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A randomized phase II feasibility trial of BMS-275291 in patients with early stage breast cancer.
Miller, Kathy D; Saphner, Thomas J; Waterhouse, David M; Chen, T-T; Rush-Taylor, Anita; Sparano, Joseph A; Wolff, Antonio C; Cobleigh, Melody A; Galbraith, Susan; Sledge, George W.
Afiliação
  • Miller KD; Indiana University, Indianapolis, Indiana, USA. kathmill@iupui.edu
Clin Cancer Res ; 10(6): 1971-5, 2004 Mar 15.
Article em En | MEDLINE | ID: mdl-15041714
ABSTRACT

PURPOSE:

This pilot trial was performed to evaluate the safety, pharmacokinetics and feasibility of incorporating BMS-275291, a matrix metalloproteinase inhibitor (MMPI), into adjuvant breast cancer therapy. EXPERIMENTAL

DESIGN:

Patients with stage I (T1c)-IIIA breast cancer were eligible if planned adjuvant therapy consisted of either tamoxifen alone, doxorubicin + cyclophosphamide every 21 days for four cycles (AC), or AC followed by paclitaxel every 21 days for 4 cycles (AC>T). Patients were stratified by planned adjuvant therapy and randomized (21 ratio) to BMS-275291 (1200 mg/day) or matched placebo for 1 year.

RESULTS:

Seventy-two patients were recruited from March 2001 to July 2002. Grade >or=2 musculoskeletal toxicity, generally reversible arthralgia, was reported by 36.2% of patients receiving BMS-275291 compared with 16.7% of patients receiving placebo; difference = 19.5% (95% confidence interval -0.06, 0.44; P = NS). Two patients receiving BMS-275291 developed palpable nodules along tendons. Grade >or=3 rash was reported by 8.5% of patients receiving BMS-275291 compared with 4.2% of patients receiving placebo; difference = 4.3% (95% confidence interval -0.18, 0.3; P = NS). Overall, 33% of BMS-275291 patients and 21% of placebo patients discontinued treatment due to adverse events. BMS-275291 trough levels tended to decrease over time; 9 of 47 (19%) had >or=50% of trough concentrations > 124 ng/ml (IC(90) for matrix metalloproteinase-9).

CONCLUSIONS:

The pattern of arthralgia in BMS-275291-treated patients was consistent with matrix metalloproteinase inhibitor toxicity. Although the differential incidence of arthralgia did not reach statistical significance, the trial was terminated. An adjuvant trial in this patient population is not feasible.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Compostos Orgânicos / Neoplasias da Mama / Inibidores de Metaloproteinases de Matriz / Antineoplásicos Tipo de estudo: Clinical_trials Limite: Aged / Female / Humans / Middle aged Idioma: En Ano de publicação: 2004 Tipo de documento: Article
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Compostos Orgânicos / Neoplasias da Mama / Inibidores de Metaloproteinases de Matriz / Antineoplásicos Tipo de estudo: Clinical_trials Limite: Aged / Female / Humans / Middle aged Idioma: En Ano de publicação: 2004 Tipo de documento: Article