Use of bevacizumab to reduce the rate of oxaliplatin-induced thrombocytopenia and splenomegaly.

Abstract

564 Background: Oxaliplatin-based chemotherapy can cause hepatic sinusoidal injury (HSI), portal hypertension, and splenic sequestration of platelets. In the NSABP C-08 study a reduced rate of thrombocytopenia (1.4% vs 3.4%, P <0.01) was seen in the bevacizumab arm. Evidence suggests that bevacizumab may protect against HSI, though the clinical impact of this has not been well examined. Methods: A retrospective review of metastatic colorectal cancer patients treated at MD Anderson Cancer Center from 1/2003 to 1/2010 with ≥3 months of frontline fluoropyrimidine and oxaliplatin (FOLFOX) with or without bevacizumab was conducted. Presence of known liver disease, prior liver surgery, absence of spleen, or adjuvant oxaliplatin were exclusion criteria. Splenic volumes pre, during, and post FOLFOX treatment were determined from CT scans and correlated with platelet counts and treatment. Results: 184 pts (138 FOLFOX/Bev; 46 FOLFOX) were identified. The median number of cycles (9 for each cohort) and the total oxaliplatin dose (P = 0.78) did not differ between the two cohorts. The development of splenomegaly (spleen volume increase of ≥30%) was more common in the non-Bev cohort, 48% vs 32%, P=0.013. The median time to splenomegaly was longer in the Bev cohort, 7.6 vs 5.5 months, P=0.023. When comparing patients with and without splenomegaly, the presence of splenomegaly correlated with thrombocytopenia (<150 platelet count) at 3 months (40% vs. 16%, P=0.0005) and beyond (lower mean platelet counts during 3 to 6 months of treatment, P <0.0001 by Two-way ANOVA). A correlation with thrombocytopenia was also seen in the non-Bev vs. Bev cohort at both 3 months (43% vs 24%, P = 0.006) and beyond (P = 0.003). Conclusions: The addition of bevacizumab to oxaliplatin chemotherapy reduces the frequency of splenic enlargement, which directly correlates with a reduced rate of thrombocytopenia. Further study to understand the hepato-protective mechanism of anti-VEGF therapy is needed.