Taxol and carboplatin for bladder cancer – pro

The standard treatment for advanced bladder cancer is the chemotherapy combination consisting of cisplatin (Platinol®), methotrexate, Velban® (vinblastine) and doxorubicin (Adriamycin®), referred to as M-VAC. However, M-VAC is associated with side effects and are particularly difficult to tolerate for patients who have impaired renal function and/or are elderly. Researchers have been evaluating different chemotherapy combinations for the treatment of advanced bladder cancer in patients who are not able to tolerate M-VAC. A randomized study shwoed that gemcitabine/cisplatin is as effective and much less toxic. In an attempt to fartehr reduce toxicity, carboplatin has been substituted for cisplatin. That the two drugs are very similar and carboplatin has been able to substitute for cisplatin in many tumor types.

Paclitaxel demonstrates significant single-agent activity in advanced urothelial carcinoma. A phase II trial conducted in 1994 demonstrated that paclitaxel (Taxol) was effective in locally advanced or metastatic transitional cell carcinoma of the urothelium with a complete response rate of 27%. Due to the lack of nephrotoxicity, and the ability to administer Taxol to patients with renal insufficiency, new regimens could provide potential advantages over the standard cisplatin-based regimens. Paclitaxel/carboplatin is an active and tolerable outpatient chemotherapy treatment regimen for these patients. This regimen has been studied in several phase II trials with response rates ranging from 14 to 65%. Preliminary results suggest that the combination of paclitaxel and carboplatin as first-line therapy compared well with the outcome after MVAC, and with less toxicity.

A phase III trial conducted by ECOG compared MVAC with paclitaxelplus carboplatin. Patients with previously untreated metastatic TCC were randomized to either standard MVAC or paclitaxel (225mg/m2) plus carboplatin (AUC 6) administered every 21 days.After 2.5 years, the study was terminated due to slow accrual.Of the planned 330 patients, only 85 were enrolled. Comparedwith carboplatin/paclitaxel (CP), patients treated with MVAC had more severe myelosuppression, mucositis, and renal toxicity.Interestingly, a quality-of-life instrument revealed no significant differences between the two arms. At a median follow-up of 32.5months, there was no significant difference in response rate(35.9% MVAC versus 28.2% CP, p = .34) or median survival (15.4months MVAC versus 13.8 months CP, p = .41) between the two arms. However, definitive conclusions are not possible given that the trial was severely underpowered.

Ongoing trials are comparing paclitaxel/carboplatin with M-VAC (methotrexate, vinblastine, doxorubicin, cisplatin) in both the advanced disease and adjuvant settings.

Galsky MD. The role of taxanes in the management of bladder cancer.Oncologist. 2005 Nov-Dec;10(10):792-8.

F.A. Yafi  et al, First- and second-line therapy for metastatic urothelial carcinoma of the bladder
Oncology Vol 18, No 1 (2011)

Galsky MD. The role of taxanes in the management of bladder cancer.Oncologist. 2005 Nov-Dec;10(10):792-8.

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