Phase I trial of carboplatin-cyclophosphamide and iproplatin-cyclophosphamide in advanced ovarian cancer: a Southwest Oncology Group study

The Southwest Oncology Group has carried out a phase I clinical trial of carboplatin plus cyclophosphamide and iproplatin plus cyclophosphamide in 20 patients with stages III and IV ovarian cancer prior to initiating a phase III trial to compare these platinum analogcyclophosphamide combinations with standard cisplatin-cyclophosphamide therapy. Myelosuppression proved the dose-limiting toxicity of both the carboplatin (300 mg/m²) plus cyclophosphamide (600 mg/m²) and iproplatin (180 mg/m²) plus cyclophosphamide (600 mg/m²) regimens. Evaluating up to six courses of therapy (repeated at 4-week intervals), the median nadir WBC and platelet counts associated with carboplatin-cyclophosphamide therapy were 1800 (range, 900-4000) and 69 000 per μl, respectively, and those associated with iproplatin-cyclophosphamide therapy were 1400 (1100-1600) and 140 000 per μl, respectively. Although the starting doses of carboplatin and iproplatin required a median decrease of 25%, the median doses of each administered through six courses of therapy were 300 and 180 mg/m², respectively. Neither nephrotoxicity nor neuropathy were experienced by the patients, but mild to moderate nausea and vomiting occurred in more than 75% of those treated with either drug combination. Alopecia of mild to severe degree was observed in 40% of patients. Although the results of this phase I trial are still preliminary, we can recommend for future phase III trials 300 mg/m² carboplatin and 180 mg/m² iproplatin when combined with 600 mg/m² cyclophosphamide repeated at 4-week intervals for six treatment courses.