Open AccessPhase 1 study of veliparib with carboplatin and weekly paclitaxel in Japanese patients with newly diagnosed ovarian cancer
Author(s) -
Nishio Shin,
Takekuma Munetaka,
Takeuchi Satoshi,
Kawano Kouichirou,
Tsuda Naotake,
Tasaki Kazuto,
Takahashi Nobutaka,
Abe Masakazu,
Tanaka Aki,
Nagasawa Takayuki,
Shoji Tadahiro,
Xiong Hao,
Nuthalapati Silpa,
Leahy Terri,
Hashiba Hideyuki,
Kiriyama Tsukasa,
Komarnitsky Philip,
Hirashima Yasuyuki,
Ushijima Kimio
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13381
Subject(s) - carboplatin , veliparib , medicine , tolerability , neutropenia , paclitaxel , adverse effect , regimen , ovarian cancer , pharmacokinetics , gastroenterology , oncology , chemotherapy , cancer , cisplatin , biochemistry , polymerase , poly adp ribose polymerase , gene , chemistry
This phase 1, open‐label, dose‐escalation study was conducted to determine the safety, tolerability, pharmacokinetics and preliminary efficacy of veliparib with carboplatin and weekly paclitaxel in Japanese women with newly diagnosed, advanced ovarian cancer. Patients received veliparib at 100 or 150 mg b.i.d. on days 1–21 with carboplatin (area under the concentration–time curve 6 mg/mL•min) on day 1 and paclitaxel 80 mg/m 2 on days 1, 8 and 15 every 3 weeks for up to 6 21‐day cycles. Dose escalation followed a 3 + 3 design to determine dose‐limiting toxicities, maximum tolerated dose and the recommended phase 2 dose. Nine patients (median age 62 [range 27–72] years) received a median of 5 (range 3–6) cycles of treatment (3 at 100 mg, 6 at 150 mg). There were no dose‐limiting toxicities. The most common adverse events of any grade were neutropenia (100%), alopecia (89%), peripheral sensory neuropathy (78%), and anemia, nausea and malaise (67% each). Grade 3 or 4 adverse events were associated with myelosuppression. Pharmacokinetics of carboplatin/paclitaxel were similar at both veliparib doses. Response, assessed in five patients, was partial in four and complete in one (objective response rate 100%). The response could not be assessed in four patients who had no measurable disease at baseline. The recommended phase 2 dose of veliparib, when combined with carboplatin/paclitaxel, is 150 mg b.i.d. Findings from this phase 1 trial demonstrate the tolerability and safety of veliparib with carboplatin/paclitaxel, a regimen with potential clinical benefit in Japanese women with ovarian cancer.