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Clin Genitourin Cancer. 2018 Dec;16(6):437-444.e6. doi: 10.1016/j.clgc.2018.07.021. Epub 2018 Jul 29.

Multicenter Phase 2 Trial of Gemcitabine, Carboplatin, and Sorafenib in Patients With Metastatic or Unresectable Transitional-Cell Carcinoma.

Author information

1
Yale Cancer Center, New Haven, CT.
2
Department of Medicine, Rutgers Cancer Institute of New Jersey, NJ.
3
Ohio State University Cancer Center, OH.
4
St Francis Hospital and Medical Center, Hartford, CT.
5
Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA.
6
Department of Medicine, Rutgers Cancer Institute of New Jersey, NJ. Electronic address: mehnerja@cinj.rutgers.edu.

Abstract

BACKGROUND:

Sorafenib, an oral tyrosine kinase inhibitor, may enhance the antitumor activity of platinum-based chemotherapy in transitional-cell carcinoma. This study investigated the safety and clinical outcome of adding sorafenib to gemcitabine and carboplatin for patients with advanced transitional-cell carcinoma.

PATIENTS AND METHODS:

Subjects with metastatic or unresectable chemotherapy-naive TCC with Eastern Cooperative Oncology Group performance status 0 or 1 received gemcitabine (1000 mg/m2 on days 1 and 8) and carboplatin (area under the curve of 5 on day 1) with sorafenib (400 mg 2 times a day on days 2-19 every 21 days) for 6 cycles. Subjects with stable disease or partial or complete response continued to receive sorafenib until disease progression. The primary end point was progression-free survival (PFS) at 5 months with a secondary end point of response (partial or complete).

RESULTS:

Seventeen subjects were enrolled. The median number of cycles of gemcitabine and carboplatin with sorafenib provided was 4.4. A total of 15, 5, and 8 subjects required reductions of gemcitabine, carboplatin, and sorafenib, respectively. Thirteen subjects (76%) required multiple dose reductions. Eleven subjects (65%) were free of progression at 5 months. The overall response rate was 54% (95% confidence interval [CI], 0.28-077), with 4 patients experiencing complete response (24%; 95% CI, 0.07-0.50) and 5 partial response (29%; 95% CI, 0.10-0.56); 7 subjects (41%) had stable disease. Median PFS was 9.5 months (95% CI, 0.43-1.26), and median overall survival was 25.2 months (95% CI, 0.96-5.65). One-year PFS was 31%, and 1-year overall survival was 72%. Eleven subjects (65%) discontinued treatment because of toxicity. There were no toxic deaths.

CONCLUSION:

Gemcitabine and carboplatin with sorafenib showed clinical activity in advanced TCC, with some prolonged progression-free intervals. However, gemcitabine and carboplatin with sorafenib was associated with significant toxicity, causing discontinuation of therapy in most patients.

KEYWORDS:

Chemotherapy; First line; TCC; Tyrosine kinase inhibitor; Urothelial carcinoma

PMID:
30177237
DOI:
10.1016/j.clgc.2018.07.021
[Indexed for MEDLINE]

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