Cancer Chemotherapy and Pharmacology

, Volume 68, Issue 3, pp 703–712

Sunitinib in combination with paclitaxel plus carboplatin in patients with advanced solid tumors: phase I study results

  • Elisabeth I. Heath
  • George R. BlumenscheinJr
  • Roger B. Cohen
  • Patricia M. LoRusso
  • Noelle K. LoConte
  • Sindy T. Kim
  • Ana Ruiz-Garcia
  • Richard C. Chao
  • George Wilding
Original Article

DOI: 10.1007/s00280-010-1536-1

Cite this article as:
Heath, E.I., Blumenschein, G.R., Cohen, R.B. et al. Cancer Chemother Pharmacol (2011) 68: 703. doi:10.1007/s00280-010-1536-1

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.

Keywords

SunitinibPhase ISolid tumorNSCLCAntiangiogenesisChemotherapy

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Elisabeth I. Heath
    • 1
  • George R. BlumenscheinJr
    • 2
  • Roger B. Cohen
    • 3
  • Patricia M. LoRusso
    • 1
  • Noelle K. LoConte
    • 4
  • Sindy T. Kim
    • 5
  • Ana Ruiz-Garcia
    • 5
  • Richard C. Chao
    • 5
  • George Wilding
    • 4
  1. 1.Karmanos Cancer InstituteDetroitUSA
  2. 2.The University of Texas M.D. Anderson Cancer CenterHoustonUSA
  3. 3.Fox Chase Cancer CenterPhiladelphiaUSA
  4. 4.University of Wisconsin Carbone Cancer CenterMadisonUSA
  5. 5.Pfizer Oncology, Clinical DevelopmentSan DiegoUSA