Skip to main content

Advertisement

SpringerLink
Log in

Metronomic chemotherapy with cyclophosphamide plus low dose of corticosteroids in advanced castration-resistant prostate cancer across the era of taxanes and new hormonal drugs

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

The aim of our study is to investigate the efficacy of metronomic cyclophosphamide plus low dose of corticosteroids in advanced or metastatic castration-resistant prostate cancer (CRPC) before, between, and after standard chemotherapy, such as docetaxel and cabazitaxel, and new hormonal treatments, such as abiraterone and enzalutamide. A retrospective analysis was performed on 37 patients. Cyclophosphamide was given orally 50 mg per day together with low dose of corticosteroids, namely dexametasone orally 1 mg per day or prednisone 10 mg per day. Seventeen patients (51%) showed a PSA decline≥ 50%. Median progression-free survival (PFS) and overall survival (OS) were 11 and 28 months, respectively. Median PFS and OS in the subgroup of patients with a PSA decline ≥ 50% were 14 and 35 months, respectively. Treatment was very well tolerated. We suggest that oral metronomic cyclophosphamide plus low dose of oral dexamethasone or prednisone may be a good and safe therapeutic option not only in those CRPC patients unfit for standard treatments but also in those heavily pre-treated patients.

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

Similar content being viewed by others

References

  1. Kerbel RS, Kamen BA. The anti-angiogenic basis of metronomic chemotherapy. Nat Rev Cancer. 2004;4:423–36.

    Article  CAS  Google Scholar 

  2. Orlando L, Cardillo A, Rocca A, Balduzzi A, Ghisini R, Peruzzotti G, Goldhirsch A, D’Alessandro C, Cinieri S, Preda L, Colleoni M. Prolonged clinical benefit with metronomic chemotherapy in patients with metastatic breast cancer. Anticancer Drugs. 2006;17:961–7.

    Article  CAS  Google Scholar 

  3. Mancuso P, Colleoni M, Calleri A, Orlando L, Maisonneuve P, Pruneri G, Agliano A, Goldhirsch A, Shaked Y, Kerbel RS, Bertolini F. Circulating endothelial-cell kinetics and viability predict survival in breast cancer patients receiving metronomic chemotherapy. Blood. 2006;108:452–9.

    Article  CAS  Google Scholar 

  4. Calvani N, Orlando L, Nacci A, Sponziello F, Cinefra M, Cinieri S. Metronomic chemotherapy against cancer: from paradigm to clinical practice? Tumori. 2009;95:843–5.

    Article  CAS  Google Scholar 

  5. Lien K, Georgsdottir S, Sivanathan L, Chan K, Emmenegger U. Low-dose metronomic chemotherapy: a systematic literature analysis. Eur J Cancer. 2013;49:3387–95.

    Article  CAS  Google Scholar 

  6. Glode LM, Barqawi A, Crighton F, Crawford ED, Kerbel R. Metronomic therapy with cyclophosphamide and dexamethasone for prostate carcinoma. Cancer. 2003;98:1643–8.

    Article  CAS  Google Scholar 

  7. Nicolini A, Mancini P, Ferrari P, Anselmi L, Tartarelli G, Bonazzi V, Carpi A, Giardino R. Oral low-dose cyclophosphamide in metastatic hormone refractory prostate cancer (MHRPC). Biomed Pharmacother. 2004;58:447–50.

    Article  CAS  Google Scholar 

  8. Lord R, Nair S, Schache A, Spicer J, Somaihah N, Khoo V, Pandha H. Low dose metronomic oral cyclophosphamide for hormone resistant prostate cancer: a phase II study. J Urol. 2007;177:2136–41.

    Article  CAS  Google Scholar 

  9. Nelius T, Klatte T, de Riese W, Haynes A, Filleur S. Clinical outcome of patients with docetaxel-resistant hormone-refractory prostate cancer treated with second-line cyclophosphamide-based metronomic chemotherapy. Med Oncol. 2010;27:363–7.

    Article  CAS  Google Scholar 

  10. Nelius T, Rinard K, Filleur S. Oral/metronomic cyclophosphamide-based chemotherapy as option for patients with castration-refractory prostate cancer: review of the literature. Cancer Treat Rev. 2011;37:444–55.

    Article  CAS  Google Scholar 

  11. Yashi M, Nishihara D, Mizuno T, Yuki H, Masuda A, Kambara T, Betsunoh H, Abe H, Fukabori Y, Muraishi O, Kamai T. Metronomic oral cyclophosphamide chemotherapy possibly contributes to stabilization of disease in patients with metastatic castration-resistant prostate cancer: a prospective analysis of consecutive cases. Clin Genitourin Cancer. 2014;12:197–203.

    Article  Google Scholar 

  12. Ladoire S, Eymard JC, Zanetta S, Mignot G, Martin E, Kermarrec I, Mourey E, Michel F, Cormier L, Ghiringhelli F. Metronomic oral cyclophosphamide prednisolone chemotherapy is an effective treatment for metastatic hormone-refractory prostate cancer after docetaxel failure. Anticancer Res. 2010;30:4317–24.

    CAS  PubMed  Google Scholar 

  13. Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1990;82:4–6.

    Article  CAS  Google Scholar 

  14. Broweder T, Butterfield CE, Kraling MT, Marshall B, O’Reilly MS, Folkman J. Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. Cancer Res. 2000;60:1878–86.

    Google Scholar 

  15. Chow A, Wong A, Francia G, Man S, Kerbel RS, Emmenegger U. Preclinical analysisi of resistance and cross-resistance to low-dose metronomic chemotherapy. Invest New Drugs. 2014;32:47–59.

    Article  CAS  Google Scholar 

  16. Fontana A, Galli L, Fioravanti A, Orlandi P, Galli C, Landi L, Bursi S, Allegrini G, Fontana E, Di Marsico R, Antonuzzo A, D’Arcangelo M, Danesi R, Del Tacca M, Falcone A, Bocci G. Clinical and pharmacodynamic evaluation of metronomic cyclophosphamide, celecoxib, and dexamethasone in advanced hormone-refractory prostate cancer. Clin Cancer Res. 2009;15:4954–62.

    Article  CAS  Google Scholar 

  17. Rozados VR, Mainetti LE, Rico MJ, Zacarias Fluck MF, Matar P, Scharovsky OG. The immune response and the therapeutic effect of metronomic chemotherapy with cyclophosphamide. Oncol Res. 2010;18:601–5.

    Article  Google Scholar 

  18. Ghiringhelli F, Menard C, Puig PE, Ladoire S, Roux S, Martin F, Solary E, Le Cesne A, Zitvogel L, Chauffert B. Metronomic cyclophosphamide regimen selectively depletes CD4 + CD25 + regulatory T cells and restores T and NK effector functions in end stage cancer patient. Cancer Immunol Immunother. 2006;56:641–8.

    Article  Google Scholar 

  19. Wada S, Yoshimura K, Hipkiss EL, Harris TJ, Yen H, Goldberg MV, Grosso JF, Getnet D, Demarzo AM, Netto GJ, Anders R, Pardoll DM, Drake CG. Cyclophosphamide augments antitumor immunity: studies in autochthonous prostate cancer model. Cancer Res. 2009;69:4309–18.

    Article  CAS  Google Scholar 

  20. Venkitaraman R, Lorente D, Murthy V, Thomas K, Parker L, Ahiabor R, Dearnaley D, Huddart R, De Bono J, Parker C. A randomised phase 2 trial of dexamethasone versus prednisolone in castration-resistant prostate cancer. Eur Urol. 2015;67:673–9.

    Article  CAS  Google Scholar 

  21. Morioka M, Kobayashi T, Furukawa Y, Jo Y, Shinkai M, Matsuki T, Yamamoto T, Tanaka H. Prostate-specific antigen levels and prognosis in patients with hormone-refractory prostate cancer treated with low-dose dexamethasone. Urol Int. 2002;68:10–5.

    Article  CAS  Google Scholar 

  22. Yano A, Fujii Y, Iwai A, Kageyama Y, Kihara K. Glucocorticoids suppress tumor angiogenesis and in vivo growth of prostate cancer cells. Clin Cancer Res. 2006;12:3003–9.

    Article  CAS  Google Scholar 

  23. Dabkara D, Ganguly S, Biswas B, Ghosh J. Metronomic therapy in metastatic castrate-resistant prostate cancer: experience from a tertiary cancer care center. Indian J Cancer. 2018;55:94–7.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical Oncology Division and Breast Unit, Sen. Antonio Perrino Hospital, S.S. 7, 72100, Brindisi, Italy

    Nicola Calvani, Laura Orlando, Palma Fedele & Saverio Cinieri

  2. Department of Oncology, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy

    Franco Morelli

  3. Medical Oncology Unit, IRCCS Giovanni Paolo II, Bari, Italy

    Emanuele Naglieri

  4. Medical Oncology Unit, Sacro Cuore di Gesù Hospital, Gallipoli, Italy

    Antonio Gnoni

  5. Medical Oncology Department, V. Fazzi Hospital, Lecce, Italy

    Vincenzo Emanuele Chiuri

Authors
  1. Nicola Calvani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Franco Morelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Emanuele Naglieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Antonio Gnoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Vincenzo Emanuele Chiuri
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Laura Orlando
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Palma Fedele
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Saverio Cinieri
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nicola Calvani.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

This study was approved by the Independent Medical Ethics Committee of ASL Brindisi. Because this was a retrospective study, formal consent was required only for those participants still alive at the time of data collection.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Calvani, N., Morelli, F., Naglieri, E. et al. Metronomic chemotherapy with cyclophosphamide plus low dose of corticosteroids in advanced castration-resistant prostate cancer across the era of taxanes and new hormonal drugs. Med Oncol 36, 80 (2019). https://doi.org/10.1007/s12032-019-1304-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-019-1304-y

Keywords

Search

Navigation