Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma.

2.50
Hdl Handle:
http://hdl.handle.net/10541/86650
Title:
Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma.
Authors:
Middleton, Mark R; Grob, J J; Aaronson, N; Fierlbeck, G; Tilgen, W; Seiter, S; Gore, M; Aamdal, S; Cebon, J; Coates, A; Dreno, B; Henz, M; Schadendorf, D; Kapp, A; Weiss, J; Fraass, U; Statkevich, P; Muller, M; Thatcher, Nick
Abstract:
PURPOSE: To compare, in 305 patients with advanced metastatic melanoma, temozolomide and dacarbazine (DTIC) in terms of overall survival, progression-free survival (PFS), objective response, and safety, and to assess health-related quality of life (QOL) and pharmacokinetics of both drugs and their metabolite, 5-(3-methyltriazen-1-yl)imidazole-4-carboximide (MTIC). PATIENTS AND METHODS: Patients were randomized to receive either oral temozolomide at a starting dosage of 200 mg/m(2)/d for 5 days every 28 days or intravenous (IV) DTIC at a starting dosage of 250 mg/m(2)/d for 5 days every 21 days. RESULTS: In the intent-to-treat population, median survival time was 7.7 months for patients treated with temozolomide and 6.4 months for those treated with DTIC (hazards ratio, 1.18; 95% confidence interval [CI], 0.92 to 1.52). Median PFS time was significantly longer in the temozolomide-treated group (1.9 months) than in the DTIC-treated group (1.5 months) (P =.012; hazards ratio, 1.37; 95% CI, 1.07 to 1.75). No major difference in drug safety was observed. Temozolomide was well tolerated and produced a noncumulative, transient myelosuppression late in the 28-day cycle. The most common nonhematologic toxicities were mild to moderate nausea and vomiting, which were easily managed. Temozolomide therapy improved health-related QOL; more patients showed improvement or maintenance of physical functioning at week 12. Systemic exposure (area under the curve) to the parent drug and the active metabolite, MTIC, was higher after treatment with oral temozolomide than after IV administration of DTIC. CONCLUSION: Temozolomide demonstrates efficacy equal to that of DTIC and is an oral alternative for patients with advanced metastatic melanoma.
Affiliation:
Christie Hospital, Manchester, United Kingdom. mmiddleton@picr.man.ac.uk
Citation:
Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. 2000, 18 (1):158-66 J. Clin. Oncol.
Journal:
Journal of Clinical Oncology
Issue Date:
Jan-2000
URI:
http://hdl.handle.net/10541/86650
PubMed ID:
10623706
Type:
Article
Language:
en
ISSN:
0732-183X
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorMiddleton, Mark Ren
dc.contributor.authorGrob, J Jen
dc.contributor.authorAaronson, Nen
dc.contributor.authorFierlbeck, Gen
dc.contributor.authorTilgen, Wen
dc.contributor.authorSeiter, Sen
dc.contributor.authorGore, Men
dc.contributor.authorAamdal, Sen
dc.contributor.authorCebon, Jen
dc.contributor.authorCoates, Aen
dc.contributor.authorDreno, Ben
dc.contributor.authorHenz, Men
dc.contributor.authorSchadendorf, Den
dc.contributor.authorKapp, Aen
dc.contributor.authorWeiss, Jen
dc.contributor.authorFraass, Uen
dc.contributor.authorStatkevich, Pen
dc.contributor.authorMuller, Men
dc.contributor.authorThatcher, Nicken
dc.date.accessioned2009-11-23T10:21:06Z-
dc.date.available2009-11-23T10:21:06Z-
dc.date.issued2000-01-
dc.identifier.citationRandomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. 2000, 18 (1):158-66 J. Clin. Oncol.en
dc.identifier.issn0732-183X-
dc.identifier.pmid10623706-
dc.identifier.urihttp://hdl.handle.net/10541/86650-
dc.description.abstractPURPOSE: To compare, in 305 patients with advanced metastatic melanoma, temozolomide and dacarbazine (DTIC) in terms of overall survival, progression-free survival (PFS), objective response, and safety, and to assess health-related quality of life (QOL) and pharmacokinetics of both drugs and their metabolite, 5-(3-methyltriazen-1-yl)imidazole-4-carboximide (MTIC). PATIENTS AND METHODS: Patients were randomized to receive either oral temozolomide at a starting dosage of 200 mg/m(2)/d for 5 days every 28 days or intravenous (IV) DTIC at a starting dosage of 250 mg/m(2)/d for 5 days every 21 days. RESULTS: In the intent-to-treat population, median survival time was 7.7 months for patients treated with temozolomide and 6.4 months for those treated with DTIC (hazards ratio, 1.18; 95% confidence interval [CI], 0.92 to 1.52). Median PFS time was significantly longer in the temozolomide-treated group (1.9 months) than in the DTIC-treated group (1.5 months) (P =.012; hazards ratio, 1.37; 95% CI, 1.07 to 1.75). No major difference in drug safety was observed. Temozolomide was well tolerated and produced a noncumulative, transient myelosuppression late in the 28-day cycle. The most common nonhematologic toxicities were mild to moderate nausea and vomiting, which were easily managed. Temozolomide therapy improved health-related QOL; more patients showed improvement or maintenance of physical functioning at week 12. Systemic exposure (area under the curve) to the parent drug and the active metabolite, MTIC, was higher after treatment with oral temozolomide than after IV administration of DTIC. CONCLUSION: Temozolomide demonstrates efficacy equal to that of DTIC and is an oral alternative for patients with advanced metastatic melanoma.en
dc.language.isoenen
dc.subjectCancer Metastasisen
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAged, 80 and over-
dc.subject.meshAntineoplastic Agents, Alkylating-
dc.subject.meshBiological Availability-
dc.subject.meshConsumer Product Safety-
dc.subject.meshDacarbazine-
dc.subject.meshDisease-Free Survival-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshMale-
dc.subject.meshMelanoma-
dc.subject.meshNeoplasm Metastasis-
dc.subject.meshQuality of Life-
dc.subject.meshRegression Analysis-
dc.subject.meshSurvival Rate-
dc.titleRandomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma.en
dc.typeArticleen
dc.contributor.departmentChristie Hospital, Manchester, United Kingdom. mmiddleton@picr.man.ac.uken
dc.identifier.journalJournal of Clinical Oncologyen

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