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 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.

Doxil-induced regression of pleuro-pulmonary metastases in a patient with malignant meningioma.

Metastatic meningioma is a rare disease, which has no effective chemotherapy. We report on a treatment of this condition with Doxil, a liposomal doxorubicin formulation. A 60-year-old woman with massive pleuro-pulmonary metastases from recurrent cranial meningioma was treated with Doxil (50-37.5 mg/m2) for 18 months with near-complete resolution of metastases and disappearance of pleural fluid. The only significant toxicities observed were stomatitis and hand-foot syndrome, which resolved with dose reduction and increase of dosing intervals. Doxil was cleared very slowly in this patient with a monoexponential half-life of 108 h. The patient remains in near-complete response for 6 months after treatment discontinuation. This is the first report on an effective chemotherapy in a patient with typical metastatic meningioma. The exact mechanism accounting for such an effective drug action is not clear, but may be related to a particularly high microvascular permeability to the liposome carriers in these metastatic lesions.