Methotrexate therapy leading to a rapid progression of a previously indolent prostate cancer: Is immunosuppression to blame?

Abstract

Methotrexate therapy has been associated with occurrence and/or accelerated progression of malignancies. We describe a patient who developed widespread bone metastases of a previously confined to the prostate gland prostate cancer shortly after starting methotrexate therapy for rheumatoid arthritis and large granular lymphocyte leukemia. We believe an immunosuppressive milieu brought on by the methotrexate use in this case is responsible for the rapid progression of prostate cancer leading to the patient's demise. To the best of our knowledge, no association has been made to date between the therapy with methotrexate and a fulminant course of a previously indolent prostate cancer. Given its utilization in a variety of benign and malignant conditions and the ageing population, caution is advised with the use of this agent, especially in the presence of an underlying malignancy.

Keywords

Methotrexate prostate cancer rheumatoid arthritis large granular lymphocyte leukemia

Get full access to this article

View all access options for this article.

References

Genestier

Paillot

Fournel

. Immunosuppressive properties of methotrexate: apoptosis and clonal deletion of activated peripheral T cells. J Clin Invest 1998; 102: 322–328.

Salloum

Cooper

Howe

. Spontaneous regression of lymphoproliferative disorders in patients treated with methotrexate for rheumatoid arthritis and other rheumatic diseases. J Clin Oncol 1996; 14: 1943–1949.

Rannikko

Krogerus

Nyberg

. Rapid progression of small cell carcinoma in a renal transplant recipient. Int J Urol 2006; 13: 817–819.

Kessler

Jay

Molle

. Excess risk of cancer in renal transplant patients. Transpl Int 2006; 19: 908–914.

US Renal Data System (USRDS). In: Health

NIo

(ed.) Annual Report: Atlas of end stage renal disease in the United States, Besthesda, MD: National Institutes of Diabetes and Digestive and Kidney Disease, 2007.

Crum

Spencer

Amling

. Prostate carcinoma among men with human immunodeficiency virus infection. Cancer 2004; 101: 294–299.

Pollard

. Enhancement of metastasis of prostate adenocarcinoma cells by immune-suppressive cyclosporine A. Cancer Lett 1997; 111: 221–224.

David

Morris

Steffen

. Mycophenolate mofetil versus azathioprine is associated with decreased acute rejection, late acute rejection, and risk for cardiovascular death in renal transplant recipients with pre-transplant diabetes. Clin Transplant 2005; 19: 279–285.

Dasanu

Bauer

Ichim

. Rapidly fatal acute ATLL emerging after methotrexate therapy for disseminated psoriasis. Clin Lymphoma Myeloma Leuk 2012; 12: 76–78.

10.

Vial

Descotes

. Immunosuppressive drugs and cancer. Toxicology 2003; 185: 229–240.

11.

Nielsen

Albertsen

Bendtzen

. Methotrexate induces poly(ADP-ribose) polymerase-dependent, caspase 3-independent apoptosis in subsets of proliferating CD4+ T cells. Clin Exp Immunol 2007; 148: 288–295.

12.

Wada

Yoshimura

Hipkiss

. Cyclophosphamide augments antitumor immunity: studies in an autochthonous prostate cancer model. Cancer Res 2009; 69: 4309–4318.

13.

Salinas-Carmona

Perez

Galan

. Immunosuppressive drugs have different effect on B lymphocyte subsets and IgM antibody production in immunized BALB/c mice. Autoimmunity 2009; 42: 537–544.

14.

Nelius

Rinard

Filleur

. Oral/metronomic cyclophosphamide-base chemotherapy as option for patients with castration-refractory prostate cancer: review of literature. Cancer Treat Rev 2001; 37: 444–455.

15.

Ladoire

Eymard

Zanetta

. Metronomic cyclophosphamide prednisolone chemotherapy is an effective treatment for metastatic hormone-refractory prostate cancer after docetaxel failure. Anticancer Res 2010; 30: 4317–4323.