ABSTRACT
Metastatic melanoma cells express a number of protein tyrosine kinases (PTKs) that are considered to be targets for imatinib. We conducted a phase II trial of imatinib in patients with metastatic melanoma expressing at least one of these PTKs. Twenty-one patients whose tumours expressed at least one PTK (c-kit, platelet-derived growth factor receptors, c-abl, or abl-related gene) were treated with 400 mg of imatinib twice daily. One patient with metastatic acral lentiginous melanoma, containing the highest c-kit expression among all patients, had dramatic improvement on positron emission tomographic scan at 6 weeks and had a partial response lasting 12.8 months. The responder had a substantial increase in tumour and endothelial cell apoptosis at 2 weeks of treatment. Imatinib was fairly well tolerated: no patient required treatment discontinuation because of toxicity. Fatigue and oedema were the only grade 3 or 4 toxicities that occurred in more than 10% of the patients. Imatinib at the studied dose had minimal clinical efficacy as a single-agent therapy for metastatic melanoma. However, based on the characteristics of the responding tumour in our study, clinical activity of imatinib, specifically in patients with melanoma with certain c-kit aberrations, should be examined.
Subject(s)
Antineoplastic Agents/therapeutic use , Melanoma/drug therapy , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Skin Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Base Sequence , Benzamides , DNA Primers , Disease Progression , Female , Humans , Imatinib Mesylate , Male , Melanoma/blood supply , Melanoma/diagnostic imaging , Melanoma/secondary , Middle Aged , Piperazines/adverse effects , Positron-Emission Tomography , Pyrimidines/adverse effects , Skin Neoplasms/blood supply , Skin Neoplasms/diagnostic imaging , Skin Neoplasms/pathology , Treatment OutcomeABSTRACT
To determine whether texturing and coating have additive effects in promoting tissue integration and inhibiting fibrosis, we evaluated smooth silicone rubber (SSR), textured silicone rubber (TSR), porous silicone rubber (PSR), expanded polytetrafluoroethylene (ePTFE), and porous polyurethane (PPU) subcutaneous implants in eight minipigs. Some of the implants were coated with type IV collagen (Col) and/or fibronectin (Fn). At 6 months, we removed the implants and examined them microscopically. Texturing was more important than Col and Fn in reducing fibrosis and inflammation. The PSR yielded the best response, including reduced fibrosis and inflammation, satisfactory adherence, and no dystrophic mineralization.
