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
Shaare Zedek Medical Center, Jerusalem, Israel.
Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Front Oncol. 2018 Nov 26;8:544. doi: 10.3389/fonc.2018.00544. eCollection 2018.
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. - 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.
低分割放疗和立体定向体部放疗是治疗寡转移的可行选择。丝裂霉素-C的一种前药正在作为聚乙二醇化脂质体制剂（Promitil）进行临床试验，其安全性优于丝裂霉素-C。Promitil被提供给两名患有结直肠癌寡转移的患者作为放射增敏剂。每位患者在放疗前后立即给予Promitil均获得了持久的临床益处。观察到对正常组织有中度至重度的短暂毒性。Promitil在这种情况下似乎具有潜在的临床价值。 - 用聚乙二醇化（长循环）脂质体递送放射增敏药物是一种药理学上合理的方法，但在很大程度上仍未经过临床测试。- 聚乙二醇化脂质体递送的丝裂霉素-c前药（Promitil）被硫醇基团激活，而硫醇基团由受辐射损伤的细胞过量产生，从而增强了Promitil的放射增敏作用。- 两名结直肠癌寡转移患者对Promitil和放疗产生了持久的临床反应，表明这种方法在癌症放化疗中可能具有价值。
