CARBOPLATIN AND UROTHELIAL TUMORS

The prognosis of advanced-stage bladder cancer is poor. Chemotherapy, particularly regimens including platinum salts, appears to increase su rvival moderately but at the cost of severe, mainly renal toxicity. Pl atinum is a major factor in this toxicity, and new platinum salts (chi efly carboplatin) have therefore been developed. Carboplatin has no re nal toxicity at usual doses, and its use does not require concomitant hyperhydration. Its gastrointestinal, otologic, and general tolerabili ty is excellent. In contrast, most patients develop thrombocytopenia, which can be important, but which is always transitory. The platelet c ount reaches its nadir (grade 2 or 3) at around day 20, and the leukoc yte nadir (grade 2 or 3) occurs about day 19. Anemia is rare. The lite rature on the use of carboplatin for the treatment of advanced-stage u rothelial tumors is reviewed. Carboplatin is used at doses varying bet ween 200 and 400 mg/m(2), administered in 28-day courses. Dose adjustm ent is based on serum creatinine level, creatinine clearance, nadir bl ood cell levels, or previous treatment, reflecting the wide disparity between different studies. Used alone, carboplatin achieved objective responses (ORs) in 14% of patients (3% complete responses, CRs, and 11 % partial responses, PRs) in a total group of 327 patients included in 13 trials. In polychemotherapy various combinations of carboplatin wi th other agents have been reported, most frequently carboplatin/methot rexate/vinblastine; the OR rate was 63% (CR rate 19% and PR rate 44%) among 88 patients in four studies. These results confirm the relative efficacy of carboplatin in the treatment of advanced-stage urothelial tumors, particularly when it is combined with other agents. Its effica cy is similar to that of cisplatin, but it is far less toxic. A prospe ctive, comparative trial will be necessary to confirm these data. The pharmacokinetic behaviors of the two platinum salts are markedly diffe rent, as carboplatin does not undergo tubular metabolism. The efficacy of carboplatin could be optimized by adapting the dosage to the glome rular filtration rate, which is a more accurate method than extrapolat ion from the serum creatinine or creatinine clearance values. This has been shown in the case of nonseminomatous germ cell tumors. Calculati on of the optimum carboplatin dose should now be applied to urothelial tumors. The general and renal tolerability of a platinum salt is an i mportant element of choice when the efficacies are equivalent. These c onsiderations fully warrant further clinical trials of carboplatin.