Randomized phase II study of temozolomide given every 8 hours or daily with either interferon alfa-2b or thalidomide in metastatic malignant melanoma.

2.50
Hdl Handle:
http://hdl.handle.net/10541/78176
Title:
Randomized phase II study of temozolomide given every 8 hours or daily with either interferon alfa-2b or thalidomide in metastatic malignant melanoma.
Authors:
Danson, Sarah; Lorigan, Paul C ( 0000-0002-8875-2164 ) ; Arance, Ana; Clamp, Andrew R; Ranson, Malcolm R; Hodgetts, Jackie; Lomax, Lyn; Ashcroft, Linda; Thatcher, Nick; Middleton, Mark R
Abstract:
PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: Of the three regimens tested, the combination of temozolomide and thalidomide seems the most promising for future study.
Affiliation:
Christie Hospital, Manchester, United Kingdom. sdanson@fsmail.net
Citation:
Randomized phase II study of temozolomide given every 8 hours or daily with either interferon alfa-2b or thalidomide in metastatic malignant melanoma. 2003, 21 (13):2551-7 J. Clin. Oncol.
Journal:
Journal of Clinical Oncology
Issue Date:
1-Jul-2003
URI:
http://hdl.handle.net/10541/78176
DOI:
10.1200/JCO.2003.10.039
PubMed ID:
12829675
Type:
Article
Language:
en
ISSN:
0732-183X
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorDanson, Sarah-
dc.contributor.authorLorigan, Paul C-
dc.contributor.authorArance, Ana-
dc.contributor.authorClamp, Andrew R-
dc.contributor.authorRanson, Malcolm R-
dc.contributor.authorHodgetts, Jackie-
dc.contributor.authorLomax, Lyn-
dc.contributor.authorAshcroft, Linda-
dc.contributor.authorThatcher, Nick-
dc.contributor.authorMiddleton, Mark R-
dc.date.accessioned2009-08-21T11:49:32Z-
dc.date.available2009-08-21T11:49:32Z-
dc.date.issued2003-07-01-
dc.identifier.citationRandomized phase II study of temozolomide given every 8 hours or daily with either interferon alfa-2b or thalidomide in metastatic malignant melanoma. 2003, 21 (13):2551-7 J. Clin. Oncol.en
dc.identifier.issn0732-183X-
dc.identifier.pmid12829675-
dc.identifier.doi10.1200/JCO.2003.10.039-
dc.identifier.urihttp://hdl.handle.net/10541/78176-
dc.description.abstractPURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: Of the three regimens tested, the combination of temozolomide and thalidomide seems the most promising for future study.en
dc.language.isoenen
dc.subjectSkin Canceren
dc.subjectCancer Metastasisen
dc.subject.meshAdolescent-
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAged, 80 and over-
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols-
dc.subject.meshDacarbazine-
dc.subject.meshDisease Progression-
dc.subject.meshDrug Administration Schedule-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshInfusions, Intravenous-
dc.subject.meshInjections, Subcutaneous-
dc.subject.meshInterferon Alfa-2b-
dc.subject.meshMale-
dc.subject.meshMelanoma-
dc.subject.meshMiddle Aged-
dc.subject.meshNeoplasm Metastasis-
dc.subject.meshSkin Neoplasms-
dc.subject.meshSurvival-
dc.subject.meshThalidomide-
dc.titleRandomized phase II study of temozolomide given every 8 hours or daily with either interferon alfa-2b or thalidomide in metastatic malignant melanoma.en
dc.typeArticleen
dc.contributor.departmentChristie Hospital, Manchester, United Kingdom. sdanson@fsmail.neten
dc.identifier.journalJournal of Clinical Oncologyen

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