Phase I study of weekly (day 1 and 8) docetaxel in combination with capecitabine in patients with advanced solid malignancies.
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.
Ramanathan
Ramesh K
RK
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.
Ramalingam
Sakkaraiappan
S
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.
Egorin
Merrill J
MJ
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.
Belani
Chandra P
CP
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.
Potter
Douglas M
DM
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.
Fakih
Marwan
M
Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Jung
Laura L
LL
Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA.
Strychor
Sandra
S
Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA.
Jacobs
Samuel A
SA
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.
Friedland
David M
DM
Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Shin
Dong M
DM
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.
Chatta
Gurkamal S
GS
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.
Tutchko
Susan
S
Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA.
Zamboni
William C
WC
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.
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
D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000069287:Capecitabine; D005472:Fluorouracil