title: Phase I trial of weekly docetaxel and daily temozolomide in patients with metastatic disease.
abstract: Docetaxel is second generation taxoid that has shown activity against a variety of cancers and has been approved for use in cancers of the breast, lung, head and neck, ovaries and prostate. Temozolomide is an alkylating agent which crosses the blood brain barrier and has demonstrated antitumor activity against a broad range of tumor types, including malignant glioma, melanoma, non small cell lung cancer and carcinoma of the ovary and colon. A Phase I trial was conducted to determine the toxicity of this combination in refractory solid tumor patients.
  
  
  METHODS
  Twenty five patients with metastatic cancers were enrolled in a Phase I dose escalation trial. Docetaxel was administered weekly in 5 escalating doses of 25 to 35 mg/ m(2) as a one-hour bolus intravenous infusion for 3 consecutive weeks. Temozolamide was administered orally daily for 3 weeks (escalating doses of 75 to 100 mg/m(2)). Cycles were repeated at 4 week intervals.
  
  
  RESULTS
  The maximum tolerated dose (MTD) was not determined in this study. The most commonly reported adverse events were mild to moderate nausea, vomiting and fatigue. Thrombocytopenia was the most commonly observed grade 3 and 4 hematological toxicity. Eight patients had dose interruptions for adverse events and only one patient had a dose reduction while receiving 30 mg/ m(2) of docetaxel and 90 mg/ m(2) of temozolomide due to grade 3 thrombocytopenia. Two patients achieved partial responses and 88% of the patients are deceased. The median survival is 8.4 months.
  
  
  CONCLUSIONS
  The combination of docetaxel and temozolomide was well tolerated and these agents can be safely combined. For phase II trials, docetaxel 35 mg/ m(2) IV day 1, 8 and 15, and daily temozolomide at 100 mg/ m(2) day 1-21 are recommended.
authors.affiliation: Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Center, Cleveland, OH 44195, USA. tamaski@ccf.org
authors.forename: I
authors.initials: I
authors.lastname: Tamaskar
authors.forename: T
authors.initials: T
authors.lastname: Mekhail
authors.forename: R
authors.initials: R
authors.lastname: Dreicer
authors.forename: T
authors.initials: T
authors.lastname: Olencki
authors.forename: S
authors.initials: S
authors.lastname: Roman
authors.forename: P
authors.initials: P
authors.lastname: Elson
authors.forename: R M
authors.initials: RM
authors.lastname: Bukowski
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy*; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D000077204:Temozolomide
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D003606:Dacarbazine; D000077204:Temozolomide