A phase 1, dose-finding and pharmacokinetic study of gemcitabine with nab-paclitaxel in patients with metastatic breast cancer.
OBJECTIVE
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/m(2)) was administered on days 1 and 8. nab-Pac was administered at a starting dose of 180 mg/m(2) (cohort 1) and escalated to 220 mg/m(2) (cohort 2) and 260 mg/m(2) (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/m(2) Gem and 260 mg/m(2) nab-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.
Department of Breast and Endocrine Surgery, Red Cross Okayama Hospital, 2-1-1 Aoe, Okayama, Okayama, 700-8607, Japan.
Seiji
S
Yoshitomi
Department of Breast and Endocrine Surgery, Okayama University Hospital, 2-5-1 Shikata-cho, Okayama, Okayama, 700-8558, Japan. ntaira@md.okayama-u.ac.jp.
Naruto
N
Taira
Department of Breast and Endocrine Surgery, Okayama University Hospital, 2-5-1 Shikata-cho, Okayama, Okayama, 700-8558, Japan.
Hiroyoshi
H
Doihara
Department of Breast and Endocrine Surgery, Okayama University Hospital, 2-5-1 Shikata-cho, Okayama, Okayama, 700-8558, Japan.
Taeko
T
Mizoo
Department of Breast and Endocrine Surgery, Okayama University Hospital, 2-5-1 Shikata-cho, Okayama, Okayama, 700-8558, Japan.
Tomohiro
T
Nogami
Department of Breast and Endocrine Surgery, Okayama University Hospital, 2-5-1 Shikata-cho, Okayama, Okayama, 700-8558, Japan.
Takayuki
T
Iwamoto
Department of Breast and Endocrine Surgery, Okayama University Hospital, 2-5-1 Shikata-cho, Okayama, Okayama, 700-8558, Japan.
Takayuki
T
Motoki
Department of Breast and Endocrine Surgery, Okayama University Hospital, 2-5-1 Shikata-cho, Okayama, Okayama, 700-8558, Japan.
Tadahiko
T
Shien
Department of Breast and Endocrine Surgery, Kagawa Prefectural Central Hospital, 1-2-1 Asahi-machi, Takamatsu, Kagawa, 760-8557, Japan.
Yutaka
Y
Ogasawara
Department of Breast and Endocrine Surgery, Okayama University Hospital, 2-5-1 Shikata-cho, Okayama, Okayama, 700-8558, Japan.
Junji
J
Matsuoka
Department of Breast and Endocrine Surgery, Red Cross Okayama Hospital, 2-1-1 Aoe, Okayama, Okayama, 700-8607, Japan.
Hisashi
H
Tsuji
Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Okayama, Okayama, 700-8558, Japan.
Toshiharu
T
Mitsuhashi
D000328:Adult; D000368:Aged; D000418:Albumins / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage; D000093542:Gemcitabine
C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D003841:Deoxycytidine; D017239:Paclitaxel; D000093542:Gemcitabine
Chemotherapy-induced peripheral neurotoxicity; Gemcitabine; Metastatic breast cancer; Nanoparticle albumin-bound paclitaxel; Phase 1