A Randomized Study of High-Dose versus Low-Dose cis-Platinum Combined with Cyclophosphamide in the Treatment of Advanced Ovarian Cancer

Abstract

A randomized clinical study of patients with advanced epithelial ovarian cancer after debulking surgery showed that high-dose (120 mg/m²) cis-platinum (DDP) in combination with cyclophosphamide (600 mg/m²) had a significantly higher response and survival rate than the low-dose DDP (60 mg/m²) and cyclophosphamide combination. The 3-year actuarial survival rate of the high-dose group was 60% and that of the low-dose group was 30%. Though moderate to severe marrow toxicity was evident in 80% of the patients in the high-dose group and 40% of the low-dose group, no serious sepsis or death developed as a result of the marrow depression. Mild neurotoxicity was observed in 55% of the patients in the high-dose group and only 20% in the low-dose group. Mild nephrotoxicity was seen in 25 and 17% of patients in the high- and low-dose groups, respectively. It was concluded that the 120 mg/m² dose DDP and cyclophosphamide combination should be used in the treatment of carcinoma of the ovary in spite of its toxicities. However, it should only be used in institutions with supportive facilities in the management of patients with severe marrow depression.

Resistance to chemotherapy in advanced ovarian cancer: mechanisms and current strategies

“…The earliest of these studies (Ngan et al , 1989) was carried out in 50 assessable patients with debulked advanced epithelial ovarian cancer, and showed 3-year actuarial survival rates of 60 and 30% for high-dose (120 mg m −2 ) and low-dose (60 mg m −2 ) cisplatin, respectively (both given every 3–4 weeks in combination with cyclophosphamide 600 mg m −2 ). Notwithstanding this impressive difference between groups, some doubt has been attached to the results of this study because of the small size of the patient cohort studied and because baseline disease characteristics were not fully characterised.…”

Protocol Development for Ovarian Cancer Treatment in Kenya: A Brief Report

“…Two studies compared higher (100Y120 mg/m 2 ) and lower doses (50Y60 mg/m 2 ) of cisplatin in combination with cyclophosphamide (600Y750 mg/m 2 ). 8,9 Although both RCTs reported that a higher dose of cisplatin improved survival and response rate, they also reported significant increases in myelosuppression, neurotoxicity, and ototoxicity. Sizes of both trials were small (50 and 165 patients), and one of them ended early.…”

Remaining controversies in the upfront management of advanced ovarian cancer

“…Only three small randomized trials have, so far, showed a significant survival benefit for higher doses of CDDP (27,31,32) . The largest of these trials was prematurely closed after the interim analysis, at 2 years of follow-up, showed an increased median survival with high-dose CDDP (114 versus 69 weeks; P ¼ 0.0008; HR ¼ 0.68).…”