Document Type
Article
Department
Haematology and Oncology, East Africa
Abstract
Purpose: Bosutinib, a potent ATP-competitive, quinolinecarbonitrile Src/Abl kinase inhibitor, was tested in this first-in-human phase I trial in patients with advanced solid tumor malignancies.
Patients and Methods: This trial was conducted in 2 parts. In part 1 (dose escalation), increasing oral bosutinib doses were administered using a 3 + 3 design. In part 2 (dose expansion), approximately 30 patients each with refractory colorectal, pancreas, or non–small cell lung cancer were treated at the recommended phase II dose (RP2D). Primary efficacy endpoints for part 2 were median progression-free survival (colorectal and non–small cell lung) and median overall survival (pancreas).
Results: In part 1, dose-limiting toxicities of grade 3 diarrhea (two patients) and grade 3 rash occurred with bosutinib 600 mg/day and the maximum tolerated dose identified was 500 mg/day. However, the majority of patients treated with 500 mg/day had grade 2 or greater gastrointestinal toxicity, and 400 mg/day was identified as the RP2D. The most common bosutinib-related adverse events were nausea (60% patients), diarrhea (47%), vomiting (40%), fatigue (38%), and anorexia (36%). Bosutinib had a mean half-life of 19 to 20 hours at the RP2D. A partial response (breast) and unconfirmed complete response (pancreas) were observed; 8 of 112 evaluable patients had stable disease for 22 to 101 weeks. However, the primary efficacy endpoints for part 2 were not met.
Conclusions: Bosutinib was generally well tolerated in patients with solid tumors, with the main toxicity being gastrointestinal. The RP2D was 400 mg/day orally. Further study of bosutinib is planned in combination regimens.
Publication (Name of Journal)
Cancer Clinical Research
DOI
https://doi.org/10.1158/1078-0432.CCR-11-2378
Recommended Citation
Daud, A.,
Krishnamurthi, S.,
Saleh, M.,
Gitlitz, B.,
Borad, M.,
Gold, P.,
Chiorean, E.,
Springett, G.,
Abbas, R.,
Agarwal, S.
(2012). Phase I study of bosutinib, a src/Abl tyrosine kinase inhibitor, administered to patients with advanced solid tumors. Cancer Clinical Research, 18(4), 1-9.
Available at:
https://ecommons.aku.edu/eastafrica_fhs_mc_haematol_oncol/85
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Comments
This work was published before the author joined Aga Khan University.