A phase I study of sunitinib combined with modified FOLFOX6 in patients with advanced solid tumors
Purpose This phase I study assessed the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics, and preliminary antitumor effects of sunitinib combined with modified FOLFOX6 (mFOLFOX6). Methods Patients with advanced solid malignancies received mFOLFOX6 in 2-week cycles with escalating...
Saved in:
Published in | Cancer chemotherapy and pharmacology Vol. 70; no. 1; pp. 65 - 74 |
---|---|
Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Berlin/Heidelberg
Springer-Verlag
01.07.2012
Springer Springer Nature B.V |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Purpose
This phase I study assessed the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics, and preliminary antitumor effects of sunitinib combined with modified FOLFOX6 (mFOLFOX6).
Methods
Patients with advanced solid malignancies received mFOLFOX6 in 2-week cycles with escalating sunitinib doses (25, 37.5, and 50 mg/day) on three schedules: 2 weeks on, 2 weeks off (2/2); 4 weeks on, 2 weeks off (4/2); or continuous daily dosing (CDD). Patients received up to 8 treatment cycles (Schedule 2/2 and CDD schedule) or 6 cycles (Schedule 4/2). An expansion cohort enrolled patients with metastatic colorectal cancer at the Schedule 2/2 MTD.
Results
Overall, 53 patients were enrolled, with 43 evaluable for dose-limiting toxicity (DLT). On Schedule 2/2 (
n
= 18), DLTs occurred in three patients at 50 mg/day (grade 4 neutropenia [
n
= 1]; grades 3 and 4 thrombocytopenia [
n
= 2]) and two patients achieved partial responses (PRs). On Schedule 4/2 (
n
= 13), 37.5 mg/day exceeded the MTD with two DLTs (febrile neutropenia and grade 4 hypokalemia, respectively). On the CDD schedule (
n
= 12), the MTD was 25 mg/day; one DLT (grade 3 stomatitis) was reported and two patients achieved PRs. The most common adverse events were neutropenia, fatigue, and thrombocytopenia. No clinically significant drug–drug interactions were apparent between sunitinib, its metabolite SU12662, and mFOLFOX6.
Conclusions
Sunitinib combined with mFOLFOX6 had acceptable tolerability. The MTDs were sunitinib 50 mg/day on Schedule 2/2 and 25 mg/day on the CDD schedule. A MTD for Schedule 4/2 was not established. |
---|---|
Bibliography: | Present Address: E. Chow Maneval, Aragon Pharmaceuticals, San Diego, CA, USA |
ISSN: | 0344-5704 1432-0843 |
DOI: | 10.1007/s00280-012-1880-4 |