title: Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  Temozolomide demonstrates efficacy equal to that of DTIC and is an oral alternative for patients with advanced metastatic melanoma.
authors.affiliation: Christie Hospital, Manchester, United Kingdom. mmiddleton@picr.man.ac.uk
authors.forename: M R
authors.initials: MR
authors.lastname: Middleton
authors.forename: J J
authors.initials: JJ
authors.lastname: Grob
authors.forename: N
authors.initials: N
authors.lastname: Aaronson
authors.forename: G
authors.initials: G
authors.lastname: Fierlbeck
authors.forename: W
authors.initials: W
authors.lastname: Tilgen
authors.forename: S
authors.initials: S
authors.lastname: Seiter
authors.forename: M
authors.initials: M
authors.lastname: Gore
authors.forename: S
authors.initials: S
authors.lastname: Aamdal
authors.forename: J
authors.initials: J
authors.lastname: Cebon
authors.forename: A
authors.initials: A
authors.lastname: Coates
authors.forename: B
authors.initials: B
authors.lastname: Dreno
authors.forename: M
authors.initials: M
authors.lastname: Henz
authors.forename: D
authors.initials: D
authors.lastname: Schadendorf
authors.forename: A
authors.initials: A
authors.lastname: Kapp
authors.forename: J
authors.initials: J
authors.lastname: Weiss
authors.forename: U
authors.initials: U
authors.lastname: Fraass
authors.forename: P
authors.initials: P
authors.lastname: Statkevich
authors.forename: M
authors.initials: M
authors.lastname: Muller
authors.forename: N
authors.initials: N
authors.lastname: Thatcher
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001682:Biological Availability; D003257:Consumer Product Safety; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009362:Neoplasm Metastasis; D011788:Quality of Life; D012044:Regression Analysis; D015996:Survival Rate
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine