Combination of Docetaxel Plus Savolitinib in Refractory Cancer Patients: A Report on Phase I Trialopen access
- Authors
- Kim, S.T.[Kim, S.T.]; Lee, S.[Lee, S.]; Park, M.[Park, M.]; Park, S.H.[Park, S.H.]; Park, J.O.[Park, J.O.]; Lim, H.Y.[Lim, H.Y.]; Park, Y.S.[Park, Y.S.]; Kang, W.K.[Kang, W.K.]; Gangolli, E.A.[Gangolli, E.A.]; Shin, H.[Shin, H.]; Kim, K.-M.[Kim, K.-M.]; Hollingsworth, S.J.[Hollingsworth, S.J.]; Mortimer, P.G.S.[Mortimer, P.G.S.]; Lee, J.[Lee, J.]
- Issue Date
- Apr-2019
- Publisher
- Neoplasia Press, Inc.
- Citation
- Translational Oncology, v.12, no.4, pp.597 - 601
- Indexed
- SCIE
SCOPUS
- Journal Title
- Translational Oncology
- Volume
- 12
- Number
- 4
- Start Page
- 597
- End Page
- 601
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/15886
- DOI
- 10.1016/j.tranon.2018.12.009
- ISSN
- 1936-5233
- Abstract
- MET amplification is a frequently observed genomic aberration in solid tumors. We conducted a phase I trial to evaluate dose-limiting toxicity (DLT) and recommended phase II dose (RP2D) for the combination therapy. The following dose levels were tested in this single-arm phase I study: docetaxel as an intravenous infusion over 1 hour at 60 mg/m2 once every 3 weeks of a 21-day schedule plus savolitinib (level 1, 200 mg qd; level 2, 400 mg qd; level 3, 600 mg qd; level 4800 mg qd). In total, there were 17 patients enrolled on to this study [7 gastric cancer (GC) patients, 5 melanoma patients, 3 sarcoma patients, and 2 rectal cancer patients]. Most of the patients (14 of 17) were heavily pretreated (≥third line or greater lines of treatment). For the first 3 cohorts (200 mg savolitinib + docetaxel 60 mg/m2, 400 mg savolitinib + docetaxel 60 mg/m2, 600 mg savolitinib + docetaxel 60 mg/m2), there were no DLTs. In the fourth dose cohort (800 mg savolitinib + docetaxel 60 mg/m2), one DLT occurred with generalized edema grade 3 that required intensive management. One GC patient with both MET overexpression (3+) and MET amplification (MET/CEP7 ratio, 7.3) achieved a durable partial response for 297 days, and another MET-amplified GC patient (MET/CEP7 ratio, 7.6) achieved stable disease for 86 days. Due to the higher incidence of G4 neutropenia in cohort 4 (800 mg), we recommend savolitinib 600 mg qd in combination with docetaxel 60 mg/m2 as the RP2D for phase II trial. The combination therapy demonstrated a very promising antitumor activity with durable responses in MET amplified GC patients. © 2019 The Authors
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - Medicine > Department of Medicine > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/15886)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.