Carboplatin and Urothelial Tumors

Abstract

The prognosis of advanced-stage bladder cancer is poor. Chemotherapy, particularly regimens including platinum salts, appears to increase survival moderately but at the cost of severe, mainly renal toxicity. Platinum is a major factor in this toxicity, and new platinum salts (chiefly carboplatin) have therefore been developed. Carboplatin has no renal toxicity at usual doses, and its use does not require concomitant hyperhydration. Its gastrointestinal, otologic, and general tolerability is excellent. In contrast, most patients develop thrombocytopenia, which can be important, but which is always transitory. The platelet count reaches its nadir (grade 2 or 3) at around day 20, and the leukocyte nadir (grade 2 or 3) occurs about day 19. Anemia is rare. The literature on the use of carboplatin for the treatment of advanced-stage urothelial tumors is reviewed. Carboplatin is used at doses varying between 200 and 400 mg/m², administered in 28-day courses. Dose adjustment is based on serum creatinine level, creatinine clearance, nadir blood 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 with other agents have been reported, most frequently carbopla-tin/methotrexate/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 efficacy is similar to that of cisplatin, but it is far less toxic. A prospective, comparative trial will be necessary to confirm these data. The pharmacokinetic behaviors of the two platinum salts are markedly different, as carboplatin does not undergo tubular metabolism. The efficacy of carboplatin could be optimized by adapting the dosage to the glomerular filtration rate, which is a more accurate method than extrapolation from the serum creatinine or creatinine clearance values. This has been shown in the case of nonseminomatous germ cell tumors. Calculation of the optimum carboplatin dose should now be applied to urothelial tumors. The general and renal tolerability of a platinum salt is an important element of choice when the efficacies are equivalent. These considerations fully warrant further clinical trials of carboplatin.

Carboplatin-based versus cisplatin-based chemotherapy in the treatment of surgically incurable advanced bladder carcinoma

“…have shown results not significantly different than Study Design those for single agent cisplatin, with overlapping in the This was a prospective, randomized trial comparing confidence intervals, 16 the most common substitution M-VAC with M-CAVI in the treatment of patients with has been carboplatin for cisplatin. We have previously advanced bladder carcinoma.…”

“…Moreover, the analysis at 5 years showed that advanced bladder carcinoma, carboplatin has yielded the M-VAC arm was associated with a significantly results equivalent to those for single agent cisplatin. 16 So far, no randomized trial comparing a regimen superior survival. Thus, the trial was terminated early.…”

The Role of Perioperative Chemotherapy in the Treatment of Urothelial Cancer

“…Other efforts have focused on developing the combination of carboplatin and paclitaxel as adjuvant therapy [25]. Both carboplatin and paclitaxel have shown single-agent activity in phase II studies [53,54] but as a combination have not been proven to be superior to M-VAC [23]. Alternatively, high-dose M-VAC with growth factor support has been postulated to be a reasonable area of investigation in the neoadjuvant setting in light of a shorter cycle length (14 days), less toxicity, and higher response rates relative to M-VAC, although no difference in survival was seen in patients with advanced disease [21].…”

New Perspectives on an Old Friend: Optimizing Carboplatin for the Treatment of Solid Tumors

“…In urothelial cancer, single-agent carboplatin produces only low response rates of approximately 15%. However, when combined with methotrexate, much higher response rates are attained (36%), toxicity is manageable, and median survival times exceed one year [172,173]. Carboplatin at an AUC of 6 also has been combined with a 3-h infusion of paclitaxel in a phase I/II trial in patients with advanced bladder cancer [174].…”