Schedule and dosage modification of a cyclophosphamide, hexamethylmelamine, doxorubicin, cisplatin combination chemotherapy regimen for refractory ovarian cancer.

A cyclophosphamide, hexamethylmelamine, doxorubicin and cisplatin (CHAP II) regimen produced median survival of 15 and 17 months. All patients had prior chemotherapy, 26 with cisplatin in the former group, and 27 without cisplatin in the latter group. Treatment employed both a novel sequential schedule of cisplatin (usually in the evening) 24 h before cyclophosphamide-doxorubicin and novel stepwise escalation, first of doxorubicin, then of hexamethylmelamine until either nadir white blood counts fell to 1000-1500/mm3 or platelets to 75,000-100,000/mm3. Compared to prior Mount Sinai experience: (i) survival was significantly improved; (ii) with and without prior cisplatin, response rates approached a significant improvement, 12% and 29% complete and 24% and 35% partial. Five of seven additional patients with progression during unmaintained remission also responded, two with pathologically complete remissions. Findings suggest: (i) the importance of maximum dose intensity in ovarian cancer treatment; (ii) the responsiveness of patients failing first line treatment to dose intensive treatment; (iii) the possible importance of schedule, and sequential or circadian timing of cisplatin, and other drugs; (iv) and testing revised clinical criteria of resistance to drugs.