sepantronium and Skin-Neoplasms

Melanoma continues to be a major health problem with no effective therapy. Melanocytes, both benign and malignant, express many anti-apoptotic factors. Survivin is a member of the family of inhibitors of apoptosis proteins (IAP) and is preferentially expressed in tumor cells, including melanoma. YM155 is a small molecule suppressant of survivin that has been shown in preclinical cell lines, xenograft models and phase I studies to have anti-tumor activity.. This was an open-label, multi-center, study of YM155 monotherapy in subjects with unresectable stage III or IV melanoma. Thirty-four chemotherapy naïve subjects were treated with YM155 at a dose of 4.8 mg/m(2)/day administered by continuous infusion for 168-hours (7 days) followed by a 14-day rest period, for up to 6 cycles or until disease progression.. One subject had a partial response to treatment seen at cycle two and lasting through cycle eight. Median progression-free survival was 1.3 months (95% CI; 1.3-2.7). Median overall survival was 9.9 months (95% CI; 7.0-14.5). Overall, YM155 was well tolerated with the most common (>20%) adverse events reported as fatigue, nausea, pyrexia, headache, arthralgia and back pain. Only four subjects required dose reductions.. YM155 was well tolerated in subjects with advanced melanoma; however, the pre-specified primary end-point for efficacy which required two responders in 29 evaluable subjects was not achieved.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Disease-Free Survival; Female; Humans; Imidazoles; Inhibitor of Apoptosis Proteins; Male; Melanoma; Microtubule-Associated Proteins; Middle Aged; Naphthoquinones; Neoplasm Staging; Skin Neoplasms; Survivin; Treatment Outcome

The development of vitiligo has been associated with an improved clinical response in melanoma patients.. We report a case of vitiligo associated with a novel antisurvivin drug and review the literature to determine the pathogenesis of vitiligo occurring during melanoma treatment.. A 78-year-old man with stage IV malignant melanoma developed vitiligo after the first therapeutic cycle of a novel antisurvivin drug. Although his vitiligo remained static, his melanoma continued to progress and he died in 8 months. A review of the literature demonstrates a relationship between vitiligo development and improved clinical response in many melanoma cases treated with immunotherapy; however, the relationship may depend on the type of treatment.. Understanding complex immune responses in vitiliginous skin and melanoma sites is important in order to interpret the development of vitiligo occurring during melanoma treatment.

Topics: Aged; Antineoplastic Agents; Humans; Imidazoles; Inhibitor of Apoptosis Proteins; Male; Melanoma; Microtubule-Associated Proteins; Naphthoquinones; Skin Neoplasms; Survivin; Vitiligo