Sunitinib in combination with docetaxel in patients with advanced solid tumors: A phase I dose-escalation study

Francisco Robert, Alan Sandler, Joan H. Schiller, Glenn Liu, Karen Harper, Lev Verkh, Xin Huang, Jennifer Ilagan, Lesley Tye, Richard Chao, Anne M. Traynor

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Purpose: Sunitinib in combination with docetaxel enhances antitumor activity in xenograft models of human breast and non-small cell lung cancer. We assessed the maximum tolerated doses (MTDs), safety, pharmacokinetic profiles, and preliminary efficacy of sunitinib plus docetaxel in patients with advanced solid tumors. Methods: In this phase I study, successive patient cohorts received sunitinib 25, 37.5, or 50 mg/day for 4 weeks of a 6-week cycle (Schedule 4/2, 4 weeks on, 2 weeks off) or for 2 weeks of a 3-week cycle (Schedule 2/1, 2 weeks on, 1 week off) with docetaxel 60 or 75 mg/m2 IV q21d to determine the MTDs of this treatment combination. Results Fifty patients enrolled: 10 on Schedule 4/2 and 40 on Schedule 2/1. MTDs were established as sunitinib 25 mg on Schedule 4/2 with docetaxel 60 mg/m 2 q21d, and as sunitinib 37.5 mg on Schedule 2/1 with docetaxel 75 mg/m2 q21d. On Schedule 2/1, the most frequent doselimiting toxicity was neutropenia (±fever; grade [G]3/4, n = 5) and the most common G3/4 non-hematologic adverse event (AE) was fatigue (G3, n = 8). Hematologic AEs were managed with growth factor support in 11 of 23 (48%) patients treated at Schedule 2/1 MTD. Three patients achieved a partial response at the Schedule 2/1 MTD. There were no pharmacokinetic drug-drug interactions with either schedule. Conclusions Oral sunitinib 37.5 mg/day on Schedule 2/1 with docetaxel 75 mg/m2 IV q21d is a clinically feasible regimen with a manageable safety profile, no pharmacokinetic drug-drug interactions, and shows antitumor activity in patients with advanced solid tumors.

Original languageEnglish (US)
Pages (from-to)669-680
Number of pages12
JournalCurrent Microbiology
Volume61
Issue number4
DOIs
StatePublished - Sep 2010

Keywords

  • Antiangiogenesis
  • Docetaxel
  • NSCLC
  • Phase I
  • Solid tumors
  • Sunitinib

ASJC Scopus subject areas

  • Microbiology
  • Applied Microbiology and Biotechnology

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    Robert, F., Sandler, A., Schiller, J. H., Liu, G., Harper, K., Verkh, L., Huang, X., Ilagan, J., Tye, L., Chao, R., & Traynor, A. M. (2010). Sunitinib in combination with docetaxel in patients with advanced solid tumors: A phase I dose-escalation study. Current Microbiology, 61(4), 669-680. https://doi.org/10.1007/s00280-009-1209-0