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 analog-cyclophosphamide 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 microliter, respectively, and those associated with iproplatin-cyclophosphamide therapy were 1400 (1100-1600) and 140 000 per microliter, 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 a 4-week intervals for six treatment courses.
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D016190:Carboplatin; D002986:Clinical Trials as Topic; D003520:Cyclophosphamide / Q000008:administration & dosage; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010051:Ovarian Neoplasms / Q000188:drug therapy*
D009944:Organoplatinum Compounds; C023359:iproplatin; D003520:Cyclophosphamide; D016190:Carboplatin