Prognostic factors in advanced epithelial ovarian cancer. (Gruppo Interregionale Cooperativo di Oncologia Ginecologica (GICOG)).

The data on 914 patients enrolled in four randomised trials in advanced ovarian cancer, consecutively conducted by the same cooperative group between 1978 and 1986, were analysed with the aims of: (1) determining the impact of selected prognostic variables on survival; (2) finding, from the interaction of favourable prognostic factors and treatment, an approximate estimate of the magnitude of the survival advantage associated with the use of platinum-based combination chemotherapy. The overall 3-year survival in this series of patients is twice that reported historically (22%; 95% CL 18.7-25.4). The proportional hazard regression model was used to perform the analysis on survival. Residual tumour size, age, FIGO stage and cell type were all independent determinants of survival. Differences in survival from the various prognostic groups were impressive with 5-year survival rates ranging from 7 to 62%. However, these differences were not qualitative (i.e. the kinetics of survival were similar for the best and the worst groups) suggesting that current prognostic factors are of little use for selecting 'biologically' different sub-populations. Platinum-based regimens were associated to an overall prolonged median survival, but this benefit was not observable in the subgroup with most favourable prognosis (less than 2 cm residual tumour size). The implications of these observations for clinical research and ovarian cancer patients care are discussed.

Randomized trial in advanced ovarian cancer comparing cisplatin and carboplatin.

The aim of this multicenter randomized trial was to compare carboplatin (400 mg/m2) and cisplatin (100 mg/m2) in patients with untreated advanced epithelial ovarian cancer. Toxicity and treatment efficacy assessed by pathological response rate, progression-free survival, and survival were the endpoints of the study. One hundred seventy-three patients with advanced epithelial ovarian cancer, F.I.G.O. (International Federation of Gynecology and Obstetrics) stage III and IV were accrued in the trial. The median follow-up time was 15 months (maximum, 34); three patients in each treatment arm were not eligible (four, nonepithelial ovarian cancer type; one, no data, and one, stage II). Patient characteristics were similar in the two groups. In the carboplatin-treatment arm, the overall pathological response rate was 57.3% and the complete pathological response rate was 26.8%. In the cisplatin-treatment arm, the overall pathological response rate was 71.6% and the complete pathological response rate was 24.7%. There was no statistical difference in the two arms in survival or progression-free survival. Cisplatin was more nephrotoxic while carboplatin induced a higher degree of myelosuppression, especially thrombocytopenia; however, severe hematological toxicity was seldom observed. Carboplatin is a cisplatin analog with definite activity in ovarian cancer, but it is more active than the parent compound. Because of less nonhematological toxicity, carboplatin is undoubtedly a useful substitute in patients who cannot be given cisplatin. Further experience is needed to indicate whether or not carboplatin should completely displace cisplatin in the clinical treatment of ovarian cancer.

Methotrexate with citrovorum factor in low-risk gestational trophoblastic tumor.

From January 1976 through December 1985, methotrexate (MTX) with citrovorum factor (CF) was administered as primary treatment to 57 patients with low-risk gestational trophoblastic tumor (GTT); 51 patients were non-metastatic and 6 were metastatic GTT. The median number of courses needed to achieve biochemical remission was two (range, 1-7). Complete remission was attained in 95% of non-metastatic GTT patients with postmolar persistent trophoblastic disease, but when choriocarcinoma was histologically confirmed, this fell to 60%. The cure rate of metastatic GTT patients was only 50%. The overall remission rate with the MTX-CF combination was 84.2%. Toxicity was mild, consisting of myelosuppression and mucositis. Fifteen patients were resistant to MTX-CF, or relapsed subsequently, but they all achieved remission with chemotherapy rescue treatment (VP 16 alone, EMA/CO, CHAMOCA). Two patients required a pulmonary lobectomy. They are all still alive in biochemical remission with a median survival of 54 months. Our experience suggests that drug resistance and relapse rate seem related to a beta-HCG value higher than 10(4), an enlarged uterus with myometrial deep involvement, and a histologically confirmed diagnosis of choriocarcinoma. In conclusion, the MTX-CF combination is effective in postmolar GTT, whereas a different therapeutic approach may be considered for a "special" low-risk group of patients, on the basis of prognostic factors.

Evaluation of the interaction of mononuclear phagocytes with ovarian carcinoma cells in a colony assay.

The effect of human peripheral blood monocytes on the SW626 ovarian carcinoma line was investigated in a colony assay in agar, Percoll-enriched monocytes inhibited colony formation by SW626 carcinoma cells at effector-to-target cell (E:T) ratios as low as 0.3:1. In contrast the same effectors had little cytolytic effect in a 48 h thymidine-release assay at E:T ratios as high as 40:1. Monocyte-depleted nonadherent cells had little inhibitory capacity on SW626 colony formation, whereas unseparated mononuclear cells were intermediate between Percoll-enriched monocytes and lymphoid cells. Sorting of cells positive for the monoclonal antibody marker MO2 confirmed the monocytic nature of cells which inhibited colony formation. Ovarian carcinoma cells freshly isolated from 9 patients were heterogenous in their susceptibility to colony inhibition by mononuclear phagocytes. Cells from 4 patients were not inhibited by effector cells and in one subject promotion of colony formation by mononuclear phagocytes was observed. With 4 cell preparations inhibition of colony formation was found as with the SW626 line. Colony assays may provide a useful methodological approach, particularly when effector cells mediate low levels of killing, of doubtful biological significance, in conventional isotope release assays, or when growth promotion is to be evaluated.