A phase II trial of the Src-kinase inhibitor saracatinib after four cycles of chemotherapy for patients with extensive stage small cell lung cancer: NCCTG trial N-0621

Lung Cancer. 2014 Aug;85(2):245-50. doi: 10.1016/j.lungcan.2014.03.004. Epub 2014 May 1.

Abstract

Introduction: To assess the efficacy and the Src-kinase inhibitor saracatinib (AZD-0530) after four cycles of platinum-based chemotherapy for extensive stage small cell lung cancer (SCLC).

Methods: Patients with at least stable disease received saracatinib at a dose of 175 mg/day by mouth until disease progression, unacceptable toxicity, or patient refusal. The primary endpoint was the 12-week progression-free survival (PFS) rate from initiation of saracatinib treatment. Planned interim analysis in first 20 patients, where 13 or more patients alive and progression-free at 12-weeks would allow continued enrollment to 40 total patients.

Results: All 23 evaluable patients received platinum based standard chemotherapy. Median age was 58 years (range: 48-82). 96% of patients had a performance status of 0/1. Median of two cycles given (range: 1-34). All 23 (100%) patients have ended treatment, most for disease progression (19/23). The 12-week PFS rate was 26% (6/23; 95% CI: 10-48%). From start of standard chemotherapy, median PFS was 4.7 months (95% CI: 4.5-5.1) and median OS was 11.2 months (95% CI: 9.9-13.8). Eight (35%) and three (13%) patients experienced at least one grade 3/4 or grade 4 AE, respectively. Commonly occurring grade 3/4 adverse events were thrombocytopenia (13%), fatigue (9%), nausea (9%), and vomiting (9%).

Conclusions: Saracatinib at a dose of 175 mg/day by mouth is well tolerated. However, the PFS rate observed at the pre-planned interim analysis did not meet the criteria for additional enrollment.

Keywords: C-Src; Extensive stage; Maintenance; Saracatinib; Small cell lung cancer.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Benzodioxoles / administration & dosage
  • Benzodioxoles / adverse effects
  • Benzodioxoles / therapeutic use*
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinazolines / administration & dosage
  • Quinazolines / adverse effects
  • Quinazolines / therapeutic use*
  • Retreatment
  • Small Cell Lung Carcinoma / drug therapy*
  • Small Cell Lung Carcinoma / mortality
  • Small Cell Lung Carcinoma / pathology*
  • Treatment Outcome
  • src-Family Kinases / antagonists & inhibitors

Substances

  • Antineoplastic Agents
  • Benzodioxoles
  • Protein Kinase Inhibitors
  • Quinazolines
  • saracatinib
  • src-Family Kinases