TY - JOUR
T1 - A phase 1, dose-finding and pharmacokinetic study of gemcitabine with nab-paclitaxel in patients with metastatic breast cancer
AU - Yoshitomi, Seiji
AU - Taira, Naruto
AU - Doihara, Hiroyoshi
AU - Mizoo, Taeko
AU - Nogami, Tomohiro
AU - Iwamoto, Takayuki
AU - Motoki, Takayuki
AU - Shien, Tadahiko
AU - Ogasawara, Yutaka
AU - Matsuoka, Junji
AU - Tsuji, Hisashi
AU - Mitsuhashi, Toshiharu
PY - 2016/8/1
Y1 - 2016/8/1
N2 - Purpose: Gemcitabine (Gem) with paclitaxel (Pac) is used for patients with metastatic breast cancer who require cytoreduction with manageable toxicities. Nanoparticle albumin-bound (nab)-Pac exhibits better efficacy and reduces the risk of hypersensitivity reactions associated with solvent-based Pac. Therefore, Gem plus nab-Pac (GA) therapy may be effective for metastatic breast cancer. The purpose of this study was to determine the maximum tolerated dose for GA therapy. Methods: The subjects were patients with metastatic breast cancer with performance status 0 or 1 and normal hepatic, renal and marrow function. Leukopenia, neutropenia or thrombocytopenia of grade 4, neutropenic fever, or non-hematological toxicity of grade 3 or higher during the 1st cycle, and chemotherapy-induced peripheral neurotoxicity of grade 2 or higher at the end of the 1st cycle were defined as dose-limiting toxicities (DLTs). Gem (1250 mg/m2) was administered on days 1 and 8. nab-Pac was administered at a starting dose of 180 mg/m2(cohort 1) and escalated to 220 mg/m2(cohort 2) and 260 mg/m2(cohort 3) on day 1 of the 21-day cycle, using a 3 + 3 design. Results: Nine patients (n = 3, 3, and 3 in cohorts 1, 2, and 3, respectively) were included in the study (median age 56 years; range 43–75 years). DLTs did not occur in any cohorts. Conclusions: The initial recommend dose in GA therapy is 1250 mg/m2Gem and 260 mg/m2nab-Pac. It is well known that nab-Pac has cumulative toxicities, and thus the efficacy and safety of GA therapy require validation in a phase 2 study.
AB - Purpose: Gemcitabine (Gem) with paclitaxel (Pac) is used for patients with metastatic breast cancer who require cytoreduction with manageable toxicities. Nanoparticle albumin-bound (nab)-Pac exhibits better efficacy and reduces the risk of hypersensitivity reactions associated with solvent-based Pac. Therefore, Gem plus nab-Pac (GA) therapy may be effective for metastatic breast cancer. The purpose of this study was to determine the maximum tolerated dose for GA therapy. Methods: The subjects were patients with metastatic breast cancer with performance status 0 or 1 and normal hepatic, renal and marrow function. Leukopenia, neutropenia or thrombocytopenia of grade 4, neutropenic fever, or non-hematological toxicity of grade 3 or higher during the 1st cycle, and chemotherapy-induced peripheral neurotoxicity of grade 2 or higher at the end of the 1st cycle were defined as dose-limiting toxicities (DLTs). Gem (1250 mg/m2) was administered on days 1 and 8. nab-Pac was administered at a starting dose of 180 mg/m2(cohort 1) and escalated to 220 mg/m2(cohort 2) and 260 mg/m2(cohort 3) on day 1 of the 21-day cycle, using a 3 + 3 design. Results: Nine patients (n = 3, 3, and 3 in cohorts 1, 2, and 3, respectively) were included in the study (median age 56 years; range 43–75 years). DLTs did not occur in any cohorts. Conclusions: The initial recommend dose in GA therapy is 1250 mg/m2Gem and 260 mg/m2nab-Pac. It is well known that nab-Pac has cumulative toxicities, and thus the efficacy and safety of GA therapy require validation in a phase 2 study.
KW - Chemotherapy-induced peripheral neurotoxicity
KW - Gemcitabine
KW - Metastatic breast cancer
KW - Nanoparticle albumin-bound paclitaxel
KW - Phase 1
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U2 - 10.1007/s00280-016-3091-x
DO - 10.1007/s00280-016-3091-x
M3 - Article
C2 - 27316438
AN - SCOPUS:84975122056
VL - 78
SP - 289
EP - 294
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
SN - 0344-5704
IS - 2
ER -