A phase 1 dual-dose escalation study of radiation and nab-paclitaxel in patients with unresectable and borderline resectable pancreatic cancer

Abstract

Background: This phase 1 dual dose-escalation study aimed to evaluate the safety, feasibility, and toxicity profile of combining dose-escalated radiation therapy with high-dose nab-paclitaxel in patients with unresectable or borderline resectable pancreatic cancer.

Methods and materials: Twenty-one evaluable patients were enrolled and allocated three radiation dose levels, 55 Gy, 57.5 Gy, and 60 Gy, administered over 5 weeks in 25 fractions. Concurrent nab-paclitaxel was given weekly at a dose of 125 mg/m². Radiation dose escalation was guided by a time-to-event continual reassessment method. Toxicities were classified according to CTCAE v4.0, with dose-limiting toxicities (DLT) defined as grade 3 or higher gastrointestinal events or substantial decline in performance status. Surgical resection was pursued in patients achieving sufficient tumor downstaging.

Results: Hematologic toxicities were the most common grade ≥3 adverse events occurring in 76.2% of patients. Nonhematologic toxicities were less frequent (57.1%). Two grade 3 gastrointestinal DLT cases occurred at dose levels 57.5 Gy and 60 Gy. The maximum tolerated dose was 60 Gy with a probability of DLT of 0.155 at this dose. Surgical resection with negative margins was achieved in 33.3% of patients, including all borderline resectable cases and 22.2% of initially unresectable cases. The median overall survival and time to local progression from the start of radiation therapy were 22.3 months and 20.3 months, respectively.

Conclusions: This study demonstrates the feasibility and safety of combining dose-escalated radiation with high-dose nab-paclitaxel in locally advanced pancreatic cancer. The regimen is associated with manageable toxicity and promising local control and survival.

Keywords: dose escalation; nab‐paclitaxel; pancreatic cancer; radiation therapy.