Phase II trial of capecitabine and weekly docetaxel for metastatic castrate resistant prostate cancer.
OBJECTIVE
Synergy is observed with the combination of capecitabine and docetaxel due to docetaxel mediated up-regulation of thymidine phosphorylase. A phase II trial was performed with the combination for metastatic, castrate resistant prostate cancer.


METHODS
Eligible patients had metastatic, castrate resistant prostate cancer, no prior chemotherapy for metastatic disease and normal organ function. Docetaxel (36 mg/m(2) per week intravenously) on days 1, 8 and 15, and capecitabine (1,250 mg/m(2) per day in 2 divided doses) on days 5 to 18 were administered in 28-day cycles. The response was assessed every 2 cycles. Biomarker correlative studies were performed on blood dihydropyrimidine dehydrogenase, and the thymidine phosphorylase-to-dihydropyrimidine dehydrogenase and thymidine synthase-to-dihydropyrimidine dehydrogenase ratios in available prostate tumor tissue.


RESULTS
A total of 30 patients with a median age of 69 years were enrolled in the study. We noted bone pain in 21 patients (70%), Gleason score 8 or higher in 18 (60%), measurable disease progression in 9, bone scan progression in 18 and prostate specific antigen progression in 22. Grade 3 or 4 neutropenia was seen in 3 patients and grade 3 hand-foot syndrome was found in 2. No treatment related deaths occurred. A prostate specific antigen response of 50% or greater decrease was observed in 22 patients (73%), of whom 9 (30%) had 90% or greater decrease. A partial response was noted in 5 of 9 patients (56%) with measurable disease. Median time to progression was 6.7 months (90% CI 4.2-7.7) and median overall survival was 22.0 months (90% CI 18.4-25.3).


CONCLUSIONS
The combination was well tolerated and it demonstrated favorable response rates with durable remission and survival outcomes.
Vaishampayan
Ulka N
UN
Division of Oncology, Department of Internal Medicine, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, USA. vaishamu@karmanos.org
Marur
Shanthi
S
Heilbrun
Lance K
LK
Cher
Michael L
ML
Dickow
Brenda
B
Smith
Daryn W
DW
Al Hasan
Samir A
SA
Eliason
James
J
D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000069287:Capecitabine; D016001:Confidence Intervals; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D011336:Probability; D011379:Prognosis; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D017211:Treatment Failure; D016896:Treatment Outcome
D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000069287:Capecitabine; D005472:Fluorouracil