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

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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

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docetaxel
Appointments and Schedules
Maximum Tolerated Dose
Neoplasms
Pharmacokinetics
Drug Interactions
sunitinib
Safety

Keywords

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

ASJC Scopus subject areas

  • Microbiology
  • Applied Microbiology and Biotechnology

Cite this

Robert, F., Sandler, A., Schiller, J. H., Liu, G., Harper, K., Verkh, L., ... 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

Sunitinib in combination with docetaxel in patients with advanced solid tumors : A phase I dose-escalation study. / Robert, Francisco; Sandler, Alan; Schiller, Joan H.; Liu, Glenn; Harper, Karen; Verkh, Lev; Huang, Xin; Ilagan, Jennifer; Tye, Lesley; Chao, Richard; Traynor, Anne M.

In: Current Microbiology, Vol. 61, No. 4, 09.2010, p. 669-680.

Research output: Contribution to journalArticle

Robert, F, Sandler, A, Schiller, JH, Liu, G, Harper, K, Verkh, L, Huang, X, Ilagan, J, Tye, L, Chao, R & Traynor, AM 2010, 'Sunitinib in combination with docetaxel in patients with advanced solid tumors: A phase I dose-escalation study', Current Microbiology, vol. 61, no. 4, pp. 669-680. https://doi.org/10.1007/s00280-009-1209-0
Robert, Francisco ; Sandler, Alan ; Schiller, Joan H. ; Liu, Glenn ; Harper, Karen ; Verkh, Lev ; Huang, Xin ; Ilagan, Jennifer ; Tye, Lesley ; Chao, Richard ; Traynor, Anne M. / Sunitinib in combination with docetaxel in patients with advanced solid tumors : A phase I dose-escalation study. In: Current Microbiology. 2010 ; Vol. 61, No. 4. pp. 669-680.
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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.",
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AU - Liu, Glenn

AU - Harper, Karen

AU - Verkh, Lev

AU - Huang, Xin

AU - Ilagan, Jennifer

AU - Tye, Lesley

AU - Chao, Richard

AU - Traynor, Anne M.

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