Randomized Phase II Study of Temozolomide Given Every 8 Hours or Daily With Either Interferon Alfa-2b or Thalidomide in Metastatic Malignant Melanoma

• Published in: Journal of clinical oncology Vol. 21; no. 13; pp. 2551 - 2557
• Main Authors: DANSON, S, LORIGAN, P, ARANCE, A, CLAMP, A, RANSON, M, HODGETTS, J, LOMAX, L, ASHCROFT, L, THATCHER, N, MIDDLETON, M. R
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 01-07-2003; Lippincott Williams & Wilkins
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Combined treatments (chemotherapy of immunotherapy associated with an other treatment); Dacarbazine - administration & dosage; Dacarbazine - analogs & derivatives; Disease Progression; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Injections, Subcutaneous; Interferon-alpha - administration & dosage; Male; Medical sciences; Melanoma - drug therapy; Melanoma - pathology; Middle Aged; Neoplasm Metastasis; Pharmacology. Drug treatments; Recombinant Proteins; Skin Neoplasms - drug therapy; Skin Neoplasms - pathology; Survival; Thalidomide - administration & dosage; Antineoplastic agent; Skin disease; Biological response modifier; Prognosis; Toxicity; Administration schedule; Immunotherapy; Phase II trial; Complication; Advanced stage; Subcutaneous administration; Antiangiogenic agent; Thalidomide; Human; Drug combination; Treatment efficiency; Cytokine; Melanoma; Oral administration; Malignant tumor; Alkylating agent; Chemotherapy; Interferon alpha 2b; Combined treatment; Temozolomide
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2003.10.039

Temozolomide is an imidazotetrazine with a mechanism of action similar to dacarbazine and equivalent activity in melanoma. It is well tolerated and is a candidate for combination chemotherapy and schedule manipulation. In this study, we combined temozolomide with interferon alfa-2b and, separately, with thalidomide, and we administered temozolomide alone in a compressed schedule. The objectives of this randomized phase II, two-center study were to determine response rates, overall survival, and tolerability of the regimens in patients with advanced metastatic melanoma.
One hundred eighty-one patients with metastatic melanoma were randomly assigned to receive up to six 4-weekly cycles consisting of temozolomide 200 mg/m2 every 8 hours for five doses, or temozolomide 200 mg/m2 daily for days 1 to 5 plus interferon alfa-2b 5 MU (million International Units) subcutaneously three times a week, or temozolomide 150 mg/m2 (increased after one cycle to 200 mg/m2) daily on days 1 to 5 plus thalidomide 100 mg daily days 1 to 28.
The treatment arms were well balanced for known prognostic factors. Median survival was 5.3 months for 8-hourly temozolomide, 7.7 months for temozolomide/interferon, and 7.3 months for temozolomide/thalidomide; and 1-year survivals were 18%, 26%, and 24%, respectively. Response or disease stabilization occurred in 20% of patients (95% confidence interval [CI], 10% to 33%) given 8-hourly temozolomide, 21% (95% CI, 12% to 33%) given temozolomide/interferon, and 25% (95% CI, 15% to 38%) given temozolomide/thalidomide. Grade 3 or 4 nonhematologic toxicities were similar in each arm except for infection, which was more frequent with 8-hourly temozolomide. There were fewer instances of grade 3 or 4 myelotoxicity with temozolomide/thalidomide.
Of the three regimens tested, the combination of temozolomide and thalidomide seems the most promising for future study.