Skip to main content
Top
Published in: Medical Oncology 9/2019

01-09-2019 | Prostate Cancer | Original Paper

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

Authors: Nicola Calvani, Franco Morelli, Emanuele Naglieri, Antonio Gnoni, Vincenzo Emanuele Chiuri, Laura Orlando, Palma Fedele, Saverio Cinieri

Published in: Medical Oncology | Issue 9/2019

Login to get access

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.
Literature
1.
go back to reference Kerbel RS, Kamen BA. The anti-angiogenic basis of metronomic chemotherapy. Nat Rev Cancer. 2004;4:423–36.CrossRef Kerbel RS, Kamen BA. The anti-angiogenic basis of metronomic chemotherapy. Nat Rev Cancer. 2004;4:423–36.CrossRef
2.
go back to reference 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.CrossRef 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.CrossRef
3.
go back to reference 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.CrossRef 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.CrossRef
4.
go back to reference 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.CrossRef 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.CrossRef
5.
go back to reference 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.CrossRef 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.CrossRef
6.
go back to reference Glode LM, Barqawi A, Crighton F, Crawford ED, Kerbel R. Metronomic therapy with cyclophosphamide and dexamethasone for prostate carcinoma. Cancer. 2003;98:1643–8.CrossRef Glode LM, Barqawi A, Crighton F, Crawford ED, Kerbel R. Metronomic therapy with cyclophosphamide and dexamethasone for prostate carcinoma. Cancer. 2003;98:1643–8.CrossRef
7.
go back to reference 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.CrossRef 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.CrossRef
8.
go back to reference 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.CrossRef 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.CrossRef
9.
go back to reference 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.CrossRef 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.CrossRef
10.
go back to reference 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.CrossRef 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.CrossRef
11.
go back to reference 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.CrossRef 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.CrossRef
12.
go back to reference 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.PubMed 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.PubMed
13.
go back to reference Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1990;82:4–6.CrossRef Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1990;82:4–6.CrossRef
14.
go back to reference 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. 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.
15.
go back to reference 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.CrossRef 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.CrossRef
16.
go back to reference 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.CrossRef 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.CrossRef
17.
go back to reference 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.CrossRef 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.CrossRef
18.
go back to reference 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.CrossRef 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.CrossRef
19.
go back to reference 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.CrossRef 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.CrossRef
20.
go back to reference 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.CrossRef 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.CrossRef
21.
go back to reference 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.CrossRef 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.CrossRef
22.
go back to reference 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.CrossRef 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.CrossRef
23.
go back to reference 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.CrossRef 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.CrossRef
Metadata
Title
Metronomic chemotherapy with cyclophosphamide plus low dose of corticosteroids in advanced castration-resistant prostate cancer across the era of taxanes and new hormonal drugs
Authors
Nicola Calvani
Franco Morelli
Emanuele Naglieri
Antonio Gnoni
Vincenzo Emanuele Chiuri
Laura Orlando
Palma Fedele
Saverio Cinieri
Publication date
01-09-2019
Publisher
Springer US
Published in
Medical Oncology / Issue 9/2019
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-019-1304-y

Other articles of this Issue 9/2019

Medical Oncology 9/2019 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.