Phase I study of dasatinib (BMS-354825) in Japanese patients with solid tumors

Shunji Takahashi, Masaki Miyazaki, Isamu Okamoto, Yoshinori Ito, Kyoji Ueda, Taku Seriu, Kazuhiko Nakagawa, Kiyohiko Hatake

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Dasatinib is a potent oral inhibitor of tyrosine kinases including the SRC family kinases, which are activated in tumors, and implicated in invasion and bone metastasis. This phase I dose-escalation study assessed safety, tolerability, maximum tolerated dose (MTD), antitumor activity, pharmacokinetics and pharmacodynamics in Japanese patients with refractory, advanced solid tumors. Dasatinib was administered once daily at 100, 150 and 200mg/day. Sixteen patients were treated with dasatinib in the following doses: 100mg (nine patients), 150mg (three patients) and 200mg (four patients). The most frequent adverse events (AE; ≥50%) were anorexia, fatigue, pleural effusion, anemia, constipation, diarrhea, vomiting and increased aspartate aminotransferase (AST). The most frequent AE of grade ≥3 (≥10%) were anemia, decreased lymphocyte count, fatigue and increased blood magnesium. Dose-limiting toxicities were observed in two patients: grade 2 pleural effusion and bronchial wall thickening at the 100-mg level and grade 3 dyspnea at the 200-mg level. In addition, grade 2 pleural effusion was observed in all four patients treated with 200mg. Therefore, 150mg was determined to be the MTD. The pharmacokinetic parameters were comparable among the dose levels. As a pharmacodynamic study, markers of bone metabolism were assessed. Bone resorption markers, NTx and TRACP-5b, showed a decrease of 46.3% and 22.2%, respectively. No objective responses were observed, but three patients had stable disease that lasted for over 6months. In this study population, the safety profile of dasatinib was generally acceptable and 150mg of dasatinib administered once daily was determined to be the MTD.

Original languageEnglish
Pages (from-to)2058-2064
Number of pages7
JournalCancer Science
Volume102
Issue number11
DOIs
Publication statusPublished - Nov 1 2011

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Maximum Tolerated Dose
Neoplasms
Pleural Effusion
Fatigue
Anemia
Pharmacokinetics
Safety
Bone and Bones
Dasatinib
Lymphocyte Count
Anorexia
Constipation
Bone Resorption
Aspartate Aminotransferases
Dyspnea
Protein-Tyrosine Kinases
Magnesium
Vomiting
Diarrhea
Phosphotransferases

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Takahashi, S., Miyazaki, M., Okamoto, I., Ito, Y., Ueda, K., Seriu, T., ... Hatake, K. (2011). Phase I study of dasatinib (BMS-354825) in Japanese patients with solid tumors. Cancer Science, 102(11), 2058-2064. https://doi.org/10.1111/j.1349-7006.2011.02041.x

Phase I study of dasatinib (BMS-354825) in Japanese patients with solid tumors. / Takahashi, Shunji; Miyazaki, Masaki; Okamoto, Isamu; Ito, Yoshinori; Ueda, Kyoji; Seriu, Taku; Nakagawa, Kazuhiko; Hatake, Kiyohiko.

In: Cancer Science, Vol. 102, No. 11, 01.11.2011, p. 2058-2064.

Research output: Contribution to journalArticle

Takahashi, S, Miyazaki, M, Okamoto, I, Ito, Y, Ueda, K, Seriu, T, Nakagawa, K & Hatake, K 2011, 'Phase I study of dasatinib (BMS-354825) in Japanese patients with solid tumors', Cancer Science, vol. 102, no. 11, pp. 2058-2064. https://doi.org/10.1111/j.1349-7006.2011.02041.x
Takahashi, Shunji ; Miyazaki, Masaki ; Okamoto, Isamu ; Ito, Yoshinori ; Ueda, Kyoji ; Seriu, Taku ; Nakagawa, Kazuhiko ; Hatake, Kiyohiko. / Phase I study of dasatinib (BMS-354825) in Japanese patients with solid tumors. In: Cancer Science. 2011 ; Vol. 102, No. 11. pp. 2058-2064.
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