An open-label, single-arm phase two trial of gefitinib in patients with advanced or metastatic castration-resistant prostate cancer

Am J Clin Oncol. 2009 Aug;32(4):338-41. doi: 10.1097/COC.0b013e31818b946b.

Abstract

Objective: To determine whether the oral epidermal growth factor receptor (EGFR) inhibitor gefitinib (ZD1839, Iressa has clinical efficacy in patients with castration-resistant prostate cancer (CRPC).

Methods: Multicenter open-label phase 2 study. Fifty-one male patients with CRPC and rising PSA levels were enrolled to obtain the target enrollment of 38 patients who completed at least 3 months of treatment with continuous gefitinib 500 mg/d. The primary end point was the prostate-specific antigen (PSA) response rate, as defined by a confirmed 50% decline in serum PSA.

Results: One patient had a confirmed PSA response, giving a response rate of 2.0% (95% CI 0.1-10.4%). The median time to progression was 28 days and the median time on study was 85 days. The majority of patients had a stable performance status while on study. Of the 51 patients who received at least 1 dose of gefitinib, 13 patients had a dose reduction and 9 patients withdrew because of an adverse event.

Conclusions: There was minimal evidence of single-agent gefitinib activity in CRPC. The treatment was associated with clinically relevant toxicities, which responded to dose interruption or reduction.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Agents, Hormonal / adverse effects
  • Biomarkers, Tumor / blood*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • ErbB Receptors / administration & dosage
  • ErbB Receptors / antagonists & inhibitors*
  • Gefitinib
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Orchiectomy
  • Prognosis
  • Prostate-Specific Antigen / blood*
  • Prostatic Neoplasms / blood*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / mortality
  • Quinazolines / administration & dosage*
  • Quinazolines / adverse effects
  • Risk Assessment
  • Single-Blind Method
  • Survival Analysis
  • Testosterone / blood*
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Hormonal
  • Biomarkers, Tumor
  • Quinazolines
  • Testosterone
  • ErbB Receptors
  • Prostate-Specific Antigen
  • Gefitinib