Cisplatin-MECY (methotrexate-leucovorin rescue plus cyclophosphamide) versus cisplatin-CHAD (cyclophosphamide, hexamethylmelamine, doxorubicin, and cisplatin) as initial chemotherapy in stage III-IV ovarian adenocarcinoma.

Thirty-three patients with advanced-stage ovarian adenocarcinomas, with no prior chemotherapy, were treated with weekly cisplatin (DDP) for four courses followed by five monthly courses of one of two randomly assigned multidrug combinations. These combinations were high-dose methotrexate-leucovorin plus cyclophosphamide (MECY) or cyclophosphamide, hexamethylmelamine, doxorubicin, and DDP (CHAD). Patients with no clinically measurable disease after 6 months of therapy were evaluated by laparoscopy. In the absence of disease progression at the time of the laparoscopy the study design called for a repeat cycle of four weekly DDP courses and another five monthly courses of the assigned multidrug combination. All patients with no evidence of disease after 1 year of treatment had a second-look laparoscopy which, if negative, was followed by a second-look laparotomy. This report includes all of the consecutively entered patients observed for a minimum of 1 year or to death. DDP-MECY and DDP-CHAD were similarly active for overall response rates and complete response rates according to laparoscopic criteria. However, DDP-MECY had a statistically significantly lower relapse rate (P less than 0.02) and a statistically significantly higher negative second-look laparotomy rate than did DDP-CHAD. Using all entered patients, with no exclusions from analysis, eight of 17 patients (47%) treated with DDP-MECY had negative second-looks after 1 year of treatment. This compares with one of 16 (6%) negative second-looks in patients treated with DDP-CHAD (P less than 0.02). The high negative second-look rate with DDP-MECY is exciting. Positive cytologic washings at the 6-month laparoscopic evaluation were highly predictive that residual disease would be found at the 1-year second-look surgery. Only one patient with positive peritoneal cytology after 6 months of treatment was found to have a negative second-look after 1 year of therapy.