No abstract

Background The combination of low-dose radiation therapy with poly (ADP-ribose) polymerase (PARP) inhibition has been shown to enhance anti-tumor efficacy through potentiating DNA damage. We combined low-dose fractionated whole abdominal radiation (LDFWAR) with escalating doses of veliparib (ABT-888), a small molecule PARP inhibitor, in patients with peritoneal carcinomatosis from advanced solid tumor malignancies. Methods Patients were treated with veliparib (80mg-320mg daily) for a total of 3 cycles. LDFWAR consisted of 21.6Gy in 36 fractions, 0.6 Gytwice daily on days 1 and 5 for weeks 1-3 of each cycle. Circulating tumor cells (CTCs) were collected and evaluated for γ-H2AX. Quality of life (QoL) was assessed using the EORTC-QLQ-C30 questionnaire. Results Twenty-two patients were treated. Treatment-related grade 3 and 4 toxicites included lymphopenia (68%), anemia (9%), thrombocytopenia (14%), neutropenia (4%), leukopenia (9%), ascites (4%), vomiting (4%) and dyspnea (4%). No objective responses were observed. Disease stabilization (≥24 wks) was observed in 7 patients (33%). Median PFS was 4.47 months and mOS was 13.04 months. In the subset of 8 ovarian and fallopian cancers (OV), mPFS was 6.77 months and mOS was 17.54 months compared to mPFS 2.71 months and mOS 13.01 months in others. Patients with OV had better QoL over time than those with other cancers. An increased percentage of γ-H2AX-positive CTCs was observed in a subset of patients (3/6 with >2 CTCs at baseline). Conclusions Combined veliparib and LDFWAR is a well-tolerated regimen that resulted in prolonged disease stability for some patients with advanced solid tumors and carcinomatosis, particularly in the OV subpopulation.

Background-The combination of low-dose radiation therapy with PARP inhibition enhances anti-tumor efficacy through potentiating DNA damage. We combined low-dose fractionated whole abdominal radiation (LDFWAR) with ABT-888 in patients with peritoneal carcinomatosis with a dose escalation in ovarian and fallopian cancer patients (OV).