RESUMEN
BACKGROUND/AIM: Temozolomide plays a role in treating melanoma refractory to immunomodulatory and mitogen-activated protein kinase-targeted approaches, but its efficacy is limited. 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a polychlorinated pyridine cholesteryl carbonate. Its mechanism of action is considered to be via alkylation/adduct formation with N7-guanine. It demonstrated activity in intracranial implanted human glioma and breast cancer xenograft mouse models. The activity of DM-CHOC-PEN in melanoma models was assessed. MATERIAL AND METHODS: B-16 melanoma cells were exposed to DM-CHOC-PEN at different concentrations to assess proliferation and survival. B-16 cells were implanted subcutaneously into the flank of adult female C57BL mice which were then were treated with 200 mg/kg DM-CHOC-PEN intraperitoneally daily for 5 days in the setting of palpable subcutaneous tumor. Survival was compared to mice treated with temozolomide or saline. Five mice were treated per group. RESULTS: In vitro, the respective half-maximal inhibitory concentrations of DM-CHOC-PEN and temozolomide were 0.5 and ≥3.0 µg/ml. Floating, heavily melanotic cells formed and these cells were separated, analyzed, and contained 10-90 ng DM-CHOC-PEN per 105 cells. The improvement in survival of mice treated with DM-CHOC-PEN or temozolomide relative to saline controls was 142% and 78%, respectively. CONCLUSION: Longer survival was seen with DM-CHOC-PEN in a C57BL murine model relative to temozolomide and saline-treated controls, supporting the development of clinical trials assessing the efficacy of DM-CHOC-PEN as treatment for metastatic melanoma.
Asunto(s)
Glioma , Melanoma , Adulto , Humanos , Femenino , Ratones , Animales , Temozolomida/farmacología , Temozolomida/uso terapéutico , Ratones Endogámicos C57BL , Antineoplásicos Alquilantes/uso terapéutico , Melanoma/tratamiento farmacológico , Melanoma/patología , Glioma/tratamiento farmacológicoRESUMEN
The authors describe the case of a patient who initially presented with uterine leiomyosarcoma (LMS) that later metastasized to the spine. The patient was treated at another institution for her primary uterine LMS, undergoing resection followed by adjuvant chemotherapy. After several years of disease remission, the patient presented in January 2011 to the authors' institution with recurrent uterine LMS metastatic to the spine, which has been treated with multiple therapeutic modalities in a combination of surgery, radiosurgery, and chemotherapy. As a result of this approach, the patient has been progression free for 35 months since her presentation (April 2011 to March 2014). We herein describe our experience treating this patient with recurrent uterine LMS of the spine and suggest that patients with recurrent uterine LMSs should be considered for treatment using a multimodality approach with emphasis on enrollment into clinical trials.