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Antineoplastic Drugs during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Cyclophosphamide (Cytoxan, Neosar), an alkylating agent, is metabolized mainly by the liver to several active alkylating metabolites (phosphoramide mustard and acrolein) that cause tumor cell DNA crosslinking. Cyclophosphamide is used to treat several types of cancer, including (1) certain forms of acute and chronic leukemia, (2) ovarian, (3) multiple myeloma, (4) mycosis fungoides, and (5) breast carcinoma. It has also been used in treatment of cancers of the bladder, cervix, colorectum, endometrium, Ewing’s sarcoma, head and neck, lymphomas, kidney, lung, osteosarcoma, pancreas, and trophoblastic tumors.
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
In addition to its use in cancer chemotherapy, cyclophosphamide is also used to treat some autoimmune disorders. Although the mechanisms underlying these anti-immune effects are not fully understood, several possibilities have been suggested, including the elimination of T regulatory cells (e.g., CD4+/CD25+ T cells), induction of T-cell growth factors (IFNs), or enhanced grafting of adoptively transferred tumor-reactive effector T cells.
Respiratory, endocrine, cardiac, and renal topics
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
Cyclophosphamide is administered orally or intravenously. After intravenous injection, the elimination half-life of cyclophosphamide ranges from 4 to 10 hours. The peak of alkylating molecules is 1 to 2 hours after the cyclophosphamide peak. Their half-life is comparable to that of the prodrug. The 4 hydroxy-cyclophosphamide metabolite is weakly bound to plasma proteins. Brain distribution of cyclophosphamide and its metabolites is moderate with a CSF to plasma ratio of approximately 0.2. Renal excretion is the main route of elimination of cyclophosphamide and its metabolites.
Fixed duration vs. prolonged duration treatment after first line therapy in patients with systemic light chain amyloidosis
Published in Amyloid, 2022
Alfonso Rivera Duarte, Donna Reece, Xuan Li, Wei Xu, Harminder Paul, Esther Masih-Khan, Andrew Winter, Rodger Tiedemann, Anca Prica, Christine Chen, Suzanne Trudel, Vishal Kukreti
For study purposes, given that there is no formal definition for consolidation nor maintenance in AL amyloidosis, we considered any form of a low-intensity post-first line of treatment as prolonged duration treatment. Prolonged duration treatment was defined as continuous, single-agent therapy after the first line of treatment, with a duration of at least three cycles regardless of the drug used, and given until progression, maximum benefit, or unacceptable toxicity. As well, prolonged treatment must have commenced within 6 months after frontline treatment and the patient must not have met criteria for hematological or organ progression as per current guidelines at the time of commencing prolonged duration treatment. The prolonged duration treatment administration details including a drug used, dosage, and schedule of administration were entirely based on the treating physician’s discretion. Drugs used as prolonged treatment after the first line were bortezomib; mainly administrated either days 1, 8, and 15 of 28 days cycle or every 2 weeks with dosing that ranged between 0.8 and 1.3 mg/m2. For lenalidomide, the most frequent schedule was usually days 1–21 of a 28 days cycle and doses ranged between 5 mg every 48 h to 10 mg a day. For the patients that received cyclophosphamide, the dosing was 25–50 mg daily.
Intracellular activation of 4-hydroxycyclophosphamide into a DNA-alkylating agent in human leucocytes
Published in Xenobiotica, 2021
Minghan Yong, Kathryn Elisa Burns, Janak de Zoysa, Nuala Ann Helsby
Cyclophosphamide, first approved in 1959, is currently used to treat cancers, particularly lymphomas and breast cancer. It is also used to treat autoimmune diseases, including systemic lupus erythematosus, vasculitis and membranous nephropathy. Despite its age and the advent of many alternative treatments, cyclophosphamide has continued to be an important and relevant therapeutic agent. This is due in part to its efficient killing of neoplastic lymphoid cells, as well as its immunomodulatory properties. Cyclophosphamide has selectivity for mature immunocytes (e.g. T- and B-lymphocytes) but spares the early haematopoietic progenitors and stem cells at doses between 500 and 1000 mg/m2, making it useful for control of some autoimmune diseases. It can also induce peripheral immune tolerance by preventing the clonal proliferation of reactive T-lymphocytes, which has led to the use of a short-pulse of post-transplant cyclophosphamide (PTCy) to prevent graft-versus host disease (Kato et al. 2019). This short-pulse (1-2 day, low dose ∼1000 mg/m2) PTCy approach is now established for allogeneic-haematopoietic stem cell transplant (HSCT) and is also under investigation for kidney transplantation. Cyclophosphamide is also used for conditioning (lymphodepletion) prior to chimeric antigen receptor-T cell (CAR-T) immunotherapy of haematological malignancies (Hirayama et al. 2019).
Symmetric polyneuropathy after viral symptomatology – not always Guillain-Barré Syndrome
Published in Acta Clinica Belgica, 2021
Michiel Keyzer, Anne Hoorens, Jo Van Dorpe, Anne-Marie Bogaert
Remission is achieved when systemic symptoms and signs resolve and the urine analysis is free of microscopic haematuria (even if there is persistent proteinuria or even slowly worsening renal insufficiency). As a maintenance therapy for AAV, the European League Against Rheumatism (EULAR) recommends low-dose glucocorticoids in association with either azathioprine (2 mg/kg/day), rituximab, methotrexate or mycophenolate mofetil. Most recommendations prefer azathioprine. Cyclophosphamide as maintenance therapy is not indicated because of its toxicity. This maintenance therapy should be administered for at least 18–24 months and even 36 months if the AAV is PR3 positive, as early withdrawal of therapy is associated with an increased risk of relapse. The most important side effect of azathioprine is bone marrow suppression. This in combination with low-dose glucocorticoids makes the patient vulnerable to infections [19,20].