THE OPTIMIZATION OF CARBOPLATIN DOSE IN CARBOPLATIN, ETOPOSIDE AND BLEOMYCIN COMBINATION CHEMOTHERAPY FOR GOOD PROGNOSIS METASTATIC NONSEMINOMATOUS GERM-CELL TUMORS OF THE TESTIS

An analysis of carboplatin dose response was performed in 121 patients with good prognosis metastatic nonseminomatous germ cell tumours (NSGCT) of the testis, referred to the Royal Marsden Hospital since 1984, who had been given combination carboplatin, etoposide and bleomycin (CEB) chemotherapy. With a median follow-up of 40 months (range: 7 to 85 months) nine patients (7%) have failed CEB. Carboplatin dose was analysed in all patients using body surface area (BSA) to derive a carboplatin dose per metre squared (mg/m2) and by calculation of a predicted serum concentration chi-time (AUC: area under the curve) derived from the glomerular filtration rate (GFR), using the formula; Dose = AUC(GFR + 25). At a carboplatin dose of 400 mg/m2 or greater 2 out of 58 patients (3.4%) failed treatment while 7 out of 63 patients (11%) who received a dose less than this failed (p > 0.1). At an AUC of 5.0 mg.min/ml or greater, 2 out of 74 patients (2.7%) failed while 7 out of 47 patients (14.9%) who had an AUC less than this failed (p < 0.05). There was evidence for a dose/response relationship at relatively low doses and the failure rate rose to 26% for doses less than 4.5 mg.min/ml (p < 0.001) or 15.6% for doses less than 350 mg/m2 (p > 0.1). In view of the more precise determination of toxicity and efficacy it is recommended that carboplatin dose be based on the GFR.