Originally published as JCO Early Release 10.1200/JCO.2008.21.2241 on July 27 2009

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Final Results of Sequential Doxorubicin Plus Gemcitabine and Ifosfamide, Paclitaxel, and Cisplatin Chemotherapy in Patients With Metastatic or Locally Advanced Transitional Cell Carcinoma of the Urothelium

From the Genitourinary Oncology Service, Division of Solid Tumor Oncology, Department of Medicine; Department of Radiology; and Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center; and Weill Cornell Medical College of Cornell University; Department of Medicine, New York Presbyterian Hospital, New York, NY; and Division of Urology, Hospital das Clínicas, University of São Paulo and Department of Medical Oncology, Hospital Sírio-Libanês, São Paulo-SP-Brazil.

Corresponding author: Matthew I. Milowsky, MD, Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; e-mail: milowskm{at}mskcc.org.

Purpose Sequential chemotherapy with doxorubicin and gemcitabine (AG) followed by ifosfamide, paclitaxel, and cisplatin (ITP) was previously demonstrated to be well tolerated in patients with advanced transitional cell carcinoma (TCC). This study sought to evaluate the efficacy and to additionally define toxicity.

Patients and Methods Sixty patients with advanced TCC received AG every 2 weeks for five or six cycles followed by ITP every 21 days for four cycles. Granulocyte colony-stimulating factor was given between cycles.

Results Myelosuppression was seen with 68% of patients who experienced grades 3 to 4 neutropenia and with 25% who experienced febrile neutropenia. Grade 3 or greater nonhematologic toxicities were infrequent. Forty (73%) of 55 evaluable patients (95% CI, 59% to 84%) demonstrated a major response (complete, n = 19; partial, n = 21) and had a median response duration of 11.3 months (range, 1.7 to 105.6 months). Twenty-seven (79%) of 34 patients with locally advanced disease (ie, T4, N0, M0) or with regional lymph node involvement (ie, T3-4, N1, M0) and 10 (56%) of 18 patients with distant metastases achieved a major response. The median progression-free survival was 12.1 months (95% CI, 9.0 to 14.8 months), and the median overall survival was 16.4 months (95% CI, 14.0 to 22.5 months). At a median follow-up of 76.4 months, seven (11.7%) patients remain alive, and all were disease free.

Conclusion AG plus ITP is an active regimen in previously untreated patients with advanced TCC; however, it is associated with toxicity and does not clearly offer a benefit compared with other nonsequential, cisplatin-based regimens.

Supported in part by Eli Lilly and Bristol-Myers Squibb.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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