Summary Ten human ovarian carcinoma cell lines have been studied as a potential in vitro screen for the development of novel anticancer platinum complexes. Lines have been established and developed both from solid and ascitic tumours, from pretreated and untreated patients, and are available at a range of in vitro passage numbers. The biological properties of the lines were consistent with them being human, epithelial and of ovarian carcinoma origin. Using a tritiated thymidine or leucine uptake method, and a 96 hour continuous drug exposure, the lines have been calibrated against four platinum-containing chemotherapeutic agents: cisplatin, iproplatin, carboplatin and tetraplatin. Striking differences in cytotoxicity were observed across the lines for each agent. Some lines were consistently resistant, others generally sensitive, whereas some showed clear evidence of differential sensitivity to a particular agent. Statistical analysis (Spearman rank correlation) involving the six possible pairings of drugs showed that cisplatin, iproplatin and carboplatin elicit a very similar pattern of response in these lines whereas tetraplatin elicits a completely different response pattern. Similar cytotoxicity values were obtained using a soft agar cloning assay. Results using a tetrazolium dye reduction assay, however, gave somewhat higher and more variable values, particularly with tetraplatin. The thymidine uptake assay will be adopted in further studies on a selected panel of six lines. This panel encompasses the spectra of sensitivities identified for each of the four agents against the original ten lines and may provide a useful screening facility for the development of novel platinum drugs, in that it detects both cell line-determined and structure-determined differences in cytotoxicity.Traditionally, the development of new drugs for the treatment of malignant diseases has relied predominantly on transplantable murine tumour models, such as those used by the National Cancer Institute (NCI) (Frei, 1982;Venditti, 1983). Such models include the P388 leukaemia, L1210 leukaemia, Lewis lung carcinoma, B16 melanoma, Colon 38 and CD8F1 mammary carcinoma. Our earlier work, which predicted the clinical antitumour activities of the platinum analogues JM8 (carboplatin) and JM9 (iproplatin), exploited predominantly the platinum-sensitive ADJ/PC6 murine plasmacytoma (Harrap et al., 1980;Harrap, 1985). Other workers have generated cisplatin-resistant variants of the L1210 and P388 tumours in attempts to identify novel platinum drugs which might exhibit wider spectra of antitumour activities (Burchenal et al., 1979(Burchenal et al., , 1980. Tetraplatin exhibits no cross-resistance in such models and is currently under preclinical development at NCI (Anderson et al., 1986). A recent reappraisal of screening models at the NCI has resulted in the replacement of the in vivo murine panel in favour of a range of in vitro human tumour cell lines representative of the major histological types (Boyd, 1986).Clinical trials using platinum-con...

Eighteen patients with small cell carcinoma of the lung received high dose cyclophosphamide (180-200 mg/kg) intensification following five pulses of 'CHOP' chemotherapy (cyclophosphamide 750 mg/m2 i.v., adriamycin 50 mg/m2 i.v., vincristine 1.4 mg/m2 i.v., prednisolone 40 mg orally for 5 d). They received infusions of autologous bone marrow which had been stored at 4 degrees C for 34 h. Pancytopenia was predictable in onset and its duration acceptable. Recovery of neutrophils to greater than 1.0 x 10(9)/l was achieved in 17.5 +/-0.9 d (mean +/- SEM) and platelets to greater than 100 x 10(9)/l in 17.5 +/- 0.8 d. Four patients with acute myeloid leukaemia in complete remission received intensification with the supralethal combination of cyclophosphamide and total body irradiation followed by infusion of autologous marrow which had been stored at 4 degrees C for 54 h. Haematological reconstitution in these patients was acceptable but slower (greater than 1.0 x 10(9)/l neutrophils between days 26 and 40; greater than 20 x 10(9)/l platelets between days 23 and 77). Except in one case, normal peripheral counts were attained in all patients. It is concluded that bone marrow stored at 4 degrees C for up to 54 h is a simple and practical source of viable stem cells which have the capacity for acceptable haematological reconstitution.

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