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Chemo-Radiotherapy of Oligometastases of Colorectal Cancer With Pegylated Liposomal Mitomycin-C Prodrug (Promitil): Mechanistic Basis and Preliminary Clinical Experience

Hypo-fractionated radiotherapy and stereotactic body radiotherapy are viable options for treatment of oligometastases. A prodrug of mitomycin-C is under clinical testing as a pegylated liposomal formulation (Promitil) with an improved safety profile over mitomycin-C. Promitil was offered to two pati...

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Autores principales: Tahover, Esther, Bar-Shalom, Rachel, Sapir, Eli, Pfeffer, Raphael, Nemirovsky, Igor, Turner, Yehonatan, Gips, Maya, Ohana, Patricia, Corn, Benjamin W., Wang, Andrew Z., Gabizon, Alberto A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275313/
https://www.ncbi.nlm.nih.gov/pubmed/30534533
http://dx.doi.org/10.3389/fonc.2018.00544
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author Tahover, Esther
Bar-Shalom, Rachel
Sapir, Eli
Pfeffer, Raphael
Nemirovsky, Igor
Turner, Yehonatan
Gips, Maya
Ohana, Patricia
Corn, Benjamin W.
Wang, Andrew Z.
Gabizon, Alberto A.
author_facet Tahover, Esther
Bar-Shalom, Rachel
Sapir, Eli
Pfeffer, Raphael
Nemirovsky, Igor
Turner, Yehonatan
Gips, Maya
Ohana, Patricia
Corn, Benjamin W.
Wang, Andrew Z.
Gabizon, Alberto A.
author_sort Tahover, Esther
collection PubMed
description Hypo-fractionated radiotherapy and stereotactic body radiotherapy are viable options for treatment of oligometastases. A prodrug of mitomycin-C is under clinical testing as a pegylated liposomal formulation (Promitil) with an improved safety profile over mitomycin-C. Promitil was offered to two patients with oligometastases from colorectal cancer as radiosensitizer. Each derived durable clinical benefit from Promitil administered immediately prior to and following irradiation. Transient toxicity to normal tissues of moderate to severe degree was observed. Promitil appears to have potential clinical value in this setting. HIGHLIGHTS: - Delivery of radio-sensitizing drugs with pegylated (long-circulating) liposomes is a pharmacologically rational approach which remains largely clinically untested. - A mitomycin-c prodrug delivered by pegylated liposomes (Promitil) is activated by thiol groups, which are produced in excess by radiation-damaged cells, thus potentiating the radio-sensitizing effect of Promitil. - Two durable clinical responses in patient with colorectal oligometastases to Promitil and radiotherapy suggest that this approach may be of value in cancer chemo-radiotherapy.
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spelling pubmed-62753132018-12-10 Chemo-Radiotherapy of Oligometastases of Colorectal Cancer With Pegylated Liposomal Mitomycin-C Prodrug (Promitil): Mechanistic Basis and Preliminary Clinical Experience Tahover, Esther Bar-Shalom, Rachel Sapir, Eli Pfeffer, Raphael Nemirovsky, Igor Turner, Yehonatan Gips, Maya Ohana, Patricia Corn, Benjamin W. Wang, Andrew Z. Gabizon, Alberto A. Front Oncol Oncology Hypo-fractionated radiotherapy and stereotactic body radiotherapy are viable options for treatment of oligometastases. A prodrug of mitomycin-C is under clinical testing as a pegylated liposomal formulation (Promitil) with an improved safety profile over mitomycin-C. Promitil was offered to two patients with oligometastases from colorectal cancer as radiosensitizer. Each derived durable clinical benefit from Promitil administered immediately prior to and following irradiation. Transient toxicity to normal tissues of moderate to severe degree was observed. Promitil appears to have potential clinical value in this setting. HIGHLIGHTS: - Delivery of radio-sensitizing drugs with pegylated (long-circulating) liposomes is a pharmacologically rational approach which remains largely clinically untested. - A mitomycin-c prodrug delivered by pegylated liposomes (Promitil) is activated by thiol groups, which are produced in excess by radiation-damaged cells, thus potentiating the radio-sensitizing effect of Promitil. - Two durable clinical responses in patient with colorectal oligometastases to Promitil and radiotherapy suggest that this approach may be of value in cancer chemo-radiotherapy. Frontiers Media S.A. 2018-11-26 /pmc/articles/PMC6275313/ /pubmed/30534533 http://dx.doi.org/10.3389/fonc.2018.00544 Text en Copyright © 2018 Tahover, Bar-Shalom, Sapir, Pfeffer, Nemirovsky, Turner, Gips, Ohana, Corn, Wang and Gabizon. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Tahover, Esther
Bar-Shalom, Rachel
Sapir, Eli
Pfeffer, Raphael
Nemirovsky, Igor
Turner, Yehonatan
Gips, Maya
Ohana, Patricia
Corn, Benjamin W.
Wang, Andrew Z.
Gabizon, Alberto A.
Chemo-Radiotherapy of Oligometastases of Colorectal Cancer With Pegylated Liposomal Mitomycin-C Prodrug (Promitil): Mechanistic Basis and Preliminary Clinical Experience
title Chemo-Radiotherapy of Oligometastases of Colorectal Cancer With Pegylated Liposomal Mitomycin-C Prodrug (Promitil): Mechanistic Basis and Preliminary Clinical Experience
title_full Chemo-Radiotherapy of Oligometastases of Colorectal Cancer With Pegylated Liposomal Mitomycin-C Prodrug (Promitil): Mechanistic Basis and Preliminary Clinical Experience
title_fullStr Chemo-Radiotherapy of Oligometastases of Colorectal Cancer With Pegylated Liposomal Mitomycin-C Prodrug (Promitil): Mechanistic Basis and Preliminary Clinical Experience
title_full_unstemmed Chemo-Radiotherapy of Oligometastases of Colorectal Cancer With Pegylated Liposomal Mitomycin-C Prodrug (Promitil): Mechanistic Basis and Preliminary Clinical Experience
title_short Chemo-Radiotherapy of Oligometastases of Colorectal Cancer With Pegylated Liposomal Mitomycin-C Prodrug (Promitil): Mechanistic Basis and Preliminary Clinical Experience
title_sort chemo-radiotherapy of oligometastases of colorectal cancer with pegylated liposomal mitomycin-c prodrug (promitil): mechanistic basis and preliminary clinical experience
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275313/
https://www.ncbi.nlm.nih.gov/pubmed/30534533
http://dx.doi.org/10.3389/fonc.2018.00544
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