MR-guided radiation therapy with concurrent gemcitabine / nab-paclitaxel chemotherapy in inoperable pancreatic cancer: a TITE-CRM phase I trial
Kim H, Olsen JR, Green OL, Chin RI, Hawkins WG, Fields RC, Hammill C, Doyle MB, Chapman W, Suresh R, Tan B, Pedersen K, Jansen B, DeWees TA, Lu E, Henke LE, Badiyan S, Parikh PJ, Roach MC, Wang-Gillam A, and Lim KH. MR-guided radiation therapy with concurrent gemcitabine / nab-paclitaxel chemotherapy in inoperable pancreatic cancer: a TITE-CRM phase I trial. Int J Radiat Oncol Biol Phys 2022.
International journal of radiation oncology, biology, physics
BACKGROUND: Ablative radiation therapy for borderline resectable or locally advanced pancreatic ductal adenocarcinoma (BR/LA-PDAC) may limit concurrent chemotherapy dosing and usually is only safely deliverable to tumors distant from gastrointestinal organs. MR-guided radiation therapy (MRgRT) may safely permit radiation and chemotherapy dose escalation.
METHODS: We conducted a single-arm phase I study to determine the maximum tolerated dose (MTD) of ablative hypofractionated radiation with full-dose gemcitabine/nab-paclitaxel in patients with BR/LA-PDAC. Patients were treated with gemcitabine/nab-paclitaxel (1000/125 mg/m(2)) x 1c then concurrent gemcitabine/nab-paclitaxel and radiation. Gemcitabine/nab-paclitaxel and radiation doses were escalated per time-to-event continual reassessment method from 40-45 Gy / 25 fxs with chemotherapy (600-800/75 mg/m(2)) to 60-67.5 Gy / 15 fractions and concurrent gemcitabine/nab-paclitaxel (1000/100 mg/m(2)). The primary endpoint was MTD of radiation as defined by 60-day dose limiting toxicity (DLT). DLT was treatment-related G5, G4 hematologic or G3 gastrointestinal requiring hospitalization >3 days. Secondary endpoints included resection rates, local progression free survival (LPFS), distant metastasis free survival (DMFS), and overall survival (OS).
RESULTS: Thirty patients enrolled (3/2015-2/2019), with 26 evaluable patients (2 progressed before radiation, 1 determined ineligible for radiation during planning, 1 withdrew consent). One DLT was observed. The DLT rate was 14.1% [3.3%-24.9%] with a maximum tolerated dose of gemcitabine/nab-paclitaxel (1000/100 mg/m(2)) and 67.5 Gy / 15 fractions. At a median follow-up of 40.6 months for living patients the median OS was 14.5 months (95% CI, 10.9-28.2 months). The median OS for patients with ECOG 0 and CA 19-9 <90 were 34.1 (95% CI, 13.6-54.1) and 43.0 (95% CI, 8.0-not reached) months, respectively. 2-year LPFS and DMFS were 85% (95% CI, 63-94%) and 57% (95% CI, 34-73%), respectively.
CONCLUSIONS: Full-dose gemcitabine/nab-paclitaxel with ablative MRgRT dosing is safe in patients with BR/LA-PDAC, with promising LPFS and DMFS.
CLINICALTRIALS: gov NCTXXXXXXXX.
ePub ahead of print