ABSTRACT
Treatment with ipilimumab, a monoclonal antibody that antagonizes cytotoxic T-lymphocyte antigen-4 (CTLA-4), results in improved survival of patients with stage IIIc-IV melanoma. However, there is a lack of data on the efficacy of ipilimumab in patients with brain metastases. To evaluate the efficacy of ipilimumab for the treatment of brain metastasis in melanoma, a multicentre, retrospective analysis of 38 patients with brain metastases in melanoma, treated with ipilimumab in the context of the French Expanded Access Program, was performed. Three patients had a 3 partial response, 5 stable disease, 15 disease progression and 15 patients died during the induction phase due to disease progression. Median overall survival was 101 days (range 54-154). The brain metastases control rate was 16% (6/38). Ipilimumab may be effective in a few patients with central nervous system metastasis. However, patients with brain metastases and a low life expectancy may not benefit sufficiently from treatment with ipilimumab.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Brain Neoplasms/drug therapy , Melanoma/drug therapy , Skin Neoplasms/pathology , Antibodies, Monoclonal/adverse effects , Antineoplastic Agents/adverse effects , Brain Neoplasms/secondary , Disease Progression , Female , Humans , Ipilimumab , Kaplan-Meier Estimate , Male , Melanoma/secondary , Retrospective Studies , Treatment OutcomeABSTRACT
Vemurafenib and erlotinib are two oral kinase inhibitors approved for the treatment of metastatic melanoma and advanced non-small cell lung cancer, respectively. In contrast with erlotinib, the single published method for analysis of vemurafenib in human plasma is based on mass spectrometry. The purpose of the present study was to develop an HPLC-UV method to simultaneously quantify these two drugs in plasma. Following liquid-liquid extraction, vemurafenib, erlotinib and sorafenib (internal standard) were separated isocratically on a C8 Xterra(®) MS using a mobile phase of glycine buffer (pH 9.0, 100mM)/acetonitrile (45:55, v/v). Samples were eluted at a flow rate of 0.9mL/min throughout the 12-min run. Dual UV wavelength mode was used, with vemurafenib and sorafenib monitored at 249nm, and erlotinib at 331nm. The calibration was linear in the range 1.25-100mg/L and 50-4000µg/L for vemurafenib and erlotinib, respectively. Inter- and intra-day precision was less than 6.7% and 6.6% for vemurafenib and erlotinib, respectively. This analytical method was successfully applied to assess the steady state plasma exposure of these drugs in cancer patients. This accurate method can be used in routine clinical practice to monitor vemurafenib or erlotinib concentrations in plasma from cancer patients.