12-YEAR FOLLOW-UP OF A RANDOMIZED TRIAL COMPARING CISPLATIN AND CYCLOPHOSPHAMIDE WITH CISPLATIN, DOXORUBICIN AND CYCLOPHOSPHAMIDE IN PATIENTS WITH ADVANCED EPITHELIAL OVARIAN-CANCER

From 1982 to 1984, 131 patients with FIGO stage Ic-IV epithelial ovari an cancer were included in a randomized clinical trial comparing cispl atin 50 mg m(-2) plus cyclophosphamide 600 mg m(-2) (PC regimen) with PC plus doxorubicin 45 mg m(-2) (PAC regimen). Chemotherapy was repeat ed every 4 weeks for six cycles. The criteria for entry, the character istics of the elegible patients, the response rates and the toxicities have been previously reported. The study was updated in August 1994 w ith a median follow-up of 10.5 years (range 10-12 years). In the whole series, the median time to progression is 13 months and the 12-year p rogression-free survival (PFS) is 18%, whereas the median time to surv ival is 21 months and the 12-year survival is 21%. By log-rank test su rvival is significantly related to residual disease after first surger y (P<0.0001), ECOG performance status (PS) (P<0.0001), FIGO stage (P=0 .0001) and histologic grade (P=0.04), but not to type of chemotherapy and age. By Cox proportional hazard model residual disease (P=0.0004), histologic grade (P=0.01) and ECOG performance status (P=0.049), but not FIGO stage, treatment arm and age, are independent prognostic vari ables for survival. The survival curves are superimposable in the two treatment arms among patients with residual disease <2 cm, whereas the re is a trend in favor of the PAC regimen among patients with larger r esidual disease. By log-rank test PFS is not significantly related to chemotherapy arm. However, it is worth noting that among patients with residual disease >2 cm 12-year PFS is 12.5% for PAC arm, while all pa tients of PC arm progressed by the sixth year. Conversely, the PFS cur ves are superimposable in the two treatment arms among patients with r esidual disease <2 cm.