Phase II study of the combination carboplatin plus celecoxib in heavily pre-treated recurrent ovarian cancer patients

Francesco Legge,Giovanni Scambia,Marco D'Asta,Gilda Fuoco,Amelia Paglia,Gabriella Ferrandina

doi:10.1186/1471-2407-11-214

Abstract

BackgroundCyclooxygenase-2 overexpression is associated with poor outcome and resistance to platinum-based chemotherapy in ovarian cancer. We evaluated the antitumor activity and safety of the combination carboplatin plus the COX-2 inhibitor celecoxib in recurrent heavily-treated OC patients.MethodsPatients were administered oral celecoxib (400 mg/day) in combination with intravenous carboplatin (AUC5, q28). A Simon's two-stage design was employed.Results45 patients were enrolled: 23 (51.1%) presented platinum-resistance, and 27 (60%) had received at least 3 prior regimens for recurrence. The response rate was 28.9% with 3 complete and 10 partial responses (median duration of response = 6 months). Only one (0.4%) G4 non-febrile neutropenia was observed; G3 neutropenia, anemia, or thrombocytopenia, were observed in 2.5%, 1.7%, and 1.7% of the cycles, respectively. G3-4 vomiting was reported in only 1.7%, and 0.4% of the cycles were associated with G3 dyspepsia or diarrhea or constipation. Only one patient experienced G3 hypertension associated to G2 hypersensitivity reaction. No differences in baseline versus post-treatment Quality of Life scores were observed. Median progression free survival and overall survival were 5 and 13 months, respectively.ConclusionsCelecoxib combined with carboplatin showed promising activity and it is well tolerated in heavily-treated recurrent ovarian cancer patients.Trial registration numberNCT01124435 (ClinicalTrials.gov Identifier) and 935/03 (study ID numbers).

Highlights

Cyclooxygenase-2 overexpression is associated with poor outcome and resistance to platinum-based chemotherapy in ovarian cancer
Even though it is unlikely that cardiovascular toxicity could affect the clinical outcome of poor prognosis recurrent ovarian cancer (OC) patients, these data have been considered in the selection of the celecoxib’s dose (400 mg/day) and in the eligibility criteria of the study
We have to bear in mind that in our study the experimental treatment was administered in most patients as fourth line chemotherapy, and that half of cases were characterized by primary or secondary resistance to platinating agents

Summary

Introduction

Cyclooxygenase-2 overexpression is associated with poor outcome and resistance to platinum-based chemotherapy in ovarian cancer. We evaluated the antitumor activity and safety of the combination carboplatin plus the COX-2 inhibitor celecoxib in recurrent heavily-treated OC patients. The safety of celecoxib, which, amongst COX-2 inhibitors, exhibits the greatest potency for growth inhibition [21], has been extensively studied in patients with arthritis: at doses of 400 mg/day, celecoxib presents a toxicity profile similar to traditional non-steroidal inflammatory drugs, with the advantages of a reduced incidence of gastric ulcers and symptomatic gastrointestinal adverse events [22]. Even though it is unlikely that cardiovascular toxicity could affect the clinical outcome of poor prognosis recurrent OC patients, these data have been considered in the selection of the celecoxib’s dose (400 mg/day) and in the eligibility criteria of the study

Methods

Results

Discussion

Conclusion