Prospective Phase I Trial of Concurrent Full Dose Gemcitabine/Nab-paclitaxel and Ablative Radiation Therapy for Borderline and Locally Advanced Pancreatic Cancer
Kim H, Olsen JR, Wang-Gillam A, Green OL, Fields RC, Hammill C, Strasberg S, Doyle MB, Hawkins W, Suresh R, Tan B, Pedersen K, Henke LE, DeWees TA, Chapman W, Parikh PJ, and Roach MC. Prospective Phase I Trial of Concurrent Full Dose Gemcitabine/Nab-paclitaxel and Ablative Radiation Therapy for Borderline and Locally Advanced Pancreatic Cancer. Int J Radiat Oncol Biol Phys 2019; 105(1):S209-S210.
Int J Radiat Oncol Biol Phys
Purpose/Objective(s): MR guided online adaptive radiation (MRgRT) therapy may permit radiation therapy (RT) and chemotherapy dose escalation in patients with pancreatic cancer. The purpose of this study was to determine the maximum tolerated dose (MTD) of ablative hypofractionated RT with full dose gemcitabine/nab-paclitaxel (G/NP) in patients with unresectable pancreatic cancer. Materials/Methods: This single arm, phase I study included patients with borderline resectable or locally advanced pancreatic cancer. Patients were treated with G/NP (1000 mg/m2; 125 mg/m2) x 1 cycle. Those without disease progression were subsequently treated with concurrent G/NP and RT directed to pancreatic gross disease without elective nodal coverage. G/NP and RT doses were escalated per time-to-event continual reassessment method. Patients were initially treated to 40-45 Gy / 25 fxs with G/NP (600-800 mg/m2; 75 mg/m2) weeks 1, 2, 4 and 5. The protocol was amended in 8/2016 to 60-67.5 Gy / 15 fxs with MRgRT, and concurrent full dose G/NP (1000 mg/m2; 100 mg/m2) weeks 1 and 2. Patients were eligible for additional chemotherapy after G/NP-RT per physician discretion. Luminal bowel OARs were contoured daily for adaptive planning with V50 Gy < 0.5 cc. The primary endpoint was the MTD of RT as defined by 60-day dose limiting toxicity (DLT). DLT was treatment related grade 5, grade 4 hematologic or grade 3 GI requiring hospitalization > 3 days. Secondary endpoints included surgical resection rates, local control, progression free survival and OS. Results: Thirty patients were enrolled (3/2015-2/2019), with 26 evaluable patients (2 patients progressed prior to RT, 1 withdrew consent, 1 did not meet planning constraints). Regional lymphadenopathy was present in 54%. The only DLT was acute cholecystitis in a non-MRgRT treated patient prior to reaching 45 Gy / 25 fxs. The majority of patients (69.2%) were treated with full dose G/NP and the 67.5 Gy / 15 fxs level with an estimated DLT rate of 14.1% with 95% CI [3.3% to 24.9%]. At a median follow-up of 14 months, 16 patients have died. Six patients, one of which was initially locally advanced, underwent surgical resection (23%). Median OS is 14.3 months with 1-year OS of 68.7 [46.9% to 82.9%]. Seven patients (26.9%) had OS of greater than 25 months (25.7-43.5 months). Conclusion: Full dose G/NP with concurrent ablative RT doses is safe and well tolerated. These results stand in contrast to studies using ablative dose RT or concurrent RT and G/NP without MRgRT. Further follow-up and a phase II study are necessary to determine the disease related outcomes associated with ablative dose. [Figure presented]