論文

査読有り
2015年10月

Phase I trial of afatinib plus vinorelbine in Japanese patients with advanced solid tumors, including breast cancer

CANCER CHEMOTHERAPY AND PHARMACOLOGY
  • Hirofumi Mukai
  • Norikazu Masuda
  • Hiroshi Ishiguro
  • Ayako Mitsuma
  • Takashi Shibata
  • Jun Yamamura
  • Masakazu Toi
  • Aiko Watabe
  • Akiko Sarashina
  • Martina Uttenreuther-Fischer
  • Yuichi Ando
  • 全て表示

76
4
開始ページ
739
終了ページ
750
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1007/s00280-015-2826-4
出版者・発行元
SPRINGER

This phase I trial assessed afatinib, an irreversible ErbB family blocker, plus vinorelbine in Japanese patients with advanced solid tumors not amenable to standard treatment.
Primary objectives were evaluation of safety and the maximum tolerated dose (MTD) of once-daily (QD) afatinib plus weekly intravenous vinorelbine. Secondary objectives included pharmacokinetic assessments and preliminary efficacy. Dose finding utilized a 3 + 3 design, with a starting dose of afatinib 20 mg QD plus vinorelbine 25 mg/m(2) weekly.
Seventeen patients were enrolled. Dose level 2 (afatinib 40 mg and vinorelbine 25 mg/m(2)) exceeded the MTD; dose-limiting toxicities (DLTs) were considered vinorelbine-related. Dose finding continued with modified dose levels; dose level 2a: afatinib 40 mg and a reduced dose of vinorelbine 20 mg/m(2) and dose level 3: afatinib 40 mg and vinorelbine 25 mg/m(2) allowing omission of vinorelbine for grade a parts per thousand yen2 neutropenia/thrombocytopenia and afatinib dose modification for adverse events (AEs). At dose level 3, 1/6 patients had a DLT (upper abdominal pain requiring afatinib dose reduction). Overall, the most frequent treatment-related AEs (any/grade 3 and 4) were: neutropenia (100/71 %), leukopenia (100/59 %), diarrhea (94/0 %), anemia (71/12 %) and stomatitis (65/0 %). Two patients with breast cancer achieved a partial response; eight patients (various cancer indications) had stable disease. Pharmacokinetic analyses suggested no relevant drug-drug interactions.
Afatinib 40 mg QD plus vinorelbine 25 mg/m(2) weekly was tolerated in Japanese patients when dose modifications for known AEs for either compound were allowed. Tumor shrinkage was also observed. This dose schedule was recommended for phase II/III trials in Japanese patients.

リンク情報
DOI
https://doi.org/10.1007/s00280-015-2826-4
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000361494600008&DestApp=WOS_CPL
ID情報
  • DOI : 10.1007/s00280-015-2826-4
  • ISSN : 0344-5704
  • eISSN : 1432-0843
  • Web of Science ID : WOS:000361494600008

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