title: Phase II study of thalidomide in patients with metastatic malignant melanoma.
abstract: 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.
authors.affiliation: South American Office for Anticancer Drug Development, Porto Alegre, RS, Brazil. reiriz@terra.com.br
authors.forename: André B
authors.initials: AB
authors.lastname: Reiriz
authors.forename: Marc F
authors.initials: MF
authors.lastname: Richter
authors.forename: Sabrina
authors.initials: S
authors.lastname: Fernandes
authors.forename: Anna I
authors.initials: AI
authors.lastname: Cancela
authors.forename: Teresa D
authors.initials: TD
authors.lastname: Costa
authors.forename: Luciane P
authors.initials: LP
authors.lastname: Di Leone
authors.forename: Gilberto
authors.initials: G
authors.lastname: Schwartsmann
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D020714:Maximum Tolerated Dose; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D013792:Thalidomide / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D013792:Thalidomide