preliminary analysis suggests that A is a better treatment approach for exten- sive SCLC.

Feasibility of in Vitro Growth and Chemo- sensitivity Testing (CT) of Small Cell Lung Cancer (SCLC) Cells in a Prospective Clini- cal Trial. Ihde, D., Oie, H., Russell, E., Linnoila, I., Carney, D., Minna, J., Gazdar, A. NCI- Navy Med. Oncol. Br., Natl. Cancer Inst. and Naval Hosp., Bethesda, MD 20814, U.S.A.

Staging procedures performed in SCLC patients (pts) seldom yield specimens con- taining sufficient clonogenic tumor cells to perform CT for even a single drug. We have tried to circumvent this problem by using cell culture techniques to expand the number of tumor cells before CT with a dye exclusion assay. To determine the frequency with which in vitro CT data could be generated in SCLC pts, we initia-

ted a prospective clinical trial in pts

with untreated extensive stage or recurrent tumor. Only routine staging procedures (bone

marrow, paracentesis, biopsy of peripheral no- des or subcutaneous nodules, peritoneoecopic liver biopsy) were used to obtain tumor samp- les in all but 2 cases. Tumor-containing spe- cimens could be procured from 19 (76%) of 25 consecutive untreated pts. A major surgical procedure would have been required in the re- maining 6. Sufficient cell growth to allow CT of 7 or more drugs, usually at 3 concentra- tions, occurred in specimens from 9 pts (47% of pts with positive specimens). In 9 pts with recurrent SCLC in whom positive specimens were cultured, cell amplification that permitted CT was observed in material from 5 pts (55%). Sufficient cells to generate CT data never re- sulted unless cytology of the submitted specimen or gross appearance in the culture flask sugge- sted malignant cells were present. In 2 instan- ces CT could be performed after only a few days in culture; the remaining tests were done after 3-10 weeks. There was a wide spectrum of sensitivity to individual drugs among diffe- rent pts. We conclude that prospective collec- tion of in vitro CT data is feasible with rou- tine staging procedures in a large fraction of pts with newly diagnosed extensive stage or re- current SCLC.

Anticancer Drug Sensitivity of Lung Cancer Using The Tt~nor Stem Cell Assay. Hiraki, S., Ohnoshi, T., Kishimoto, N., Numata, T°, Kimura, I. Second Department of Medicine, Okayama University Medical School, Okayama, Japan.

It would be helpful for successful chemo- therapy of cancer patients to know accurate in vitro anticancer drug sensitivity. The pur- pose of the present study was evaluate the tumor stem cell assay reported by Salmon et al for the selection of effective drugs for indi- vidual patients with lung cancer and for the in vitro phase II screening of new anticancer drugs.

Specimens were obtained by aspiration of pleural effusions and bone marrows and biopsy of the primary and metastatic tumors. Tumor cells were exposed to drugs for one hour prior to plating. Each drug was tested at two or three dose levels which were achievable clinically. Drugs tested in the present study were adria- mycin, aclarubicin, THP-adriamycin, mitoxan- trone, 40497S (active form of ifosfamide), mito- mycin C and methotrexate.

Seventy~eight specimens were obtained from patients with lung cancer and tested drug sen- sitivity by the assay. Of 78 specimens, 57 (73%) formed at least five colonies per plate. In the analysis of colony growth rates according to histological types, small cell carcinoma was 85%, squamous cell carcinoma 78%, adenocarci- noma 68% and large cell carcinoma 67%. Of these 57 specimens, 39 formed more than 30 colonies

in control plates and were able to test drug