Effects of combined sunitinib and extracranial stereotactic radiotherapy on bone marrow hematopoiesis

There is considerable interest in deploying stereotactic body radiotherapy in combination with immune therapy for patients with extracranial oligometastases. In addition to angiogenesis inhibition, sunitinib appears to mediate antitumor immunity through effects on circulating monocytic cells. The current study investigated the effects of combined sunitinib and stereotactic radiotherapy on hematopoiesis. As part of a phase I/II clinical trial utilizing concurrent sunitinib (25-50 mg on days 1-28) and image-guided radiation therapy (40-50 Gy in 10 fractions starting on days 8-19) for patients with metastatic cancer, the complete blood count, platelet count and automatic differential were performed pretreatment and on days 8 and 19. On average, sunitinib monotherapy for 7 days resulted in a 33% decrease in monocytes and an 18% decrease in neutrophils (P<0.01 for all). Compared to sunitinib alone, combined sunitinib and radiation resulted in a further decrease in neutrophils, lymphocytes and platelets (P<0.05). Following sunitinib and radiation treatment, a greater than average decrease in monocytes (≥200/µl) was associated with a significant increase in progression-free and overall survival times. This exploratory study provides further evidence that monocytes represent a potential biomarker in patients with solid tumors treated with sunitinib.