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)

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-fine 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 >= 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. (C) 2009 Elsevier Inc. All rights reserved.