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- Title
A phase I dose escalation trial of nab-paclitaxel and fixed dose radiation in patients with unresectable or borderline resectable pancreatic cancer.
- Authors
Shabason, Jacob E.; Chen, Jerry; Apisarnthanarax, Smith; Damjanov, Nevena; Giantonio, Bruce; Loaiza-Bonilla, Arturo; O’Dwyer, Peter J.; O’Hara, Mark; Reiss, Kim A.; Teitelbaum, Ursina; Wissel, Paul; Drebin, Jeffrey A.; Vollmer, Charles; Kochman, Michael; Mick, Rosemarie; Vergara, Norge; Jhala, Nirag; Doucette, Abigail; Lukens, John N.; Plastaras, John P.
- Abstract
<bold>Purpose: </bold>Patients with locally advanced pancreatic cancer typically have poor outcomes, with a median survival of approximately 16 months. Novel methods to improve outcomes are needed. Nab-paclitaxel (Abraxane) has shown efficacy in pancreatic cancer and is FDA-approved for metastatic disease in combination with gemcitabine. Nab-paclitaxel is also a promising radiosensitizer based on laboratory studies, but it has never been clinically tested with definitive radiotherapy for locally advanced pancreatic carcinoma.<bold>Methods: </bold>We performed a phase 1 study using a 3 + 3 dose escalation strategy to determine the safety and tolerability of dose-escalated nab-paclitaxel with fractionated radiotherapy for patients with unresectable or borderline resectable pancreatic cancer. Following induction chemotherapy with two cycles of nab-paclitaxel and gemcitabine, patients were treated with weekly nab-paclitaxel and daily radiotherapy to a dose of 52.5 Gy in 25 fractions. Final dose-limiting toxicity (DLT) determination was performed at day 65 after the start of radiotherapy.<bold>Results: </bold>Nine patients received nab-paclitaxel at a dose level of either 100 mg/m2 (n = 3) or 125 mg/m2 (n = 6). There were no observed grade 3 gastrointestinal toxicities. One DLT (grade 3 neuropathy) was observed in a patient who received 125 mg/m2 of nab-paclitaxel. Other grade 3 toxicities included fatigue (11%), anemia (11%) and neutropenia (11%). No grade 4 toxicities were observed. Following chemoradiotherapy, four patients (borderline resectable, n = 2 and unresectable, n = 2) underwent surgical resection, all with negative margins and with significant treatment effect with limited tumor viability.<bold>Conclusions: </bold>The combination of fractionated radiation and weekly full dose nab-paclitaxel was safe and well-tolerated.
- Subjects
PANCREATIC cancer treatment; PACLITAXEL; RADIOTHERAPY; DOSE-effect relationship in pharmacology; DOSE-response relationship (Radiation); HEALTH outcome assessment; PANCREATIC tumors; ANTINEOPLASTIC agents; DIARRHEA; NAUSEA; RESEARCH funding; ALBUMINS; TREATMENT effectiveness; DEOXYCYTIDINE; TUMOR treatment
- Publication
Cancer Chemotherapy & Pharmacology, 2018, Vol 81, Issue 3, p609
- ISSN
0344-5704
- Publication type
journal article
- DOI
10.1007/s00280-018-3519-6