Elsevier

Urology

Volume 69, Issue 2, February 2007, Pages 255-259
Urology

Adult urology
Prospective Trial of Ifosfamide, Paclitaxel, and Cisplatin in Patients with Advanced Non-transitional Cell Carcinoma of the Urothelial Tract

This study was presented in part at the 2006 American Society of Clinical Oncology Annual Meeting, Atlanta, Georgia, June 2006.
https://doi.org/10.1016/j.urology.2006.10.029Get rights and content

Objectives

Non-transitional cell carcinomas account for 5% to 10% of urothelial tract tumors and are each characterized by unique demographics, risk factors, and patterns of spread. A unifying feature of these malignancies is their aggressive course and poor outcome with standard chemotherapeutic regimens. Given the rarity of these tumors, no prospective data are available to guide management.

Methods

Patients with unresectable/metastatic adenocarcinoma or squamous cell, small cell, sarcomatoid, or poorly differentiated carcinoma of the urothelial tract were eligible for enrollment. Treatment consisted of paclitaxel 200 mg/m2 intravenously on day 1, cisplatin 70 mg/m2 intravenously on day 1, ifosfamide 1500 mg/m2 intravenously on days 1 to 3 plus mesna. Granulocyte colony-stimulating factor was administered with each cycle. The treatment was started again every 3 to 4 weeks for a maximum of six cycles.

Results

A total of 20 patients were enrolled. They had the following histologic types: adenocarcinoma in 11, squamous cell carcinoma in 8, and small cell carcinoma in 1. Patients received a median of four cycles (range one to six). The treatment was generally well tolerated, and the toxicity was predominantly hematologic. Overall, 7 (35%) of 20 patients (95% confidence interval 15% to 59%) achieved a major response (3 partial and 4 complete). The median survival for patients with adenocarcinoma was 24.8 months (95% confidence interval 10.2 to 32.3), and for those with squamous cell carcinoma it was 8.9 months (95% confidence interval 5.4 to not yet reached).

Conclusions

The results of our study have shown that this regimen (ifosfamide, paclitaxel, and cisplatin) is active in patients with advanced non-transitional cell carcinoma of the urothelial tract. To our knowledge, this is the first prospective study of a chemotherapeutic regimen in this patient population.

Section snippets

Patient Population

To be eligible for this study, all patients were required to have measurable or evaluable non-TCC of the urothelial tract. Measurable disease included unresectable or metastatic urothelial tract tumors that were bi-dimensionally measurable on x-ray, cross-sectional imaging, or physical examination. Evaluable disease was restricted to unresectable bladder tumors that could be evaluated for response by cystoscopy and examination under anesthesia. Pathologic confirmation was required at Memorial

Patient Characteristics

The patient characteristics are detailed in Table 2. Twenty patients were enrolled from February 1997 to September 2004. Of these 20 patients, 11 had adenocarcinoma, 8 had squamous cell carcinoma, and 1 had small cell carcinoma. Of the 11 patients with adenocarcinoma, 6 had tumors of urachal origin. Of the 20 patients, 14 had metastatic disease (70%) and 6 had unresectable primary tumors. Although the median age of those enrolled was 57 years, 35% of the patients were 50 years old or older at

Comment

To our knowledge, this is the first prospective trial exploring the use of a specific chemotherapy regimen for the treatment of patients with advanced/metastatic (nonbilharzial) non-TCC of the bladder. The results of this study have demonstrated the safety and activity of ITP in patients with squamous cell carcinoma, small cell carcinoma, and adenocarcinoma of the urothelial tract. Furthermore, our results have revealed that long-term disease-free survival is possible in a select subgroup of

Conclusions

Larger trials are desirable to confirm, and improve on, our results. However, even in the cooperative group setting, trials in patients with rare malignancies are difficult to complete, taking several years to accrue a small number of patients. Innovative collaborative efforts are likely needed, such as those proved successful in the study of other rare malignancies,13 to make meaningful advances in the management of non-TCCs of the urothelial tract. Currently, in the absence of a prospective

References (13)

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    However, Galsky et al. conducted a prospective phase II trial of ifosfamide, paclitaxel, and cisplatin in advanced non-UC histologies including 8 patients with SCC. Two of these patients achieved radiographic CR, one had stable disease (SD), and 5 had progressive disease (PD) as their best clinical response; median OS was 8.9 months [28]. In advanced bilharzial SCC, a phase II study of gemcitabine and cisplatin yielded an objective response rate (ORR) of 55% including 8 (24%) CRs and 10 (30%) PRs [29].

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D. F. Bajorin has been a paid consultant and received research funding in the past from Bristol-Myers Squibb.

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