title: Phase I study of the combination of docetaxel, temozolomide and cisplatin in patients with metastatic melanoma.
abstract: OBJECTIVE
  In a search for more effective combination chemotherapy for the treatment of metastatic melanoma, we conducted a phase I trial of a novel combination of docetaxel, temozolomide, and cisplatin.
  
  
  METHODS
  Patients with inoperable or recurrent metastatic melanoma with a Zubrod performance status of 2 or less and adequate organ function were eligible. The dose of docetaxel was escalated between cohorts of patients, and the doses of temozolomide and cisplatin were fixed. A standard 3 + 3 dose escalation design was used to determine the maximum tolerated dose (MTD).
  
  
  RESULTS
  Among 23 patients who were enrolled, 21 were evaluable for toxicity. Eighteen patients (78%) had stage IV-M1c disease. The dose-limiting toxicities were myelosuppression and pulmonary embolism. The MTD was 30 mg/m(2) docetaxel on days 1, 8, and 15 when given with 150 mg/m(2) temozolomide on days 1-5, and 20 mg/m(2) cisplatin on days 1-4, repeating every 4 weeks. Among 19 patients evaluated for response, 6 (32%) had partial responses and 5 (26%) had stable disease. Among 14 chemo-naive patients, 6 (43%) had a partial response and 4 (29%) had stable disease. Nine patients developed brain metastases by the time of the last follow-up evaluation, and the median time to brain metastases for all 19 evaluable patients has not been reached.
  
  
  CONCLUSIONS
  This combination was well tolerated and appears to be a promising treatment for patient with metastatic melanoma.
authors.affiliation: Department of Melanoma Medical Oncology, Unit 430, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. kkim@mdanderson.org
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Kim
authors.forename: Wen-Jen
authors.initials: WJ
authors.lastname: Hwu
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Papadopoulos
authors.forename: Agop Y
authors.initials: AY
authors.lastname: Bedikian
authors.forename: Luis H
authors.initials: LH
authors.lastname: Camacho
authors.forename: Chaan
authors.initials: C
authors.lastname: Ng
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: Hernandez
authors.forename: Angela M
authors.initials: AM
authors.lastname: Frost
authors.forename: Monica A
authors.initials: MA
authors.lastname: Jack
authors.forename: Patrick
authors.initials: P
authors.lastname: Hwu
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001932:Brain Neoplasms / Q000556:secondary; D002945:Cisplatin / Q000008:administration & dosage; D015331:Cohort Studies; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced*; D011655:Pulmonary Embolism / Q000139:chemically induced; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D003606:Dacarbazine; D002945:Cisplatin; D000077204:Temozolomide