Advertisement

Medical Oncology

, 36:80 | Cite as

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

  • Nicola CalvaniEmail author
  • Franco Morelli
  • Emanuele Naglieri
  • Antonio Gnoni
  • Vincenzo Emanuele Chiuri
  • Laura Orlando
  • Palma Fedele
  • Saverio Cinieri
Original Paper
  • 34 Downloads

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.

Keywords

Prostate cancer Castration-resistant Cyclophosphamide Metronomic chemotherapy 

Notes

Compliance with ethical standards

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.

References

  1. 1.
    Kerbel RS, Kamen BA. The anti-angiogenic basis of metronomic chemotherapy. Nat Rev Cancer. 2004;4:423–36.CrossRefGoogle Scholar
  2. 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.CrossRefGoogle Scholar
  3. 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.CrossRefGoogle Scholar
  4. 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.CrossRefGoogle Scholar
  5. 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.CrossRefGoogle Scholar
  6. 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.CrossRefGoogle Scholar
  7. 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.CrossRefGoogle Scholar
  8. 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.CrossRefGoogle Scholar
  9. 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.CrossRefGoogle Scholar
  10. 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.CrossRefGoogle Scholar
  11. 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.CrossRefGoogle Scholar
  12. 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.PubMedGoogle Scholar
  13. 13.
    Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1990;82:4–6.CrossRefGoogle Scholar
  14. 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. 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.CrossRefGoogle Scholar
  16. 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.CrossRefGoogle Scholar
  17. 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.CrossRefGoogle Scholar
  18. 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.CrossRefGoogle Scholar
  19. 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.CrossRefGoogle Scholar
  20. 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.CrossRefGoogle Scholar
  21. 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.CrossRefGoogle Scholar
  22. 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.CrossRefGoogle Scholar
  23. 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.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Medical Oncology Division and Breast UnitSen. Antonio Perrino HospitalBrindisiItaly
  2. 2.Department of OncologyIRCCS Casa Sollievo della SofferenzaSan Giovanni RotondoItaly
  3. 3.Medical Oncology UnitIRCCS Giovanni Paolo IIBariItaly
  4. 4.Medical Oncology UnitSacro Cuore di Gesù HospitalGallipoliItaly
  5. 5.Medical Oncology DepartmentV. Fazzi HospitalLecceItaly

Personalised recommendations