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

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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, nonmetastatic 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 × 109 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.

Original languageEnglish (US)
Pages (from-to)1175-1178
Number of pages4
JournalInternational Journal of Radiation Oncology Biology Physics
Volume100
Issue number5
DOIs
StatePublished - Apr 1 2018

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Anus Neoplasms
Listeria
Mitomycin
Fluorouracil
Immunotherapy
cancer
Radiation
radiation
toxicity
dosage
radiation therapy
grade
Radiotherapy
Sigmoidoscopy
Chills
pain
Hyponatremia
Listeria monocytogenes
Back Pain
progressions

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

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

In: International Journal of Radiation Oncology Biology Physics, Vol. 100, No. 5, 01.04.2018, p. 1175-1178.

Research output: Contribution to journalArticle

Safran, H, Leonard, KL, Perez, K, Vrees, M, Klipfel, A, Schechter, S, Oldenburg, N, Roth, L, Shah, N, Rosati, K, Rajdev, L, Mantripragada, K, Sheng, IY, Barth, P & DiPetrillo, TA 2018, 'Tolerability of ADXS11-001 Lm-LLO Listeria-Based Immunotherapy With Mitomycin, Fluorouracil, and Radiation for Anal Cancer', International Journal of Radiation Oncology Biology Physics, vol. 100, no. 5, pp. 1175-1178. https://doi.org/10.1016/j.ijrobp.2018.01.004
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. / Tolerability of ADXS11-001 Lm-LLO Listeria-Based Immunotherapy With Mitomycin, Fluorouracil, and Radiation for Anal Cancer. In: International Journal of Radiation Oncology Biology Physics. 2018 ; Vol. 100, No. 5. pp. 1175-1178.
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abstract = "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, nonmetastatic 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 × 109 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.",
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AU - Safran, Howard

AU - Leonard, Kara Lynne

AU - Perez, Kimberly

AU - Vrees, Matthew

AU - Klipfel, Adam

AU - Schechter, Steven

AU - Oldenburg, Nicklas

AU - Roth, Leslie

AU - Shah, Nishit

AU - Rosati, Kayla

AU - Rajdev, Lakshmi

AU - Mantripragada, Kalyan

AU - Sheng, Iris Y.

AU - Barth, Peter

AU - DiPetrillo, Thomas A.

PY - 2018/4/1

Y1 - 2018/4/1

N2 - 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, nonmetastatic 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 × 109 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.

AB - 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, nonmetastatic 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 × 109 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.

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