Effect of bevacizumab on rate of oxaliplatin-induced thrombocytopenia and splenomegaly.

Abstract

3544 Background: Oxaliplatin-based chemotherapy can cause hepatic sinusoidal injury (HSI) leading to portal hypertension. This results in splenic sequestration of platelets and thrombocytopenia. Evidence suggests that bevacizumab may protect against HSI, although the clinical impact of this has not been well examined. The purpose of our study was to evaluate rate of thrombocytopenia and splenomegaly as clinical end-points indicative of bevacizumab mediated modulation of oxaliplatin-induced hepatic toxicity. Methods: We performed a retrospective review of metastatic colorectal cancer patients treated at M D Anderson Cancer Center from 1/2003 to 1/2010 with ≥ 3 months of frontline fluoropyrimidine and oxaliplatin (FOLFOX) with or without bevacizumab. Patients with prior liver disease, liver surgery or absence of spleen were excluded. Splenic volumes pre, during and post FOLFOX therapy were determined with CT scans and correlated with platelet counts and treatment. Results: A total of 184 patients [Bev cohort: FOLFOX/Bev (n =138); Non-Bev cohort: FOLFOX alone (n = 46)] were identified. Baseline characteristics (age, gender, spleen size and platelet counts) were similar in both groups. Median number of oxaliplatin cycles for each cohort was 9.00 (p = 0.9). The median total oxaliplatin dose did not differ between the two cohorts (p = 0.9). Development of splenomegaly (volume increase ≥ 30%) was more common in the Non-Bev cohort (48% vs. 32%; p = 0.013). The median time to develop splenomegaly was significantly longer in the Bev cohort (7.6 vs. 5.5 months; p = 0.023). Splenomegaly correlated with a higher rate of thrombocytopenia (defined as platelets < 150K) at 3 months (40% vs. 16%, p = 0.0005) and beyond (during 3 to 6 months of treatment, p < 0.0001). Correspondingly, bevacizumab therapy was associated with lower rates of thrombocytopenia at 3 months (24% in Bev cohort vs. 43% in Non-Bev cohort, p = 0.006) and beyond (p = 0.003). Conclusions: In our cohort, addition of bevacizumab to oxaliplatin chemotherapy reduces the occurrence of splenic enlargement, which correlates with a decreased rate of thrombocytopenia. Further studies to understand the potential hepato-protective mechanism of anti-VEGF therapy are needed.