Discussion
toxicity, platinum-sensitive ovarian cancer
DISEASE, MINOR, ADVERSE EVENT
This article presents the intermittent veliparib dosing of NCI 7977, a multicohort phase I clinical trial evaluating the safety and efficacy of the combination of veliparib and irinotecan. The safety findings revealed the MTD for the intermittent dosing cohort to be veliparib 50 mg twice daily on days 1–4 and 8–11 with irinotecan 100 mg/mThere have been other recent studies that have combined veliparib with similar multiagent chemotherapy, which included irinotecan. A phase I study of veliparib in combination with 5-fluorouracil (5-FU), leucovorin, and irinotecan (FOLFIRI) revealed the RP2D to be veliparib 200 mg twice a day with standard dose FOLFIRI (irinotecan 180 mg/mOne of the major limitations of our study is the small sample size. Because toxicity concerns, and accounting for the balance of the adverse event profile and limited efficacy, the dose expansion for the higher dose intermittent veliparib dosing was not pursued. This prevents us from any clear efficacy assessments, although the 4 patients had at least minor radiographic improvements with prolonged stable disease, despite the heavily pretreated patient population and 40% of patients having received prior irinotecan. Another limitation is our use of veliparib as a PARPi, which is less potent for PARP trapping compared with other PARPis (Our experience revealed enhanced toxicity with cytotoxic chemotherapy + PARPi combinations, and the lack of improved benefit compared with chemotherapy alone by other studies suggests more novel PARPi combinations may be preferred. For example, agents with nonoverlapping toxicity profiles such as the VEGF inhibitor bevacizumab and the PARPi olaparib. The combination of bevacizumab and olaparib is well tolerated and superior to bevacizumab alone in platinum-sensitive ovarian cancer, although it is unknown whether this is superior to olaparib monotherapy (In conclusion, the MTD of intermittent veliparib is 50 mg twice daily on days 1–4 and 8–11 with weekly irinotecan 100 mg/m