Nonpegylated Liposomal Doxorubicin (TLC-D99), Paclitaxel, and Trastuzumab in HER-2-Overexpressing Breast Cancer: A Multicenter Phase I/II Study
Por:
Cortes, J, DiCosimo, S, Climent, MA, Cortes-Funes, H, Lluch, A, Gascon, P, Mayordomo, JI, Gil, M, Benavides, M, Cirera, L, Ojeda, B, Rodriguez, CA, Trigo, JM, Vazquez, J, Regueiro, P, Dorado, JF, Baselga, J
Publicada:
1 ene 2009
Resumen:
Purpose: To determine the recommended dose, cardiac safety, and antitumor activity of nonpegylated liposomal doxorubicin (TLC-D99), paclitaxel, and the anti-HER-2 monoclonal antibody trastuzumab in patients with HER-2-overexpressing locally advanced nonoperable breast cancer (LABC) and metastatic breast cancer (MBC).
Experimental Design: Women with measurable, previously untreated, HER-2-overexpressing LABC and MBC with a baseline left ventricular ejection fraction (LVEF) > 50% received weekly trastuzumab in combination with escalating doses of weekly paclitaxel and TLC-D99 every 3 weeks for 6 cycles. LVEF monitoring was done every 3 weeks for the first 18 weeks and every 8 weeks thereafter.
Results: Sixty-nine patients participated, 15 in the dose escalating part and 54 at the recommended phase 11 dose (28 patients with LABC and 26 patients with MBC).The recommended doses of TLC-D99 and paclitaxel were 50 mg/m(2) every 3 weeks and 80 mg/m(2)/wk, respectively. Twelve (17%) patients developed asymptomatic declines in LVEF. In 8 of these patients, LVEF recovered to >= 50% after a median time of 9 weeks (range, 3-38 weeks). In the rest of patients, LVEF ranged from 44% to 49%. No patients developed symptomatic cardiac heart failure.The overall response rate was 98.1% (95% confidence interval, 90.1-99.9) with a median time to progression not reached in LABC and of 22.1 months (95% confidence interval, 16.4-46.3) in MBC patients.
Conclusions: Nonpegylated doxorubicin, paclitaxel, and trastuzumab combination is safe, does not result in clinically manifest cardiac toxicity, and has a high rate of durable responses in HER-2-overexpressing breast cancer patients. Further exploration of this combination is warranted.
Filiaciones:
Cortes, J:
Vall Hebron Univ Hosp, Dept Med Oncol, Barcelona 08035, Spain
DiCosimo, S:
Vall Hebron Univ Hosp, Dept Med Oncol, Barcelona 08035, Spain
Climent, MA:
Instituto Valenciano de Oncología, Valencia, Spain
Cortes-Funes, H:
Hosp Univ 12 Octubre, Madrid, Spain
Lluch, A:
Hosp Clin Univ, Valencia, Spain
Gascon, P:
Hosp Clin Barcelona, Barcelona, Spain
Mayordomo, JI:
Hosp Clin Univ Zaragoza, Zaragoza, Spain
Gil, M:
Hosp Llobregat, Inst Catala Oncol, Barcelona, Spain
Benavides, M:
Hosp Carlos Haya, Malaga, Spain
Cirera, L:
Hosp Mutua Terrasa, Terrassa, Spain
Ojeda, B:
Hospital Santa Creu i Sant Pau, SOLTI, Barcelona, Spain
Rodriguez, CA:
Hosp Clin Salamanca, Salamanca, Spain
Trigo, JM:
Vall Hebron Univ Hosp, Dept Med Oncol, Barcelona 08035, Spain
Vazquez, J:
SOLTI, Spanish Breast Canc Cooperat Grp Operat Off, Barcelona, Spain
Regueiro, P:
Roche Farma SA, Madrid, Spain
Dorado, JF:
SGS Life Sci Serv, Madrid, Spain
Baselga, J:
Vall Hebron Univ Hosp, Dept Med Oncol, Barcelona 08035, Spain
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