Comparative toxicity of cisplatin, carboplatin (CBDCA) and iproplatin (CHIP) in combination with cyclophosphamide in patients with advanced epithelial ovarian cancer

Sixty patients with FIGO stage IIb, IIc, III and IV ovarian cancer were entered into a randomized Phase III study of cyclophosphamide 600 mg/m 2 with cisplatin 100 mg/m 2 , iproplatin 240 mg/m 2 or carboplatin 300 mg/m 2 . Dose modifications were made according to renal function and myelotoxicity. The arms containing carboplatin (CBDCA) and iproplatin (CHIP) were not shown to be significantly different from the cisplatin containing arm with regard to response rate, duration of response and survival. Subjective toxicity showed that cisplatin and cyclophosphamide therapy was associated with more nausea and vomiting ( P = 0.0005). The duration of vomiting showed a significant increase with successive courses of chemotherapy for the cisplatin containing arm only ( P < 0.003). The cyclophosphamide/CHIP combination caused significantly more diarrhoea ( P < 0.0006). Alopecia was more severe ( P < 0.02), and neurotoxicity was more common, in patients who received cyclophosphamide and cisplatin (paraesthesiae P = 0.0007, tinnitus P < 0.00005, deafness P = 0.0018). All three combinations caused cumulative toxicity on haemoglobin (Hb) ( P < 0.001 for each treatment), leukocyte count (WCC) ( P < 0.0005 for each treatment), and platelet count ( P < 0.0005 for each treatment). The degree of fall in Hb for each course of therapy was greater in the cisplatin containing arm compared with the CHIP and CBDCA arms which were not significantly different from each other ( P = 0.0005). For WCC the cisplatin/cyclophosphamide regimen was significantly less toxic than CHIP/cyclophosphamide, with CBDCA/cyclophosphamide falling between the two and not being significantly different from either ( P = 0.0005). The CHIP containing arm caused more thrombocytopenia than the other arms which were of equal toxicity ( P < 0.0005). Serum creatinine showed a gradual significant overall rise with each course of cisplatin/cyclophosphamide therapy ( P < 0.0005), whereas the CBDCA arm showed no change and the CHIP arm showed a small fall in serum creatinine after most courses of therapy. This study showed that CHIP or CBDCA in combination with cyclophosphamide was less toxic than cisplatin/cyclophosphamide therapy with regard to alopecia, degree and duration of nausea and vomiting, renal toxicity, neurotoxicity and anaemia. The CHIP/cyclophosphamide regimen caused more thrombocytopenia and diarrhoea. The CHIP and CBDCA containing arms caused more leukopenia than the cisplatin containing regimen. Ei