Abstract
Purpose
To evaluate the maximum tolerated dose (MTD), safety, and antitumor activity of sunitinib combined with paclitaxel and carboplatin.
Methods
Successive cohorts of patients with advanced solid tumors received oral sunitinib (25, 37.5, or 50 mg) for 2 consecutive weeks of a 3-week cycle (Schedule 2/1) or as a continuous daily dose for 3-week cycles (CDD schedule) in combination with paclitaxel (175–200 mg/m2) plus carboplatin (AUC 6 mg min/ml) on day one of each of 4 cycles. Dose-limiting toxicities (DLTs) and adverse events (AEs) were evaluated to determine the MTD. Efficacy parameters were analyzed in patients with measurable disease.
Results
Forty-three patients were enrolled (n = 25 Schedule 2/1; n = 18 CDD schedule). Across all doses, 6 DLTs were observed [grade 4 papilledema, grade 5 GI hemorrhage, grade 3 neutropenic infection, and grade 4 thrombocytopenia (n = 3)]. The MTD for Schedule 2/1 was sunitinib 25 mg plus paclitaxel 175 mg/m2 and carboplatin AUC 6 mg min/ml. The MTD was not determined for the CDD schedule. Treatment-related AEs included neutropenia (77%), thrombocytopenia (56%), and fatigue (47%). Of 38 evaluable patients, 4 (11%) had partial responses and 12 (32%) had stable disease. PK data indicated an increase in maximum and total plasma exposures to sunitinib and its active metabolite when given with paclitaxel and carboplatin compared with sunitinib monotherapy.
Conclusions
Myelosuppression resulting in prolonged dose delays and frequent interruptions was observed, suggesting that this treatment combination is not feasible in the general cancer population.
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Acknowledgments
The authors thank all of the participating patients and their families, as well as the global network of investigators, research nurses, study coordinators, and operations staff. This study was sponsored by Pfizer Inc. Statistical support was provided by Patricia Stephenson at Rho, Inc. (Chapel Hill, NC). Medical writing support was provided by Siân Marshall at ACUMED (Tytherington, UK) and was funded by Pfizer Inc.
Conflict of interest
S. T. Kim, R. C. Chao, and A. Ruiz-Garcia are employees of Pfizer Inc. and hold stock in Pfizer Inc., the makers of SUTENT®. P. LoRusso and R. Cohen have provided consultancy/advisory support for Pfizer and received funding support from Pfizer. E. Heath has received funding support from Pfizer. G. Wilding, G. Blumenschein Jr, and N. LoConte have no potential conflicts of interest to disclose.
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Heath, E.I., Blumenschein, G.R., Cohen, R.B. et al. Sunitinib in combination with paclitaxel plus carboplatin in patients with advanced solid tumors: phase I study results. Cancer Chemother Pharmacol 68, 703–712 (2011). https://doi.org/10.1007/s00280-010-1536-1
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DOI: https://doi.org/10.1007/s00280-010-1536-1