Skip to main content

Advertisement

Log in

Aplastic anemia in a lung adenocarcinoma patient receiving pemetrexed

  • SHORT REPORT
  • Published:
Investigational New Drugs Aims and scope Submit manuscript

Summary

Pemetrexed (PEM) is an antimetabolite drug that interferes with enzymes involved in DNA synthesis and also the folate-dependent metabolic processes necessary for DNA replication and homocysteine homeostasis. Continuation maintenance with PEM after induction therapy with PEM plus cisplatin has been the standard form of first-line chemotherapy for advanced non-squamous non-small cell lung cancer. The regimen has a low incidence of bone marrow suppression, and the incidences of anemia, leukopenia, neutropenia and thrombocytopenia exceeding grade 3 are less than 5%. Here we report a 68-year-old Japanese man with stage IIIB (cT4N3M0) lung adenocarcinoma who received 4 cycles of chemotherapy with PEM 500 mg/m2 and cisplatin 75 mg/m2 every three weeks, which resulted in a partial response, and then continued to receive maintenance PEM monotherapy. After 11 cycles of PEM maintenance therapy, the patient’s platelet count decreased, and progressed to pancytopenia within two months. A bone marrow puncture revealed replacement with fatty marrow. As other diseases possibly responsible for pancytopenia were ruled out, we diagnosed the patient as having aplastic anemia. This is the first reported case of aplastic anemia to have occurred during PEM therapy. Clinicians should bear in mind that PEM can potentially trigger severe pancytopenia, including aplastic anemia.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Paz-Ares L, de Marinis F, Dediu M, Thomas M, Pujol J-L, Bidoli P et al (2012) Maintenance therapy with PEM plus best supportive care versus placebo plus best supportive care after induction therapy with PEM plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol 13:247–255

    Article  CAS  Google Scholar 

  2. Issaragrisil S, Kaufman DW, Anderson T, Chansung K, Thamprasit T, Sirijirachai J et al (1997) Low drug attributability of aplastic anemia in Thailand. Blood 89:4034–4039

    CAS  PubMed  Google Scholar 

  3. Bacigalupo A, Oneto R, Bruno B, Socié G, Passweg J, Locasciulli A et al (2000) Current results of bone marrow transplantation in patients with acquired severe aplastic anemia: report of the European Group for Blood and Marrow transplantation. Acta Haematol 103:19–25

    Article  CAS  Google Scholar 

  4. Lim AYN, Gaffney K, Scott DGI (2005) Methotrexate-induced pancytopenia: serious and under-reported? Our experience of 25 cases in 5 years. Rheumatology 44:1051–1055

    Article  CAS  Google Scholar 

  5. Fernando GI, Sahar EM, Shiri S, Hazem A, Amer KS, Simon B, et al. (2014) Methotrexate-induced pancytopenia. Case Reports in Rheumatology 2014: 679580.

  6. Kremer J, Galivan J, Streckfuss A, Kamen B (1986) Methotrexate metabolism analysis in blood and liver of rheumatoid arthritis patients. Association with hepatic folate deficiency and formation of polyglutamates. Arthritis Rheum 29:832–835

    Article  CAS  Google Scholar 

  7. Koizumi S, Curt GA, Fine RL, Griffin JD, Chabner BA (1985) Formation of methotrexate polyglutamates in purified myeloid precursors cells from normal human bone marrow. J Clin Invest 75:1008–1014

    Article  CAS  Google Scholar 

  8. Rosenblatt DS, Whitehead VM, Dupont MM, Vuchich MJ, Vera N (1978) Synthesis of methotrexate polyglutamates in cultured human cells. Mol Pharmacol 14:210–214

    CAS  PubMed  Google Scholar 

  9. Robert A Brodsky, Richard J Jones (2005) Aplastic anaemia. Lancet 365: 1647–1656.

  10. Parmaceuticals and Medical Devices Agency (2008)

Download references

Acknowledgements

There is no source to funding to acknowledge.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Takaaki Tokito.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

For this type of study, formal consent is not required.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Matama, G., Tokito, T., Takeoka, H. et al. Aplastic anemia in a lung adenocarcinoma patient receiving pemetrexed. Invest New Drugs 35, 662–664 (2017). https://doi.org/10.1007/s10637-017-0462-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10637-017-0462-z

Keywords

Navigation