A Phase I Study of Veliparib (ABT-888) in Combination with Low-Dose Fractionated Whole Abdominal Radiation Therapy in Patients with Advanced Solid Malignancies and Peritoneal Carcinomatosis

作者：Reiss Kim A; Herman Joseph M; Zahurak Marianna; Brade Anthony; Dawson Laura A; Scardina Angela; Joffe Caitlin; Petito Emily; Hacker Prietz Amy; Kinders Robert J; Wang Lihua; Chen Alice; Temkin Sarah; Horiba Naomi; Siu Lillian L; Azad Nilofer S^*

来源：Clinical Cancer Research, 2015, 21(1): 68-76.

DOI：10.1158/1078-0432.CCR-14-1552

Purpose: The combination of low-dose radiotherapy with PARP inhibition has been shown to enhance antitumor 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.
Experimental Design: Patients were treated with veliparib (80320 mg daily) for a total of 3 cycles. LDFWAR consisted of 21.6 Gy in 36 fractions, 0.6 Gy twice daily on days 1 and 5 for weeks 1-3of each cycle. Circulating tumor cells (CTC) were collected and evaluated for gamma-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 toxicities 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 weeks) was observed in 7 patients (33%). Median progressionfree survival (mPFS) was 4.47 months and median overall survival (mOS) was 13.04 months. In the subset of 8 ovarian and fallopian cancers, mPFS was 6.77 months and mOS was 17.54 months compared with mPFS 2.71 months and mOS 13.01 months in others. Patients with ovarian and fallopian cancers had better QoL over time than those with other cancers. An increased percentage of gamma-H2AX-positive CTCs was observed in a subset of patients (3/6 with > 2 CTCs at baseline).
Conclusions: Combined veliparib and LDFWAR is a welltolerated regimen that resulted in prolonged disease stability for some patients with advanced solid tumors and carcinomatosis, particularly in the ovarian and fallopian cancer subpopulation.

• 出版日期2015-1-1