Lung Cancer
Volume 70, Issue 2 , Pages 180-187, November 2010

Sunitinib in combination with gemcitabine plus cisplatin for advanced non-small cell lung cancer: A phase I dose-escalation study

  • Martin Reck

      Affiliations

    • Department of Thoracic Oncology, Hospital Grosshansdorf, Grosshansdorf 22927, Germany
    • Corresponding Author InformationCorresponding author. Tel.: +49 4102 601188; fax: +49 4102 691317.
  • ,
  • Norbert Frickhofen

      Affiliations

    • Department of Oncology, HSK, Dr Horst Schmidt Klinik, Wiesbaden, Germany
  • ,
  • Susana Cedres

      Affiliations

    • Oncology Department, Vall d’Hebron University Hospital, Barcelona, Spain
  • ,
  • Ulrich Gatzemeier

      Affiliations

    • Department of Thoracic Oncology, Hospital Grosshansdorf, Grosshansdorf 22927, Germany
  • ,
  • David Heigener

      Affiliations

    • Department of Thoracic Oncology, Hospital Grosshansdorf, Grosshansdorf 22927, Germany
  • ,
  • Heinz-Georg Fuhr

      Affiliations

    • Department of Oncology, HSK, Dr Horst Schmidt Klinik, Wiesbaden, Germany
  • ,
  • Aron Thall

      Affiliations

    • Pfizer Oncology, La Jolla, CA, USA
  • ,
  • Silvana Lanzalone

      Affiliations

    • Pfizer Italia Srl, Milan, Italy
  • ,
  • Patricia Stephenson

      Affiliations

    • Rho, Inc., Chapel Hill, NC, USA
  • ,
  • Ana Ruiz-Garcia

      Affiliations

    • Pfizer Oncology, La Jolla, CA, USA
  • ,
  • Richard Chao

      Affiliations

    • Pfizer Oncology, La Jolla, CA, USA
  • ,
  • Enriqueta Felip

      Affiliations

    • Oncology Department, Vall d’Hebron University Hospital, Barcelona, Spain

Received 29 September 2009; received in revised form 21 January 2010; accepted 24 January 2010. published online 02 March 2010.

Abstract 

Purpose

To determine the maximum tolerated dose (MTD) of sunitinib plus gemcitabine/cisplatin for first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). Safety, pharmacokinetics, and antitumor activities were evaluated.

Methods

Patients ≥18 years with Eastern Cooperative Oncology Group performance status 0/1 and stage IIIB/IV NSCLC were included in this open-label, multicenter, dose-escalation phase I study. Treatment was administered in 3-week cycles: oral sunitinib 37.5 or 50mg/day intermittently (Schedule 2/1: 2 weeks on treatment, 1 week off treatment) or 25mg continuous daily dosing (CDD) schedule with intravenous infusions of gemcitabine (1000 or 1250mg/m2 days 1, 8) and cisplatin (80mg/m2 day 1).

Results

A total of 28 evaluable patients were assigned to four dose levels. Most adverse events (AEs) on the Schedule 2/1 MTD were mild to moderate. Dose delays due to myelosuppression occurred on both schedules, limiting treatment to a median of four cycles. Four of 18 evaluable patients (22%) on Schedule 2/1 and 1 of 6 patients (17%) on the CDD schedule had confirmed partial responses.

Conclusions

The MTD was identified as sunitinib 37.5mg (Schedule 2/1), gemcitabine 1250mg/m2, and cisplatin 80mg/m2, with most AEs being mild to moderate. However, frequent dose delays due to myelosuppression occurred. There was evidence of antitumor activity with this combination.

Keywords: Non-small cell lung cancer, Sunitinib, Gemcitabine, Cisplatin

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PII: S0169-5002(10)00059-0

doi:10.1016/j.lungcan.2010.01.016

Lung Cancer
Volume 70, Issue 2 , Pages 180-187, November 2010