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- Title
A phase I trial of intraperitoneal nab-paclitaxel in the treatment of advanced malignancies primarily confined to the peritoneal cavity.
- Authors
Cristea, Mihaela C.; Frankel, Paul; Synold, Timothy; Rivkin, Saul; Lim, Dean; Chung, Vincent; Chao, Joseph; Wakabayashi, Mark; Paz, Benjamin; Han, Ernest; Lin, Paul; Leong, Lucille; Hakim, Amy; Carroll, Mary; Prakash, Neal; Dellinger, Thanh; Park, Min; Morgan, Robert J.
- Abstract
<bold>Purpose: </bold>To evaluate intraperitoneal (IP) nab-paclitaxel in patients with advanced malignancies that are primarily confined to the peritoneal cavity in a phase I trial.<bold>Methods: </bold>Using a 3 + 3 dose escalation of IP nab-paclitaxel on days 1, 8, and 15 of a 28-day cycle, we evaluated six dose levels (35-175 mg/m2/dose). Maximum tolerated dose (MTD) and pharmacokinetics (PK) of IP nab-paclitaxel were determined.<bold>Results: </bold>There were no dose-limiting toxicities (DLTs) in cohorts 1-3. There was a DLT in one of six patients in cohort 4 (112.5 mg/m2) (grade 3 neutropenia causing treatment delay > 15 days) and a DLT in one of three patients in cohort 6 (175 mg/m2) (grade 4 neutropenia and grade 3 abdominal pain). A second patient in cohort 6 experienced a serious adverse event (cycle 1, grade 4 ANC ≤ 7 days, cycle 4, grade 2 left ventricular dysfunction). This dose level was determined to be above the MTD. No DLTs were seen in seven patients treated in cohort 5 (140 mg/m2). The MTD of IP nab-paclitaxel was established at 140 mg/m2 on days 1, 8, and 15 of a 28-day cycle. There was a PK advantage for IP nab-paclitaxel, with an IP plasma area under the concentration-time curve (AUC) ratio of 147-fold (range 50-403) and therapeutic range systemic drug levels. Eight of 27 enrolled patients had progression-free survival ≥ 6 months. One patient experienced complete response, and one patient experienced partial response. Six patients had stable disease.<bold>Conclusions: </bold>Weekly IP nab-paclitaxel has a favorable toxicity profile, a significant pharmacologic advantage, and promising clinical activity.<bold>Clinical Trial Registration: </bold>NCT00825201.
- Subjects
PERITONEAL cancer; OVARIAN cancer; HYPERTHERMIC intraperitoneal chemotherapy; PACLITAXEL; TOXICITY testing
- Publication
Cancer Chemotherapy & Pharmacology, 2019, Vol 83, Issue 3, p589
- ISSN
0344-5704
- Publication type
journal article
- DOI
10.1007/s00280-019-03767-9