Phase II study of thalidomide in patients with metastatic malignant melanoma
| Autor: | Gilberto Schwartsmann, Sabrina A. Fernandes, Marc François Richter, Anna Isabel Neto Cancela, Luciane Pons Di Leone, Teresa Dalla Costa, André Borba Reiriz |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Vascular Endothelial Growth Factor A Cancer Research medicine.medical_specialty Skin Neoplasms Maximum Tolerated Dose Administration Oral Phases of clinical research Angiogenesis Inhibitors Dermatology Pharmacology Gastroenterology Drug Administration Schedule Pharmacokinetics Internal medicine Humans Medicine Melanoma Survival rate Multiple myeloma Aged Temozolomide Neovascularization Pathologic business.industry Middle Aged medicine.disease Thalidomide Survival Rate Treatment Outcome Oncology Pharmacodynamics Toxicity Female Fibroblast Growth Factor 2 Neoplasm Recurrence Local business medicine.drug |
| Zdroj: | Melanoma Research. 14:527-531 |
| ISSN: | 0960-8931 |
| DOI: | 10.1097/00008390-200412000-00014 |
| Popis: | Thalidomide has anti-angiogenic and immunomodulatory activity, exhibiting antitumour effects in patients with multiple myeloma and, more rarely, in several other solid tumours. We evaluated the single-agent antitumour activity and toxicity profile of thalidomide in patients with metastatic malignant melanoma, as well as its plasma pharmacokinetics and pharmacodynamic effects [vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF) levels]. A two-stage Gehan method was used with a stopping rule after 14 consecutive non-responding patients. Thalidomide was given orally at a daily dose of 200 mg/day, which was then escalated every 2 weeks by 200 mg/day as tolerated to a maximum of 800 mg/day. Patients were evaluated every 8 weeks for response using the World Health Organization (WHO)-27 criteria. Fourteen patients were enrolled and no objective responses were observed, with one stable disease and one mixed response. The dose-limiting toxicities were constipation, dizziness and somnolence. Other toxicities were oedema, neuropathy, dry skin, dry mouth, tremor and fatigue. The plasma pharmacokinetics of thalidomide were comparable with those of previous studies in normal volunteers and in patients with advanced prostate cancer. Serum levels of b-FGF and VEGF did not change significantly following drug administration. In conclusion, thalidomide showed poor activity, but acceptable toxicity, in patients with metastatic melanoma. Future studies should explore this agent in combination with other biological agents or cytotoxic agents, such as temozolomide. |
| Databáze: | OpenAIRE |
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