Skip to main content
SpringerLink
Log in

Evaluation of oral chemotherapy with capecitabine and cyclophosphamide plus thalidomide and prednisone in prostate cancer patients

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

The aim of this study was to evaluate clinical outcomes of second-line chemotherapy with capecitabine and cyclophosphamide (CTX) plus thalidomide and prednisone in refractory advanced castrate-resistant prostate cancer (CRPC) patients.

Methods

We retrospectively reviewed patients with advanced CRPC who had previously progressed to first-line docetaxel-based chemotherapy. Patients were given second-line chemotherapy with capecitabine and CTX plus thalidomide and prednisone throughout the course. Patients were evaluated for response and toxicity, and treatment was continued until the disease progression or excessive toxicity was noted.

Results

From April 2007 to February 2010, a total of 28 patients (median age, 72.8 ± 2.9 years) received second-line chemotherapy. The median cycle and duration of metronomic chemotherapy were six (range: 1–12) cycles and 6.3 (range 1.5–20.5) months, respectively. Prostatic-specific antigen was decreased by more than 50% in 10 (35.7%) of the 28 patients. All patients had bone metastases, and 8 patients (28.6%) had measurable soft tissue lesions. Among the 8 patients, 1 patient achieved partial response, and 3 patients had stabilized disease. With a median follow-up time of 29.5 (95% CI, 26.4–33.4) months, median composite progression-free survival and overall survival were 4.7 (95% CI, 3.4–5.7) months and 19.5 (95% CI, 18.9–25.5) months, respectively. No grade 3–4 toxicity was observed, and none of the patients experienced grade 3–4 hematological and nonhematological toxicities.

Conclusions

These data suggested that oral combination second-line chemotherapy with capecitabine and CTX plus thalidomide and prednisone offers promising activity with an excellent safety profile for patients with advanced CRPC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Beer TM, Ryan CW, Venner PM, Petrylak DP, Chatta GS, Ruether JD, Redfern CH, Fehrenbacher L, Saleh MN, Waterhouse DM, Carducci MA, Vicario D, Dreicer R, Higano CS, Ahmann FR, Chi KN, Henner WD, Arroyo A, Clow FW; ASCENT Investigators (2007) Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgen-independent prostate cancer: a report from the ASCENT Investigators. J Clin Oncol 5(6):669–674

  • Bertolini F, Paul S, Mancuso P, Monestiroli S, Gobbi A, Shaked Y, Kerbel RS (2003) Maximum tolerable dose and low-dose metronomic chemotherapy have opposite effects on the mobilization and viability of circulating endothelial progenitor cells. Cancer Res 63(15):4342–4346

    PubMed  CAS  Google Scholar 

  • Bocci G, Nicolaou KC, Kerbel RS (2002) Protracted low-dose effects on human endothelial cell proliferation and survival in vitro reveal a selective antiangiogenic window for various chemotherapeutic drugs. Cancer Res 62(23):6938–6943

    PubMed  CAS  Google Scholar 

  • Bocci G, Francia G, Man S, Lawler J, Kerbel RS (2003) Thrombospondin 1, a mediator of the antiangiogenic effects of low-dose metronomic chemotherapy. Proc Natl Acad Sci USA 100(22):12917–12922

    Article  PubMed  CAS  Google Scholar 

  • Bocci G, Tuccori M, Emmenegger U, Liguori V, Falcone A, Kerbel RS, Del Tacca M (2005) Cyclophosphamide- methotrexate ‘metronomic’ chemotherapy for the palliative treatment of metastatic breast cancer.A comparative pharmacoeconomic evaluation. Ann Oncol 16(8):1243–1252

    Article  PubMed  CAS  Google Scholar 

  • Budman DR, Meropol NJ, Reigner B, Creaven PJ, Lichtman SM, Berghorn E, Behr J, Gordon RJ, Osterwalder B, Griffin T (1998) Preliminary studies of a novel oral fluoropyrimidine carbamate: capecitabine. J Clin Oncol 16(5):1795–1802

    PubMed  CAS  Google Scholar 

  • De Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ, Goodman OB Jr, Saad F, Staffurth JN, Mainwaring P, Harland S, Flaig TW, Hutson TE, Cheng T, Patterson H, Hainsworth JD, Ryan CJ, Sternberg CN, Ellard SL, Fléchon A, Saleh M, Scholz M, Efstathiou E, Zivi A, Bianchini D, Loriot Y, Chieffo N, Kheoh T, Haqq CM, Scher HI; COU-AA-301 Investigators (2010) Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 26(21):1995–2005

    Google Scholar 

  • Dellapasqua S, Bertolini F, Bagnardi V, Campagnoli E, Scarano E, Torrisi R, Shaked Y, Mancuso P, Goldhirsch A, Rocca A, Pietri E, Colleoni M (2008) Metronomic cyclophosphamide and capecitabine combined with bevacizumab in advanced breast cancer. J Clin Oncol 26(30):4899–4905

    Article  PubMed  CAS  Google Scholar 

  • Di LG, Autorino R, De Laurentiis M, Forestieri V, Romano C, Prudente A, Giugliano F, Imbimbo C, Mirone V, De Placido S (2007) Thalidomide in combination with oral daily cyclophosphamide in patients with pretreated hormone refractory prostate cancer: a phase I clinical trial. Cancer Biol Ther 6(3):313–317

    Google Scholar 

  • El-Rayes BF, Black CA, Ensley JF (2003) Hormone-refractory prostate cancer responding to capecitabine. Urology 61(2):462

    Google Scholar 

  • Endo M, Shinbori N, Fukase Y, Sawada N, Ishikawa T, Ishitsuka H, Tanaka Y (1999) Induction of thymidine phosphorylase expression and enhancement of efficacy of capecitabine or 5′-deoxy-5-fluorouridine by cyclophosphamide in mammary tumor models. Int J Cancer 83(1):127–134

    Article  PubMed  CAS  Google Scholar 

  • Ferrero JM, Chamorey E, Oudard S, Dides S, Lesbats G, Cavaglione G, Nouyrigat P, Foa C, Kaphan R (2006) Phase II trial evaluating a docetaxel-capecitabine combination as treatment for hormone-refractory prostate cancer. Cancer 107(4):738–745

    Google Scholar 

  • Gasent BJM, Giner MV, Giner-Bosch V, Cerezuela FP, Alberola CV (2011) Phase II trial of oxaliplatin and capecitabine after progression to first-line chemotherapy in androgen-independent prostate cancer patients. Am J Clin Oncol 34(2):155–159

    Google Scholar 

  • Ghiringhelli F, Menard C, Puig PE, Ladoire S, Roux S, Martin F, Solary E, Le Cesne A, Zitvogel L, Chauffert B (2007) Metronomic cyclophosphamide regimen selectively depletes CD4+ CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol Immunother 56(5):641–648

    Article  PubMed  CAS  Google Scholar 

  • Gittes RF (1991) Carcinoma of the prostate. N Engl J Med 324(4):236–245

    Google Scholar 

  • Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60:277–300

    Article  PubMed  Google Scholar 

  • Kolodziej M, Neubauer MA, Rousey SR, Pluenneke RE, Perrine G, Mull S, Boehm KA, Ilegbodu D, Asmar L (2006) Phase II trial of docetaxel/capecitabine in hormone-refractory prostate cancer. Clin Genitourin Cancer 5(2):155–161

    Google Scholar 

  • Ma CG, Ye DW, Li CL, Zhou FJ, Yao XD, Zhang SL, Dai B, Zhang HL, Zhu Y, Shen YJ (2008) Epidemiology of prostate cancer from three centers and analysis of the first-line hormonal therapy for the advanced disease. Zhonghua Wai Ke Za Zhi 46(12):921–925

    PubMed  Google Scholar 

  • Miwa M, Ura M, Nishida M, Sawada N, Ishikawa T, Mori K, Shimma N, Umeda I, Ishitsuka H (1998) Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. Eur J Cancer 34(8):1274–1281

    Google Scholar 

  • Morant R, Bernhard J, Dietrich D, Gillessen S, Bonomo M, Borner M, Bauer J, Cerny T, Rochlitz C, Wernli M, Gschwend A, Hanselmann S, Hering F, Schmid HP (2004) Capecitabine in hormone-resistant metastatic prostatic carcinoma. Br J Cancer 90(7):1312–1317

    Article  PubMed  CAS  Google Scholar 

  • Payne SA (1992) A study of quality of life in cancer patients receiving palliative chemotherapy. Soc Sci Med 35(12):1505–1509

    Google Scholar 

  • Petrylak DP, Tangen CM, Hussain MH, Lara PN Jr, Jones JA, Taplin ME, Burch PA, Berry D, Moinpour C, Kohli M, Benson MC, Small EJ, Raghavan D, Crawford ED (2004) Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 351(15):1513–1520

    Article  PubMed  CAS  Google Scholar 

  • Pu YS (2000) Prostate cancer in Taiwan: epidemiology and risk factors. Int J Androl 23(Suppl 2):34–36

    Google Scholar 

  • Rodney A, Dieringer P, Mathew P, Jonasch E, Tannir N, Pagliaro LC (2006) Phase II study of capecitabine combined with gemcitabine in the treatment of androgen-independent prostate cancer previously treated with taxanes. Cancer 106(10):2143–2147

    Google Scholar 

  • Scher HI, Beer TM, Higano CS, Anand A, Taplin ME, Efstathiou E, Rathkopf D, Shelkey J, Yu EY, Alumkal J, Hung D, Hirmand M, Seely L, Morris MJ, Danila DC, Humm J, Larson S, Fleisher M, Sawyers CL; Prostate Cancer Foundation/Department of Defense Prostate Cancer Clinical Trials Consortium (2010) Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1-2 study. Lancet 375(9724):1437–1446

    Google Scholar 

  • Small EJ, Vogelzang NJ (1997) Second-line hormonal therapy for advanced prostate cancer: a shifting paradigm. J Clin Oncol 15(1):382–388

    PubMed  CAS  Google Scholar 

  • Spicer J, Plunkett T, Somaiah N, Chan S, Kendall A, Bolunwu N, Pandha H (2005) Phase II study of oral capecitabine in patients with hormone-refractory prostate cancer. Prostate Cancer Prostatic Dis 8(4):364–368

    Google Scholar 

  • Sternberg CN, Petrylak DP, Sartor O, Witjes JA, Demkow T, Ferrero JM, Eymard JC, Falcon S, Calabrò F, James N, Bodrogi I, Harper P, Wirth M, Berry W, Petrone ME, McKearn TJ, Noursalehi M, George M, Rozencweig M (2009) Multinational, double-blind, phase III study of prednisone and either satraplatin or placebo in patients with castrate-refractory prostate cancer progressing after prior chemotherapy: the SPARC trial. J Clin Oncol 27(32):5431–5438

    Google Scholar 

  • Tannock IF, Osoba D, Stockler MR, Ernst DS, Neville AJ, Moore MJ, Armitage GR, Wilson JJ, Venner PM, Coppin CM, Murphy KC (1996) Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points. J Clin Oncol 14(6):1756–1764

    Google Scholar 

  • Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, Théodore C, James ND, Turesson I, Rosenthal MA, Eisenberger MA, TAX 327 Investigators (2004) Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351(15):1502–1512

    Article  PubMed  CAS  Google Scholar 

  • Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate theresponse to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92(3):205–216

    Article  PubMed  CAS  Google Scholar 

  • Vaishampayan UN, Marur S, Heilbrun LK, Cher ML, Dickow B, Smith DW, Al Hasan SA, Eliason J (2009) Phase II trial of capecitabine and weekly docetaxel for metastatic castrate resistant prostate cancer. J Urol 182(1):317–323

    Google Scholar 

  • Yang PQ (2010) Overview of prostate cancer epidemiology. Chin J Med 45(10):875–877

    Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Hematology and Oncology, Jiangsu Province Geriatric Institute, 30 Luojia Road, Nanjing, Jiangsu, 210024, People’s Republic of China

    Li-Juan Meng, Jun Wang, Wei-Fei Fan, Xiao-Lin Pu, Fu-Yin Liu & Min Yang

Authors
  1. Li-Juan Meng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wei-Fei Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiao-Lin Pu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fu-Yin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Min Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jun Wang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Meng, LJ., Wang, J., Fan, WF. et al. Evaluation of oral chemotherapy with capecitabine and cyclophosphamide plus thalidomide and prednisone in prostate cancer patients. J Cancer Res Clin Oncol 138, 333–339 (2012). https://doi.org/10.1007/s00432-011-1101-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-011-1101-2

Keywords

Search

Navigation