Switching from standard to dose-dense chemotherapy in front-line treatment of advanced ovarian cancer: a retrospective study of feasibility and efficacy

Background: Current standard neoadjuvant treatment for advanced ovarian cancer is 3-weekly platinum-based chemotherapy (CP3w). Patients unable to have interval debulking surgery (IDS) or with significant residual disease have a poor outcome to CP3w treatment. We investigated the outcome in patients who were switched to dose-dense chemotherapy.

Methods: We retrospectively analysed 30 patients treated at UCLH in 2009-2013, who switched to dose-dense chemotherapy after neoadjuvant CP3w, having achieved a poor response/progressed and unable to proceed to IDS (n=21), or had >1 cm residual disease after IDS (n=9). Treatment was 3-weekly carboplatin and weekly paclitaxel (n=23), or both drugs weekly (n=7). For comparison, we included 30 matched patients treated with CP3w followed by IDS (n=24, without or ≤1 cm residual disease; n=6, with >1 cm residual disease). Time to progression (TTP) and overall survival (OS) were measured from the date of diagnosis until progression (CT scan or CA-125) and death from any cause, respectively.

Results: Baseline characteristics were similar in both groups. The response rate to dose-dense chemotherapy was 70% (Gynecological Cancer Intergroup criteria). In the dose-dense group, 24 patients had tumour progression and 16 died; the corresponding numbers in the control group were 24 and 11. Median TTP was 15.8 months with dose-dense therapy, higher than expected for this patient group, and the same as in the control group (15.7 months) undergoing IDS, p=0.27. Median TTP in patients with residual disease postsurgery was 16.5 months (dose-dense) and 10.8 months (controls), p=0.02. TTP in dose-dense patients who did not have surgery was 10.4 months. Median OS was 31.3 (dose-dense) and 59.6 months (controls), p=0.06. Dose-dense chemotherapy was well tolerated: only three patients interrupted treatment due to toxicity.

Conclusion: Switching to dose-dense chemotherapy in patients who failed to respond to CT3w neoadjuvant chemotherapy appears to be an effective strategy and requires further investigation.