Phase II study of gefitinib in combination with paclitaxel (P) and carboplatin (C) as second-line therapy for ovarian, tubal or peritoneal adenocarcinoma (1839IL/0074)

Gynecol Oncol. 2010 Feb;116(2):157-62. doi: 10.1016/j.ygyno.2009.10.076.

Abstract

Objective: This phase II investigated efficacy and tolerability of gefitinib in combination with paclitaxel (P) and carboplatin (C) for second-line treatment of patients (pts) with ovarian, tubal or peritoneal adenocarcinoma.

Patients and methods: Women (>18 years) with platinum-resistant/refractory (relapsed<6 months), or platinum-sensitive (relapsed >6 months) disease after first-line platinum-based and P chemotherapy. Pts received 6-8 cycles of gefitinib (500 mg/day), P (175 mg/m(2) 3 h infusion) and C (AUC 5) every 3 weeks, followed by gefitinib alone. The primary endpoint was objective response rate (ORR) (RECIST or Rustin criteria).

Results: Sixty-eight patients (26 resistant/refractory and 42 sensitive) were enrolled (median age: 57 years). ORR and disease control rates were 19.2% and 69.2% for resistant/refractory, and 61.9% and 81.0%, for sensitive disease. Median time to progression and overall median survivals were 6.1 and 16.9 months for resistant/refractory and 9.2 and 25.7 months for sensitive disease. Grade 3/4 toxicities (in > or = 10% patients) were neutropenia (59%), diarrhea (25%), leukopenia (22%), anemia (13%), and acne (13%). Two secondary myelodysplastic syndromes (MDS) and one secondary acute leukemia occurred during treatment, and one MDS 34 months after treatment discontinuation.

Conclusion: Gefitinib, administered in combination with paclitaxel and carboplatin, provides a good clinical response but associated with an increased risk of hematologic disorders.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Carboplatin / adverse effects
  • Disease-Free Survival
  • Fallopian Tube Neoplasms / drug therapy*
  • Female
  • Gefitinib
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / drug therapy*
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects
  • Peritoneal Neoplasms / drug therapy*
  • Quinazolines / administration & dosage
  • Quinazolines / adverse effects

Substances

  • Quinazolines
  • Carboplatin
  • Paclitaxel
  • Gefitinib