Effect of carboplatin dose capping on survival in recurrent breast, ovary and head and neck cancers: a single institutional retrospective study.

Introduction: Carboplatin based regimens are an integral part of chemotherapy regimens for recurrent head and neck cancers (rHNC), triple negative breast cancers (rTNBC) and ovarian cancers (rOC). Dose reduction/capping of carboplatin remains a controversial aspect of such regimens in patients with moderate creatinine clearance (50 ml/min to 125 ml/min), especially in resource limited setting. The authors, therefore, looked into the magnitude of difference in outcome this makes in the above mentioned subsites.

Methods: This single institutional retrospective study was performed with a total of 120 patients divided equally into Group A (patients receiving capped dose) and Group B (patients receiving uncapped dose). Further matching was performed with respect to age, sex, body surface area, weight, and primary malignancy subsite and baseline creatinine clearance. Patients in Group A had received 450 mg (for AUC 6 regimens) and 150 mg (for AUC 2 regimens) of carboplatin while patients in Group B received the actual calculated dose of carboplatin determined by the Calvert formula. Median progression free survival (mPFS) and median overall survival (mOS) were the co-primary outcome measures.

Results: At a median follow-up of 24 months, compared to Group A, Group B had a higher mPFS and mOS by 4 months (p < .001) and 5.5 months (p < .001), respectively. Statistically significant difference in outcome favouring Group B extends to all primary tumour subsites, with mPFS difference being 3.1 months (rHNC), 5.1 months (rTNBC) and 4.5 months (rOC) and mOS difference being 4.2 months (rHNC), 3 months (rTNBC) and 5.6 months (rOC). It was also found that capping had a statistically significant detriment in distal failure (p = .042) compared to locoregional failure (p = .842). A higher proportion of hematotoxicity was found in Group B, however, it was not statistically significant and well manageable.

Conclusions: Blatant dose capping of carboplatin should be avoided probably with more caution in patients with distant disease recurrence compared to their counterparts with locoregional failure.