Objective To assess the efficacy of dose-dense weekly paclitaxel plus carboplatin in metastatic or recurrent cervical carcinoma, we conducted a phase II/III randomized controlled study comparing dose-dense paclitaxel and carboplatin with or without bevacizumab to conventional paclitaxel and carboplatin with or without bevacizumab. However, at the primary analysis of the phase II part, the response rate in the dose-dense arm was not higher than in the conventional arm and the study was terminated early before starting phase III. After a further 2 years of follow-up, we conducted this final analysis.
Methods 122 patients were enrolled and randomly assigned to either the conventional or dose-dense arm. After bevacizumab was approved in Japan, patients in both arms received bevacizumab if not contraindicated. In the final analysis, overall survival, progression-free survival, and adverse events were updated.
Results The median follow-up of surviving patients was 34.8 months (range 19.2–64.8). Median overall survival in the conventional arm was 17.7 months and in the dose-dense arm 18.5 months (p=0.71). Median progression-free survival in the conventional arm was 7.9 months and in the dose-dense arm 7.2 months (p=0.64). A platinum-free interval within 24 weeks and treatment without bevacizumab were identified as prognostic factors for overall and progression-free survival. Grade 3 to 4 non-hematologic toxicity occurred in 46.7% of patients who received the conventional regimen and in 43.3% of patients who received the dose-dense regimen. Adverse events related to bevacizumab in 82 patients included fistula in five (6.1%) and gastrointestinal perforation in three (3.7%).
Conclusions It was confirmed that dose-dense paclitaxel plus carboplatin for metastatic or recurrent cervical carcinoma is not superior to conventional paclitaxel and carboplatin. Patients who had early refractory disease after prior chemoradiotherapy had the poorest prognosis. The development of treatments that improve the prognosis of such patients remains an important issue.
Clinical trial information: jRCTs031180007.
- Cervical Cancer
Data availability statement
Data are available upon reasonable request.
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Collaborators On behalf of Gynecologic Cancer Study Group in Japan Clinical Oncology Group.
Contributors MI, MT, HK, and NY contributed to study conceptualization, study design, data interpretation, and manuscript preparation. JCOG Data Center and JCOG Operations Office contributed to quality control of the data and to data analysis. All the authors contributed to data acquisition, manuscript editing and manuscript review, and have approved this submission. MI is responsible for the overall content as guarantor.
Funding This work was supported by AMED under Grant Number JP16ck0106222 and JP19ck0106513 and by the National Cancer Center Research and Development Fund of Japan (23-A-17, 26-A-4, 29-A-3 and 2020-J-3).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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