Tolerability of ADXS11-001 Lm-LLO Listeria-Based Immunotherapy With Mitomycin, Fluorouracil, and Radiation for Anal Cancer

作者：Safran Howard^*; Leonard Kara Lynne; Perez Kimberly; Vrees Matthew; Klipfel Adam; Schechter Steven; Oldenburg Nicklas; Roth Leslie; Shah Nishit; Rosati Kayla; Rajdev Lakshmi; Mantripragada Kalyan; Sheng Iris Y; Barth Peter; DiPetrillo Thomas A

来源：International Journal of Radiation Oncology, Biology, Physics, 2018, 100(5): 1175-1178.

DOI：10.1016/j.ijrobp.2018.01.004

Purpose: To obtain safety and preliminary efficacy data of the combination of ADXS11-001, live attenuated Listeria monocytogenes bacterium, with mitomycin, 5-fluorouracil (5-FU), and intensity modulated radiation therapy in locally advanced anal cancer.
Patients and Methods: Eligibility included patients with previously untreated, non-metastatic anal cancer with a primary tumor >4 cm or node-positive disease. Patients received 2 cycles of mitomycin and 5-FU concurrent with 54.0 Gy intensity modulated radiation therapy. One intravenous dose of ADXS11-001 (1 x 10(9) colony-forming units) was administered before chemoradiation; 3 additional monthly doses were given after chemoradiation.
Results: Ten patients were treated, including 1 with N2 and 4 with N3 disease. Two patients had grade 3 acute toxicities after the initial dose of ADXS11-001, including chills/rigors (n = 2), back pain (n = 1), and hyponatremia (n = 1). All ADXS11-001 toxicities occurred within 24 hours of administration. There was no apparent increase in chemoradiation toxicities or myelosuppression. One patient had a grade 5 cardiopulmonary event shortly after beginning 5-FU treatment. All 9 assessable patients had complete clinical responses by sigmoidoscopy. Eight of 9 patients (89%) are progression-free at a median follow-up of 42 months.
Conclusions: Preliminary data show that ADXS11-001 can be safely administered with standard chemoradiation for anal cancer. Further studies of listeria-based immunotherapy with radiation are warranted.

• 出版日期2018-4-1