A phase I study of sunitinib combined with modified FOLFOX6 in patients with advanced solid tumors

S. Leong, S. G. Eckhardt, E. Chan, W. A. Messersmith, J. Spratlin, D. R. Camidge, S. Diab, R. Khosravan, X. Lin, E. Chow Maneval, A. C. Lockhart

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)65-74
Number of pages10
JournalCancer Chemotherapy And Pharmacology
Volume70
Issue number1
DOIs
StatePublished - Jul 2012
Externally publishedYes

Keywords

  • FOLFOX
  • Pharmacokinetics
  • Phase I
  • Solid tumors
  • Sunitinib
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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