High activity of sequential low dose chemo-modulating Temozolomide in combination with Fotemustine in metastatic melanoma. A feasibility study

Metastatic melanoma (MM) is an incurable cancer with poor prognosis. Preclinical and clinical experiences support the concept that continuous exposure to low-dose alkilating agent Temozolomide (TMZ) can deplete cells of the DNA repair enzyme O6-methylguanine-DNA-methyltransferare (MGMT) which is the primary mechanism of tumor resistance to alkylating agents like nitrosureaa Fotemusrine (FM). Our study valued the hypothesis that depletion of MGMT induced by TMZ could render melanoma cells more susceptible to FM. Since no data exist regarding the optimal timing, doses and schedules of this association, we investigated two different schedules as first line therapy in MM to verify the safety, feasibility and tumor response. This is the first clinical experience in MM using sequential non-therapeutic dose TMZ previous FM.