Weekly Carboplatin and Paclitaxel: A Retrospective Comparison with the Three-Weekly Schedule in First-Line Treatment of Ovarian Cancer

Abstract

Background: Conventional first-line combination therapy for ovarian cancer comprises 6 cycles of adjuvant or neoadjuvant carboplatin (AUC5-6) with paclitaxel (175 mg/m² ) every 3 weeks (PC-3W). Weekly scheduling of paclitaxel may maximize its antiangiogenic effect and reduce adverse effects. We compared the efficacy and safety of PC-3W with a modified protocol of weekly paclitaxel 80 mg/m² and weekly carboplatin AUC2 administered on days 1, 8, and 15 in a 28-day cycle (i.e., with 1 week off-treatment [PC-W]).

Materials and methods: Medical records of consecutive patients treated between 2000 and 2018 were reviewed; 707 patients were analyzed for demographic and clinical characteristics, effectiveness and toxicity.

Results: PC-3W was administered to 402 patients (median age, 60.5 years) and PC-W to 305 patients (median age, 62.5 years). Most patients (91.4%) were diagnosed at stage III-IV. Notwithstanding a higher proportion of residual disease and older patients in the PC-W group, median progression-free survival was 21.4 months and 13.2 months for PC-W and PC-3W, respectively; median overall survival was 75.2 and 54.0 months for PC-W and PC-3W, respectively. Cox proportional hazards model indicated improved survival for patients treated with PC-W (hazard ratio, 0.54). Similar results were observed for older patients diagnosed at ≥75 years. PC-W demonstrated a better safety profile, with lower incidence of neuropathy, neutropenia, and alopecia.

Conclusion: PC-W is as active and better tolerated than the standard PC-3W regimen. PC-W may serve as an alternative option for elderly or frail patients.

Implications for practice: Weekly scheduling of paclitaxel 80 mg/m² and carboplatin AUC2, administered on days 1, 8, and 15 in a 28-day cycle (PC-W) for first-line therapy for advanced ovarian cancer, is as active and better tolerated than the standard regimen of carboplatin and paclitaxel (175 mg/m² ) every 3 weeks (PC-3W). It is possible that the weekly holiday on day 21 in the PC-W regimen may ensure better completion rates (which may result in treatment delays for toxicity in PC-3W). The results of this retrospective analysis highlight the weekly regimen as a valid treatment option, especially for elderly patients and those with significant comorbidities.

Keywords: Carboplatin; Carcinoma; Ovarian epithelial; Paclitaxel; Weekly.

Figure 1

Kaplan‐Meier curves of progression‐free survival (PFS) according to the time interval from initiation of treatment. Weekly: neoadjuvant carboplatin (AUC2) and paclitaxel (80 mg/m²) administered on days 1, 8, and 15 in a 28‐day cycle, median PFS is 21.37 months (95% confidence interval [CI], 18.8–24.2; range, 0‐175.4). Three weekly: neoadjuvant carboplatin (AUC6) with paclitaxel (175 mg/m²) every 3 weeks, median PFS is 13.2 months (95% CI, 11.6–16.6; range, 0–188.9). Log‐rank p value <.001, n = 688.

Figure 2

Kaplan‐Meier curves of overall survival (OS) according to the time interval from initiation of treatment. Weekly: neoadjuvant carboplatin (AUC2) and paclitaxel (80 mg/m²) administered on days 1, 8, and 15 in a 28‐day cycle median, OS is 75.2 months (95% confidence interval [CI], 68.4–86.4; range, 2.7–211.5). Three weekly: neoadjuvant carboplatin (AUC6) with paclitaxel (175 mg/m²) every 3 weeks, median OS is 54.0 months (95% CI, 48.4–65.7; range, 0.0–249.0). Log‐rank p value <.001, n = 707.

Figure 3

Kaplan‐Meier curves of progression‐free survival (PFS) according to the time interval from initiation of treatment in patients diagnosed at ≥75 years. Weekly: neoadjuvant carboplatin (AUC2) and paclitaxel (80 mg/m²) administered on days 1, 8, and 15 in a 28‐day cycle, median PFS is 14.8 months (95% confidence interval [CI], 9.3–18.1; range, 0–99.2). Three weekly: neoadjuvant carboplatin (AUC6) with paclitaxel (175 mg/m²) every 3 weeks, median PFS is 6.1 months (95% CI, 4.5–9.3; range, 0–188.9). Log‐rank p value = .068, n = 83.

Figure 4

Kaplan‐Meier curves of overall survival (OS) according to the time interval from initiation of treatment in patients diagnosed at ≥75 years. Weekly: neoadjuvant carboplatin (AUC2) and paclitaxel (80 mg/m²) administered on days 1, 8, and 15 in a 28‐day cycle, median OS is 50.8 months (95% confidence interval [CI], 34.0–68.1; range, 7.3–109.0). Three weekly: neoadjuvant carboplatin (AUC6) with paclitaxel (175 mg/m²) every 3 weeks, median OS is 25.0 months (95% CI, 17.2–32.3; range, 5.0–194.9). Log‐rank p value = .024, n = 84.