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Titolo:
Phase I and pharmacologic study of sequences of gemcitabine and the multitargeted antifolate agent in patients with advanced solid tumors
Autore:
Adjei, AA; Erlichman, C; Sloan, JA; Reid, JM; Pitot, HC; Goldberg, RM; Peethambaram, P; Atherton, P; Hanson, LJ; Alberts, SR; Jett, J;
Indirizzi:
Mayo Clin & Mayo Fdn, Div Med Oncol, Dept Oncol, Rochester, MN 55905 USA Mayo Clin & Mayo Fdn Rochester MN USA 55905 ncol, Rochester, MN 55905 USA
Titolo Testata:
JOURNAL OF CLINICAL ONCOLOGY
fascicolo: 8, volume: 18, anno: 2000,
pagine: 1748 - 1757
SICI:
0732-183X(200004)18:8<1748:PIAPSO>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
21
Recensione:
Indirizzi per estratti:
Indirizzo: Adjei, AA Mayo Clin & Mayo Fdn, Div Med Oncol, Dept Oncol, 200 1st St SW, Rochester,MN 55905 USA Mayo Clin & Mayo Fdn 200 1st St SW Rochester MN USA 55905 05 USA
Citazione:
A.A. Adjei et al., "Phase I and pharmacologic study of sequences of gemcitabine and the multitargeted antifolate agent in patients with advanced solid tumors", J CL ONCOL, 18(8), 2000, pp. 1748-1757

Abstract

Purpose: Multitargeted antifolate (MTA) is an investigational agent that, like gemcitabine, exhibits broad activity in solid tumors. A phase I trial of MTA and gemcitabine was undertaken, based on the demonstration of preclinical cytotoxic synergy. Patients and Methods: Thirty-five patients (group I) received 164 courses (median, four; range, one to 14 courses) of treatment of gemcitabine at doses of 1,000 and 1,250 mg/m(2) on days 1 and 8 and MTA at doses of 200, 300,400, 500, and 680 mg/m(2), given 90 minutes after gemcitabine on day 1. Courses were repeated every 3 weeks. Because the day 8 dose of gemcitabine wets reduced or omitted in 57% of courses due to neutropenia, 21 patients (group II) were treated on an alternate schedule, with MTA administered on day8 rather than day 1. This group received 85 treatment courses (median, four; range, one to 10 courses). Results: The most common and dose-limiting toxicity was neutropenia. Othertoxicities included nausea, fatigue, rash, and elevated hepatic transaminases. The maximum-tolerated dose was gemcitabine/MTA 1,000/500 mg/m(2) for group I and 1,250/500 mg/m2 for group II. Thirteen objective responses were documented (colorectal cancer, n = 3; non-small-cell lung cancer, n = 3; cholangiocarcinoma, n = 2; ovarian carcinoma, n = 2; mesothelioma, n = 1; breast cancer, n = 1; and adenocarcinoma of unknown primary site, n = 1). Gemcitabine had no effect on the disposition of MTA. Conclusion: The gemcitabine/MTA combination is broadly active and warrantsfurther evaluation. The sequence of gemcitabine administered on days 1 and8 with MTA administered on day 8 is better tolerated and is recommended for further study at doses of gemcitabine/MTA 1,250/500 mg/m(2). J Clin Oncol 18:1748-1757. (C) 2000 by American Society of Clinical Oncology.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 15/07/20 alle ore 06:29:36