Direct effects of platinum-based chemotherapy ± bevacizumab on the bone metabolism of patients with primary and platinum-sensitive recurrent tuboovarian carcinoma

Background

Data regarding direct effects of antineoplastic chemotherapy (Ctx) on the bone metabolism of patients (pts) with epithelial tuboovarian carcinoma (ETOC) are largely lacking. The present translational project sought to gain detailed information on the influence of platinum-based Ctx ± bevacizumab (Bev) on the expression of various bone markers in pts with primary or platinum-sensitive recurrent ETOC.

Methods

85 ETOC pts receiving platinum-based Ctx apart from a clinical trial were analyzed. 16 pts also received Bev. The following bone markers were determined at baseline and prior to every subsequent Ctx cycle (C1-C6): C-terminal telopeptide of type I collagen (ICTP) as a marker of osteoclast function, N-terminal propeptide of type I collagen (P1NP) as a marker of osteoblast function, and alkaline phosphatase (AP). Results for C2-6 were calculated as percent of baseline values prior to C1. Changes of bone markers over time were analyzed using repeated measures analysis of variance (ANOVA) with p 

Results

350 Ctx cycles without and 87 with Bev were evaluated. In both groups of pts,, ICTP showed a constant decline beyond C2 to 76 percent of the baseline value without and 56 percent of the baseline value with Bev at C6. For Ctx alone, P1NP decreased immediately after C1 showing a plateau effect beyond C3 with 85 percent of the baseline level at minimum. For Ctx + Bev, P1NP values declined during the whole course of Ctx reaching 66 percent of the baseline level at C6 without any plateau effect. Adding Bev to Ctx resulted in a significantly stronger effect on both parameters (ICTP: p = 0.043, P1NP: p = 0.002). For AP, no significant changes were detected for both Ctx and Ctx + Bev, respectively.

Conclusions

Platinum-based Ctx for primary and platinum-sensitive recurrent ETOC resulted in a significant inhibition of osteoblast and (secondarily) osteoclast activity. This is the first study demonstrating that addition of Bev is likely to both increase and accelerate the negative effect of platinum-based Ctx on bone metabolism of pts with ETOC. Prospective clinical trials adding osteoprotective agents to Ctx for ETOC are strongly recommended.

Clinical trial identification

Legal entity responsible for the study

Deutsche Musterberufsornung für Ärzte, Deutsches Arzneimittelgesetz (AMG)

Funding

N/A

Disclosure

All authors have declared no conflicts of interest.