Invest New Drugs (2008) 26:151–158 DOI 10.1007/s10637-007-9111-2
PHASE I STUDIES
Phase I study of a 3-drug regimen of gemcitabine/cisplatin/ pemetrexed in patients with metastatic transitional cell carcinoma of the urothelium Thomas E. Hutson & Svetislava Vukelja & Daniel Atienza & Sanjay Awasthi & Robert Delaune & Margaret Deutsch & Philip Y. Dien & Thomas F. Gregory & Michael J. Kolodziej & Joseph J. Muscato & Robert N. Raju & Robert L. Ruxer Jr & Stephanie Mull & Des Ilegbodu & Karen Hood & Steven Nicol & William Berry
Received: 19 September 2007 / Accepted: 28 December 2007 / Published online: 31 January 2008 # Springer Science + Business Media, LLC 2008
Summary Objectives: Gemcitabine (G) plus cisplatin (C) is standard care for metastatic transitional cell carcinoma (TCC) of the urothelium. Pemetrexed (P), alone or in combination with G, is active in metastatic TCC. However, the safety and efficacy of P combined with GC therapy is
unknown. This phase I trial was designed to determine the maximum tolerated dose (MTD) of GC followed by P + G in patients with metastatic TCC. Methods: Cohorts of 3 to 6 patients received escalating doses 28-day cycles (maximum 6 cycles): G 800–1,000 mg/m2 on days 1 and 15; P 400–
T. E. Hutson (*) US Oncology Research, Inc., Genitourinary Oncology Program, Houston, TX, USA e-mail:
[email protected]
R. Delaune Minnesota Oncology Hematology, Mapplewood, MN, USA
T. E. Hutson Baylor-Sammons Cancer Center, 3535 Worth Street, Suite 185, Dallas, TX 75246, USA T. E. Hutson Texas Oncology, P.A., Dallas, TX, USA S. Vukelja : D. Atienza : S. Awasthi : R. Delaune : M. Deutsch : P. Y. Dien : T. F. Gregory : M. J. Kolodziej : J. J. Muscato : R. N. Raju : R. L. Ruxer Jr : S. Mull : D. Ilegbodu : W. Berry US Oncology Research, Inc., Houston, TX, USA
P. Y. Dien Minnesota Oncology Hematology, Burnsville, MN, USA M. J. Kolodziej New York Oncology Hematology-Albany Regional Cancer Center, Albany, NY, USA J. J. Muscato Missouri Center Associates, Columbia, MO, USA R. N. Raju Dayton Oncology and Hematology-Kettering, Kettering, OH, USA
S. Vukelja : M. Deutsch : T. F. Gregory Tyler Cancer Center and Texas Oncology, P.A., Tyler, TX, USA
R. L. Ruxer Jr Texas Oncology, P.A., Fort Worth, TX, USA
D. Atienza Virginia Oncology Associates-Lake Wright, Norfolk, VA, USA
K. Hood : S. Nicol Eli Lilly and Company, Indianapolis, IN, USA
S. Awasthi Texas Cancer Center-Arlington South and Texas Oncology, P.A., Arlington, TX, USA
W. Berry Raleigh Hematology-Oncology Associates, P.A., Raleigh, NC, USA
DO09111; No of Pages
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500 mg/m2 on day 15; and C 50–70 mg/m2 on day 1. All patients received folic acid, vitamin B12, and full supportive care. The 3+3 standard phase I escalation rule was used to determine MTD. Results: Fifteen patients registered: 13/15 white males; median age 70 years (range, 53–82); 11/15 had KPS≥90. At dose level 0, 2/4 patients experienced unrelated DLTs, and 1 patient was replaced (completed 100×109/L, and hemoglobin of >9.0 g/dL; and adequate hepatic and renal function (bilirubin
