title: Phase I study of weekly (day 1 and 8) docetaxel in combination with capecitabine in patients with advanced solid malignancies.
abstract: OBJECTIVE
  Capecitabine in combination with docetaxel given every 3 weeks has shown a high degree of activity in a number of tumor types, but at the expense of significant toxicity. To improve the therapeutic index, we evaluated a weekly regimen of docetaxel in combination with capecitabine, and determined the maximum tolerated dose, toxicities and pharmacokinetics of this combination.
  
  
  METHODS
  Patients with advanced solid malignancies were treated with docetaxel on days 1 and 8, and capecitabine, twice daily on days 1-14, of an every-21-day cycle. Pharmacokinetics of docetaxel were assessed on days 1 and 8 of the first cycle of chemotherapy.
  
  
  RESULTS
  Enrolled in the study were 25 patients. The most frequent toxicities were asthenia, hand-foot syndrome and mucositis. Inability to deliver at least 75% of the planned doses of both drugs during the first two cycles of chemotherapy was noted at dose levels 2, 3 and 4. Dose level 1 (docetaxel 30 mg/m2 and capecitabine 825 mg/m2 twice daily) is the recommended dose for phase II studies. Five patients experienced a partial response, and eight patients had stabilization of disease. Coadministration of capecitabine did not alter the pharmacokinetics of docetaxel.
  
  
  CONCLUSIONS
  The regimen consisting of docetaxel 30 mg/m2 (days 1, 8) and capecitabine 825 mg/m2 twice daily (days 1-14) was well tolerated. Capecitabine did not alter pharmacokinetics of docetaxel. Further testing of this regimen in tumor-specific trials, especially gastric, lung and breast cancer, is warranted.
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. ramanathanrk@upmc.edu.|Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA. ramanathanrk@upmc.edu.
authors.forename: Ramesh K
authors.initials: RK
authors.lastname: Ramanathan
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.|Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA.
authors.forename: Sakkaraiappan
authors.initials: S
authors.lastname: Ramalingam
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.|Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA.
authors.forename: Merrill J
authors.initials: MJ
authors.lastname: Egorin
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.|Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA.
authors.forename: Chandra P
authors.initials: CP
authors.lastname: Belani
authors.affiliation: Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA.|Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Potter
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Marwan
authors.initials: M
authors.lastname: Fakih
authors.affiliation: Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Jung
authors.affiliation: Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Strychor
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.|Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA.
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Jacobs
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Friedland
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.|Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA.
authors.forename: Dong M
authors.initials: DM
authors.lastname: Shin
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.|Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA.
authors.forename: Gurkamal S
authors.initials: GS
authors.lastname: Chatta
authors.affiliation: Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Tutchko
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.|Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA.|Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Zamboni
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001247:Asthenia / Q000139:chemically induced*; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000077143:Docetaxel; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009092:Mucous Membrane / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy*; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000069287:Capecitabine; D005472:Fluorouracil