TY - JOUR
T1 - Sunitinib in combination with docetaxel in patients with advanced solid tumors
T2 - A phase I dose-escalation study
AU - Robert, Francisco
AU - Sandler, Alan
AU - Schiller, Joan H.
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.
PY - 2010/9
Y1 - 2010/9
N2 - 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.
AB - 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.
KW - Antiangiogenesis
KW - Docetaxel
KW - NSCLC
KW - Phase I
KW - Solid tumors
KW - Sunitinib
UR - http://www.scopus.com/inward/record.url?scp=78149356321&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78149356321&partnerID=8YFLogxK
U2 - 10.1007/s00280-009-1209-0
DO - 10.1007/s00280-009-1209-0
M3 - Article
C2 - 20043166
SN - 0343-8651
VL - 61
SP - 669
EP - 680
JO - Current Microbiology
JF - Current Microbiology
IS - 4
ER -