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Phase I study of a 3-drug regimen of gemcitabine/cisplatin/pemetrexed in patients with metastatic transitional cell carcinoma of the urothelium.

Publication ,  Journal Article
Hutson, TE; Vukelja, S; Atienza, D; Awasthi, S; Delaune, R; Deutsch, M; Dien, PY; Gregory, TF; Kolodziej, MJ; Muscato, JJ; Raju, RN; Ruxer, RL ...
Published in: Investigational new drugs
April 2008

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.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 400-500 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.Fifteen patients registered: 13/15 white males; median age 70 years (range, 53-82); 11/15 had KPS>or=90. At dose level 0, 2/4 patients experienced unrelated DLTs, and 1 patient was replaced (completed<1 cycle). Dose escalation proceeded to dose level 1. At level 1, 4/6 patients experienced DLTs; dosing decreased to level 0 and 4/5 patients experienced DLTs. The MTD was not determined. The 2 patients that completed 6 cycles both had partial responses. Grades 3-4 hematologic toxicities included neutropenia (60%), leukopenia (20%), and febrile neutropenia (13%).Adding P to the standard GC regimen as first-line therapy for metastatic TCC produced no benefit. The MTD exceeded therapeutic gemcitabine and cisplatin doses for urothelial cancer and thus the study was aborted.

Published In

Investigational new drugs

DOI

EISSN

1573-0646

ISSN

0167-6997

Publication Date

April 2008

Volume

26

Issue

2

Start / End Page

151 / 158

Related Subject Headings

  • Vitamin B Complex
  • Vitamin B 12
  • Urothelium
  • Urinary Bladder Neoplasms
  • Treatment Outcome
  • Pemetrexed
  • Oncology & Carcinogenesis
  • Neoplasm Metastasis
  • Middle Aged
  • Maximum Tolerated Dose
 

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Hutson, T. E., Vukelja, S., Atienza, D., Awasthi, S., Delaune, R., Deutsch, M., … Berry, W. (2008). Phase I study of a 3-drug regimen of gemcitabine/cisplatin/pemetrexed in patients with metastatic transitional cell carcinoma of the urothelium. Investigational New Drugs, 26(2), 151–158. https://doi.org/10.1007/s10637-007-9111-2
Hutson, Thomas E., Svetislava Vukelja, Daniel Atienza, Sanjay Awasthi, Robert Delaune, Margaret Deutsch, Philip Y. Dien, et al. “Phase I study of a 3-drug regimen of gemcitabine/cisplatin/pemetrexed in patients with metastatic transitional cell carcinoma of the urothelium.Investigational New Drugs 26, no. 2 (April 2008): 151–58. https://doi.org/10.1007/s10637-007-9111-2.
Hutson TE, Vukelja S, Atienza D, Awasthi S, Delaune R, Deutsch M, et al. Phase I study of a 3-drug regimen of gemcitabine/cisplatin/pemetrexed in patients with metastatic transitional cell carcinoma of the urothelium. Investigational new drugs. 2008 Apr;26(2):151–8.
Hutson, Thomas E., et al. “Phase I study of a 3-drug regimen of gemcitabine/cisplatin/pemetrexed in patients with metastatic transitional cell carcinoma of the urothelium.Investigational New Drugs, vol. 26, no. 2, Apr. 2008, pp. 151–58. Epmc, doi:10.1007/s10637-007-9111-2.
Hutson TE, Vukelja S, Atienza D, Awasthi S, Delaune R, Deutsch M, Dien PY, Gregory TF, Kolodziej MJ, Muscato JJ, Raju RN, Ruxer RL, Mull S, Ilegbodu D, Hood K, Nicol S, Berry W. Phase I study of a 3-drug regimen of gemcitabine/cisplatin/pemetrexed in patients with metastatic transitional cell carcinoma of the urothelium. Investigational new drugs. 2008 Apr;26(2):151–158.
Journal cover image

Published In

Investigational new drugs

DOI

EISSN

1573-0646

ISSN

0167-6997

Publication Date

April 2008

Volume

26

Issue

2

Start / End Page

151 / 158

Related Subject Headings

  • Vitamin B Complex
  • Vitamin B 12
  • Urothelium
  • Urinary Bladder Neoplasms
  • Treatment Outcome
  • Pemetrexed
  • Oncology & Carcinogenesis
  • Neoplasm Metastasis
  • Middle Aged
  • Maximum Tolerated Dose