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 showed that gemcitabine/cisplatin is as effective and much less toxic. In an attempt to farther 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. Many such phase II trials have been performed. Two small randomized trials comparing cisplatin-based regimens to carboplatin-based regimens have been published.[13,14] One trial reported a lower complete response rate, while the other trial reported shorter disease-specific survival with the carboplatin-based regimen. However, these studies were underpowered, and the one that showed a disease-specific survival difference included an anthracycline in the cisplatin arm but not in the carboplatin arm. A phase III trial (DeSantis et al) showed that for patients who are older and have Performance Status of 21 or higher, the cisplatin containing regimen was inferior, probably because iof cisplatin toxicity. On the other hand, respones rates were low in both arms, suggesting that overall any chemotherapy was not beneficial. NCCN says that cisplatin should be used for patients with normal renal function and PS >
<2. It implies that carboplatin may be acceptable but recommends split dose cisplatin, while stating that efficacy of such dose modification is not known
Nogué-Aliguer M, Carles J, Arrivi A, et al. Gemcitabine and carboplatin in advanced transitional cell carcinoma of the urinary tract.An alternative therapy. Cancer 2003;97:2180-2186.
Bamias A, Moulopoulos LA, Koutras A, Aravantinos G, Fountzilas G, Pectasides D, Kastritis E, Gika D, Skarlos D, Linardou H, Kalofonos HP, Dimopoulos MA.The combination of gemcitabine and carboplatin as first-line treatment in patients with advanced urothelial carcinoma. A Phase II study of the Hellenic Cooperative Oncology Group.
Cancer. 2006 Jan 15;106(2):297-303.
Petrioli R, Frediani B, Manganelli A, Barbanti G, De Capua B, De Lauretis A, Salvestrini F, Mondillo S, Francini G.Comparison between a cisplatin-containing regimen and a carboplatin-containing regimen for recurrent or metastatic bladder cancer patients. A randomized phase II Cancer. 1996 Jan 15;77(2):344-51.
Maria De Santis, Joaquim Bellmunt, Graham Mead, J. Martijn Kerst, Michael Leahy, Pablo Maroto, Iwona Skoneczna, Sandrine Marreaud, Ronald de Wit and Richard Sylvester Randomized Phase II/III Trial Assessing Gemcitabine/ Carboplatin and Methotrexate/Carboplatin/Vinblastine in Patients With Advanced Urothelial Cancer “Unfit” for Cisplatin-Based Chemotherapy: Phase II—Results of EORTC Study 30986 JCO November 20, 2009 vol. 27
Vaughn DJ: Chemotherapeutic options for cisplatin-ineligible patients with advanced carcinoma of the urothelium. Cancer Treat Rev 34 (4): 328-38, 2008.
NCCN BCL-6, 2014