Xeloda(capecitabine) for hrpc

Most commonly, taxotere is used alone (or with prednisone) as a 1st chemotherapy for hormone-refractory prostate cancer (See Tannock, IF, et al, NEJM 2004;351:1502-12. The FDA has approved taxotere given every 3 weeks based on the results of the Phase III trial documented in this paper. The question is, what can be added to taxotere to make it more effective (increase the response rate; increase survival) or to renew a response when taxotere as a single agent has failed? One such adder is high dose pulsed calcitriol; another is to add carboplatin; another might be to add estramustine phosphate. Stated another way, what combination of chemotherapies might HRPC patients use as 2nd, 3rd for 4th line chemotherapies? It is hoped that adding capecitabine, which acts synergistically with taxotere, might add to our list of available combinations.

While the papers referenced here are for mainly chemo-naive patients, I am hopeful that adding capecitabine to taxotere will again elicit a response in patients (including myself) who have previously used taxotere -- either singly or in other combinations. However, as far as I know there is no published data on this use in HRPC patients -- so patients and oncologists using this approach should do so with caution. My reasons for optimism are: capecitabine is a new chemo class different from taxanes; capecitabine might enhance the effect of taxotere or vice versa; the FDA has approved Xeloda/taxotere for metastatic breast cancer for patients who have failed Adriamycin® (doxorubicin).

Table 1. Xeloda(capecitabine) monotherapy or Taxotere (Docetaxel) in combination with Xeloda (capecitabine). Xeloda (capecitabine) is an oral pro-drug of 5-FU.

Reference	Phase and No. of Patients	Docetaxel	Xeloda (capecitabine)	PSA-RR(>50% decrease)	M-RR	MTP or MS
(1a)El-Rayes BF et al, Urology 2003	1, case report	-	2000mg/m2/day for 14 days of a 21 day cycle.	PSA undetectable at 6 mos.	Complete clinical response after 5 mos.
(1b)Morant R, et al., BJC 2004.	II, 25	-	1250 mg m(-2) orally twice daily on days 1-14 every 21 days. Based on toxicity data, they recommend a lower starting dose of 1000 mg x m2 orally twice daily.	3 (12%); response duration was 12, 17 and 32 weeks.	-	median time to tumour progression of all patients was 12 weeks
(2)Spicer J, et al, PCa Prostatic Dis. 2005	II, 14	-	1250 mg/m2 twice daily for two weeks of a three-week cycle.	1 of 14 patients experienced a partial response by both PSA and imaging of liver mets. 7 other patients had PSADT increased.	-	In 5/14 patients (36%) PSA stabilization was sustained beyond 18 wks, and in one patient to 24 wks.
(3)Kolodziej MA et al Clin Gen Cancer 2006	II, 77	60 mg/m2 every 21 days.	1000 mg/m2 BID days 1-14 each 21 day cycle; maximum of 8 cycles	41%	-	Median progression free survival 5.1 months; estimated one year survival 71%.
(4)Marur S., 2006 ASCO, abstract 4634	II, 21, chemo-naive.	36 mg/m2/week on days 1,8, and 15.	1250 mg/m2 /day in two divided doses on days 5-18.	14 of 18 patients (77%) with >90% PSA decline in 7 of 18 (39%) patients.	PR noted in 5 of 8 measurable disease patients. Stable disease by bone metastases in 15 of 18.	Median time to PSA progression was 5 months.
(5)Ferrero JM et al, Cancer 2006	II, 46, 13% had prior emcyt use.	35 mg /m2/week, 3 consecutive weeks.	625 mg/m2 twice daily (Days 5-18) every 28 days for 4 cycles.	30 of 44 assessable patients (68.2%), 14 of the 30(31.8%) normalized their PSA value.		The median overall survival time was 17.7 mos. (95% confidence interval, 15.8 mos. to not reached).

Note: The author is not a medical doctor and cannot render medical advice. As a prostate cancer patient, this was written in an attempt to understand these treatments and how it affects me. I make no claims that this review is definitive, complete or authoritative and I request any contributions to, or clarification of the subject which might contribute to the issue or inquiry. In conjunction with a medical team, every cancer patient must make their own decisions regarding treatment options. Your own medical team's directions should be carefully followed.

References

(6) Touffet S, Gayet G, Samperez S, Jouan P., Demonstration of thymidine phosphorylase activity in human healthy, adenomatous and cancerous prostate, Bull Cancer, 1992;79(2):151-9.

(7)Padma Nadella, Charles Shapiro, Gregory A. Otterson, Marsha Hauger, Selnur Erdal, Eric Kraut, Steven Clinton, Manisha Shah, Mike Stanek, Paul Monk, and Miguel A. Villalona-Calero, Pharmacobiologically Based Scheduling of Capecitabine and Docetaxel Results in Antitumor Activity in Resistant Human Malignancies, J. Clin. Oncol., Jun 1 2002: 2616–2623.

(8) Sawada N, Ishikawa T, Fukase Y, Nishida M, Yoshikubo T,

Ishitsuka H. Induction of thymidine phosphorylase activity and enhancement of capecitabine efficacy by taxol/taxotere in human cancer xenografts. Clin Cancer Res 1998;4:1013–9.

(9) Kurosumi M, Tabei T, Suemasu K, et al. Enhancement of immunohistochemical reactivity for thymidine phosphorylase in breast carcinoma cells after administration of docetaxel as a neoadjuvant chemotherapy in advanced breast cancer patients. Oncol Rep 2000;7:945– 8.

(8) R Leonard, J O'shaughnessy, S Vukelja, V Gorbounova, Ca Chan-Navarro, D Maraninchi, N Barak-Wigler, Jj McKendrick, Wg Harker, As Bexon, C Twelves, Detailed analysis of a randomized phase III trial: can the tolerability of capecitabine plus docetaxel be improved without compromising its survival advantage? Ann Oncol. 2006 Sep ;17:1379-85.

(9) Fischel JL, Ciccolini J, Formento P, Ferrero JM, Milano G., Synergistic cytotoxic interaction in hormone-refractory prostate cancer with the triple combination docetaxel-erlotinib and 5-fluoro-5'-deoxyuridine; Anticancer Drugs, 2006 Aug;17(7):807-13.