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Abstract

Cyclophosphamide (CTX) is an alkylating cytotoxic agent that primarily targets proliferating lymphocytes. It has been widely used as a chemotherapeutic and disease-modifying agent against several malignancies, lymphomas, and some autoimmune diseases. Depending on the dose and timing of administration, CTX can also improve immune responses. Although the hypothesized mechanism of tumor specificity (activation by cancer cell phosphamidases) turned out to be irrelevant to its activity, it was initially created to selectively target cancer cells. Nonetheless, cyclophosphamide's distinct cytotoxic properties are attributable to its unique metabolism and inactivation by aldehyde dehydrogenase. This review was conducted to identify cyclophosphamide-related toxicities as reported in prior research on that topic. Ninety-one articles were obtained, but only six studies met the inclusion criteria. The studies included a total of 3,531 participants. Cyclophosphamide was linked to a number of toxicities, including liver toxicity, urotoxicity, cardiac toxicity, hematological, and non-hematological toxicities. The toxicity of cyclophosphamide varied depending on the regimen and combination drugs, as well as some gene variants.

Keywords

Cyclophosphamide, toxicity, predictors, outcomes, cancer therapy; drug stability; prodrugs; vesicular systems; nanoparticles; trastuzumab

Introduction

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Cyclophosphamide (CTX) belongs to a class of cytotoxic alkylating nitrogen mustard chemicals, and is also marketed under the trade names ENDOXAN®, CYTOXAN®, ROCYTOX®, and NEOSAR®. The amount of CTX given in animal models and in humans varies according on the treatment objective and plan. Due to its selective cytotoxicity on lymphocytes without being myeloablative, high-dose CTX therapy (≥200 mg/kg) was originally developed as a conditioning regimen for allogeneic bone marrow transplantation to prevent graft-versus-host disease (GvHD).[1] One of the greatest anti-cancer medications ever created is cyclophosphamide. Even fifty years after its invention, it is still widely used in chemotherapy and in the conditioning and mobilization procedures for blood and marrow transplantation (BMT). Cyclophosphamide was found to be the most effective molecule after testing 1,000 chosen compounds and antibiotics against 33 tumors. In 1958, the first clinical trials of cyclophosphamide for the treatment of cancer were carried out, and in 1959, the FDA authorized it as the eighth cytotoxic anticancer drug. [6]

Reference

  1. Brode S, Cooke A. Immune-potentiating effects of the chemotherapeutic drug cyclophosphamide. Department of Pathology, University of Cambridge, Cambridge, UK.
  2. Emadi A, Jones RJ, Brodsky RA. Cyclophosphamide and cancer: golden anniversary.
  3. Emadi A, Jones RJ, Brodsky RA. Cyclophosphamide and cancer: golden anniversary. Division of Adult Hematology; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
  4. Mills BA, Roberts RW. Cyclophosphamide-induced cardiomyopathy: a report of two cases and review of the English literature.
  5. Zhao YR, Song HM, Ni L. Cyclophosphamide for the treatment of acute lymphoblastic leukemia: a protocol for systematic review.
  6. American Cancer Society. What is cancer? Available from: https://www.cancer.org/cancer/understanding-cancer/history-of-cancer/what-is-cancer.html. Accessed 2025 Nov 14.
  7. Ioele G, Chieffallo M, Occhiuzzi MA, De Luca M, Garofalo A, Ragno G, Grande F. Anticancer drugs: recent strategies to improve stability profile, pharmacokinetic and pharmacodynamic properties.
  8. 1mg.Cyclophosphamide. Availablefrom: https://www.1mg.com/generics/cyclophosphamide209671. Accessed 2025 Nov 14.
  9. Google Search. Advantages of cyclophosphamide. Available from: https://www.google.com/search?q=advantages+of+cyclophosphamide. Accessed 2025 Nov 14.
  10. Google Search. Disadvantages of cyclophosphamide. Available from: https://www.google.com/search?q=disadvantage+of+cyclophosphamide. Accessed 2025 Nov 14.
  11. Google Search. Future direction of cyclophosphamide drug. Available from: https://www.google.com/search?q=future+direction+of+cyclophosphamide+drug. Accessed 2025 Nov 14.
  12. Google Search. Precautions of cyclophosphamide. Available from: https://www.google.com/search?q=precaution+of+cyclophospanamide. Accessed 2025 Nov 14.

Photo
Mohalkar Krushna
Corresponding author

Dr. N. J. Paulbudhe College of Pharmacy, Ahilyanagar

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Dr. Tarde Vijay
Co-author

Dr. N. J. Paulbudhe College of Pharmacy, Ahilyanagar

Photo
Dahatonde Abhijit
Co-author

Dr. N. J. Paulbudhe College of Pharmacy, Ahilyanagar

Photo
Munfan Sumit
Co-author

Dr. N. J. Paulbudhe College of Pharmacy, Ahilyanagar

Mohalkar Krushna*, Dahatonde Abhijit, Munfan Sumit, Dr. Tarde Vijay, Beyond Alkylation ? Cyclophosphamide?s Expanding Role in Cancer Therapy and Immunomodulation, Int. J. Sci. R. Tech., 2025, 2 (11), 636-646. https://doi.org/10.5281/zenodo.17682329

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