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A phase II trial of R115777, an oral farnesyl transferase inhibitor, in patients with advanced urothelial tract transitional cell carcinoma
Author(s) -
Rosenberg Jonathan E.,
von der Maase Hans,
Seigne John D.,
Mardiak Jozef,
Vaughn David J.,
Moore Malcolm,
Sahasrabudhe Deepak,
Palmer Peter A.,
PerezRuixo Juan Jose,
Small Eric J.
Publication year - 2005
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.21023
Subject(s) - medicine , chemotherapy , neutropenia , regimen , febrile neutropenia , gastroenterology , chemotherapy regimen , oncology , pharmacology , surgery
Abstract BACKGROUND R115777 is a potent farnesyl transferase inhibitor and has significant antitumor effects in vitro and in vivo. METHODS The objective of the current study was to determine the objective response proportion in patients with metastatic transitional cell carcinoma (TCC) of the urothelial tract who received treatment with R115777 at a dose of 300 mg orally given twice daily for 21 days followed by 7 days of rest for every 4‐week cycle. Thirty‐four patients with TCC were enrolled in this Phase II study. Patients were allowed to have received a maximum of one prior systemic chemotherapy regimen, not including chemoradiation or neoadjuvant chemotherapy. All patients were required to have an Eastern Cooperative Oncology Group performance status of 0–2 and adequate bone marrow, hepatic, and kidney function. RESULTS Twice daily administration of oral R115777 was tolerated well. R115777 was absorbed rapidly after oral administration. Grade 3–4 neutropenia (according to the National Cancer Institute Common Toxicity Criteria [version 2.0]) was observed in 5 patients (15%). Grade 3–4 nonhematologic toxicity was rare, consisting of rash and diarrhea in 1 patient each. Two patients (6%) without prior chemotherapy demonstrated partial responses. Thirteen patients (38%) achieved disease stabilization according to World Health Organization criteria that lasted a median of 4 months. No complete responses were observed. CONCLUSIONS The objective response rate of R115777 was not sufficient to warrant future investigation in TCC as a single agent. Preliminary evidence of the activity of R115777 in 2 chemotherapy‐naïve patients may warrant further investigation in combination with first‐line chemotherapy. Cancer 2005. © 2005 American Cancer Society.