Temozolomide plus thalidomide in patients with advanced melanoma: Results of a dose-finding trial Journal Article

Authors: Hwu, W. J.; Krown, S. E.; Panageas, K. S.; Menell, J. H.; Chapman, P. B.; Livingston, P. O.; Williams, L. J.; Quinn, C. J.; Houghton, A. N.
Article Title: Temozolomide plus thalidomide in patients with advanced melanoma: Results of a dose-finding trial
Abstract: Purpose: To establish a safe and tolerated regimen of an oral cytotoxic agent, temozolomide, and a cytostatic agent, thalidomide, in patients with unresectable stage III or IV malignant melanoma. Patients and Methods: Patients with unresectable stage III or IV melanoma without brain metastases were entered successively onto four treatment cohorts: level 1, temozolomide 50 mg/m2/d for 6 weeks followed by a 4-week break; levels 2, 3, and 4, temozolomide 75 mg/m2/d for 6 weeks followed, respectively, by breaks of 4, 3, and 2 weeks. Thalidomide was started at 200 mg/d, and escalated to a maximum dose of 400 mg/d. Safety was assessed at weeks 2 and 4 and every 4 weeks thereafter; tumor response was evaluated every 8 to 10 weeks. Results: Twelve patients were enrolled, three on each cohort. Therapy was generally well tolerated on all of the treatment schedules. Thalidomide at a dose of 400 mg/d was well tolerated in patients younger than 70, and 200 mg/d was well tolerated in older patients. The most common adverse events were grade 2 or 3 constipation and neuropathy, which were attributed to thalidomide. Five major responses (one complete, four partial) were documented, all at dose levels 2 to 4. Three of the five responding patients were in the over-70 age group. The median duration of response was 6 months (range, 4 to 17+ months), and the median overall survival was 12.3 months (range, 4 to 19+ months). Conclusion: The combination of temozolomide and thalidomide was well tolerated and had antitumor activity in patients with advanced melanoma, including elderly patients over 70 years old. © 2002 by American Society of Clinical Oncology.
Keywords: adult; cancer survival; clinical article; controlled study; treatment outcome; aged; middle aged; survival rate; thalidomide; clinical trial; constipation; drug tolerability; fatigue; advanced cancer; diarrhea; drug safety; temozolomide; neurotoxicity; dacarbazine; melanoma; controlled clinical trial; leukopenia; neuropathy; antineoplastic combined chemotherapy protocols; deep vein thrombosis; antineoplastic activity; cytotoxicity; dose-response relationship, drug; abdominal pain; arthralgia; dyspnea; rash; brain metastasis; nausea and vomiting; headache; maximum tolerated dose; dry skin; dose calculation; visual impairment; cytostasis; humans; human; male; female; priority journal; article
Journal Title: Journal of Clinical Oncology
Volume: 20
Issue: 11
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2002-06-01
Start Page: 2610
End Page: 2615
Language: English
DOI: 10.1200/jco.2002.09.034
PUBMED: 12039921
PROVIDER: scopus
Notes: Export Date: 14 November 2014 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Jennifer Menell
    16 Menell
  2. Wen-Jen Hwu
    28 Hwu
  3. Paul Chapman
    252 Chapman
  4. Katherine S Panageas
    331 Panageas
  5. Susan Krown
    87 Krown
  6. Alan N Houghton
    273 Houghton
  7. Carolyn J Quinn
    5 Quinn