Capecitabine in hormone-resistant metastatic prostatic carcinoma – a phase II trial

Abstract

The objective of the trial is to evaluate the efficacy of capecitabine in patients with metastatic hormone-resistant prostate carcinoma (HRPC), in terms of prostate-specific antigen (PSA) response and clinical benefit (decrease of pain or analgesic score) and its safety profile. In all, 25 patients with HRPC were enrolled on a phase II trial of capecitabine (Xeloda s ) at a dose of 1250 mg m À2 orally twice daily on days 1 -14 every 21 days. The inclusion criteria were PSA serum levels 43 Â upper limit of normal, a WHO performance status 0 -2, age o85 years and adequate bone marrow, liver and renal function. In patients with grade 2 or higher haematological toxicity on day 1 of the treatment cycle, therapy was first delayed, and then continued at a lower dose. Trial end points were PSA response and clinical benefit defined by quality of life (QL) data and analgesic consumption. The median age of patients was 70 years (range 54 -85 years). A median of three cycles of capecitabine was administered (range 1 -8). PSA response was observed in three patients (12%, 95% CI 3 -31%), with times to tumour progression of 18, 21 and 35 weeks, respectively. In these patients, the response durations were 12, 17 and 32 weeks, respectively. Minor PSA regression was also seen in two further patients. The median time to tumour progression of all patients was 12 weeks (95% CI 9 -15 weeks). Haematological toxicity was minor, with leukopenia grade 3 observed in one patient. There were three deaths during trial treatment, respectively, due to sepsis following mucositis and leukopenia, presumed sepsis with mucositis induced by chemotherapy and concomitant radiotherapy and cerebral dysfunction progressing to coma. Hand -foot syndrome grades 2 and 3 were observed in four patients each. Clinical benefit was observed in five patients (20%, CI 7 -41%). Based on toxicity data, we recommend a lower starting dose of 1000 mg m À2 orally twice daily. While capecitabine has some activity in HRPC, as suggested by observed PSA responses, we conclude that it is not worthwhile to investigate capecitabine monotherapy in a phase III trial. Combinations of capecitabine with other agents, such as vinorelbine or docetaxel, may prove to be more effective.

Low‐dose docetaxel enhances the sensitivity of S‐1 in a xenograft model of human castration resistant prostate cancer

“…36 Additionally, capecitabine, an oral fluoropyrimidine, is an interesting example that can be considered when discussing combination therapy involving docetaxel and fluoropyrimidine. Although capecitabine monotherapy showed only limited activity in CRPC patients (PSA response rate was 12%) 37 , the combination of weekly docetaxel (35-36 mg/m 2 ) and capecitabine yielded extremely high PSA response rates of 73 and 68.2% in 2 phase II clinical trials. 38,39 Although direct comparisons are not feasible, these response rates were better than those in the TAX327 study (45 and 48%).…”

Phase II study of capecitabine combined with gemcitabine in the treatment of androgen‐independent prostate cancer previously treated with taxanes

“…5 The final step in the conversion is mediated by thymidine phosphorylase, an enzyme that is abundant in prostate tumor tissue. 7 The response rates of AIPCa to singleagent 5-FU, capecitabine, or gemcitabine chemotherapy are only reported to be 7% to 12%, [7][8][9][10][11][12] but to our knowledge, the effect of combining these agents is not known. We evaluated the efficacy, safety, and tolerability of gemcitabine and capecitabine as salvage therapy for AIPCa patients who were previously treated with taxanes in a single-center, Phase II clinical trial.…”

Phase II study of oral capecitabine in patients with hormone-refractory prostate cancer

“…Toxicity was significant but manageable, and compares favourably with that of standard palliative chemotherapy regimens used in advanced prostate cancer. Experience with capecitabine in prostate cancer in Switzerland was associated with more severe toxicity, 26 including two treatment-related deaths, a distinction possibly accounted for by pharmacogenomic differences in the study populations. We observed acceptable levels of toxicity, and indications of efficacy suggest that further studies are required to evaluate the role of capecitabine in this disease.…”