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Immune system modulators
Published in Gabriel Virella, Medical Immunology, 2019
Richard M. Silver, Stephen Elmore
Cyclophosphamide is an alkylating agent that inhibits both the cellular and humoral immune responses. After administration, cyclophosphamide is broken down into active metabolites that prevent DNA replication, causing the death of both dividing and nondividing T and B lymphocytes. Initially, cyclophosphamide was administered as a daily oral agent. However, intravenous (IV) cyclophosphamide pulses are now favored, as the IV form has a lower risk of toxicity, including fewer incidents of hemorrhagic cystitis and bladder cancer. The IV dosing for cyclophosphamide is typically carried out on an intermittent basis (usually every few weeks to monthly, depending on the cycle utilized). Side effects associated with cyclophosphamide include hematologic abnormalities (particularly leukopenia), nausea and vomiting, and diminished fertility in both male and female patients, in addition to the previously mentioned bladder toxicity. The use of Mesna, a sulfhydryl compound, administered before and after IV cyclophosphamide infusions, may lower the risk of bladder toxicity by binding to and neutralizing the toxic effects of acrolein and other urotoxic by-products of cyclophosphamide. Cyclophosphamide has found a role in the treatment of several autoimmune diseases resistant to steroid and other immunosuppressive treatment, including lupus nephritis, SSc-ILD, and ANCA-associated vasculitides.
Interstitial lung disease associated with connective tissue disorders
Published in Muhunthan Thillai, David R Moller, Keith C Meyer, Clinical Handbook of Interstitial Lung Disease, 2017
Deborah Assayag, Aryeh Fischer
Given the substantial toxicity associated with CYC (e.g. bone marrow suppression, infection risk, malignancy risk, bladder toxicity), it is usually considered a short-term option, and its use is often limited to those with more severe forms of CTD-ILD (62). CYC is equally effective in either oral or intravenous form. The intravenous form has less bladder toxicity and is generally considered as a safer option than the oral form. With intravenous therapy, a typical first infusion dose is 500 mg/m2, and subsequent infusions are dose escalated based on tolerability and the white blood cell count nadir. Peak dosing is often ~750–1000 mg/m2. Commonly, MESNA (administered at approximately 40% of the cumulative CYC dose before and after each CYC infusion) and robust hydration are utilized to minimize bladder toxicity. Judicious use of anti-emetic therapy is often required. Given the potential for adverse side effects and nuances associated with dose escalation, and institution of anti-emetics, infusions are often coordinated via rheumatology and infused in experienced centres. When CYC is given orally, the initial dose begins at 25–50 mg/day and dose-escalated as tolerated towards a recommended goal maintenance dose of ~2 mg/kg/day. The dosing regimen should be carefully titrated to individual tolerance, disease responsiveness and disease severity. Frequent assessment of the complete blood count and urinalysis is important to assess for myelosuppression and bladder toxicity, respectively (88).
Principles of Systemic Cancer Therapy
Published in Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George, The Scientific Basis of Urology, 2010
Christina Thirlwell, John Bridgewater, Judith Cave
The toxicity of certain drugs can be reduced by techniques to protect normal tissue. For example, cyclophosphamide and ifosfamide produce acrolein, which is an irritant metabolite excreted through the bladder. Mesna is a thiol compound that acts as a reducing agent, and when given with cyclophosphamide reacts with acrolein in the urinary tract and helps prevent chemical cystitis (44).
Potential applications of PEGylated green gold nanoparticles in cyclophosphamide-induced cystitis
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2022
Bushra Shal, Safa Amanat, Ashraf Ullah Khan, You Jeong Lee, Hussain Ali, Fakhar ud Din, Youmie Park, Salman Khan
Cyclophosphamide (CYP) is a cytotoxic alkylating agent, belonging to oxazophorine group having reported efficacy in numerous human malignancies [1]. Detrimental toxicities such as immunosuppression and haemorrhagic cystitis are associated with this anti-cancer agent reducing its clinical usefulness [2,3]. Numerous therapeutic agents have been evaluated experimentally and clinically against CYP-induced cystitis, but none has been proved to have complete protective effect. Clinically, sodium-2-mercaptoethane sulphonate (mesna) is used to detoxify acrolein; however, dose-dependent side-effects still occur with its use. Therefore, in order to enhance the effect of CYP and inhibition of cystitis along with reduction in bladder pain, there is a need for the development of a potential alternative therapy for cystitis. In the current study, gold nanoparticles (AuNPs) have been prepared owing to its diverse biomedical applications such as photothermal therapy, photodynamic therapy, drug delivery, X-ray imaging, and sensing [4]. The synthesis of AuNPs is simple, its optical and physicochemical properties contribute to diverse nanotechnology applications. For the synthesis of AuNPs, green synthetic strategy using plant extract have attracted researchers’ attention due to sustainability initiatives [5,6].
Malignant peripheral nerve sheath tumor of the orbit: a case report and review of the literature
Published in Orbit, 2022
Kara E. Jones, Ami Patel, Mary G. Kunesh, Bradley A. Thuro
However, after further discussion with her oncologist, adjuvant radiotherapy was begun within 4 weeks of her exenteration due to the high likelihood of a second recurrence. Wound dehiscence was noted in the orbit within the first week of radiation treatment; this was managed with conservative wound care measures to allow completion of radiation therapy and subsequent chemotherapy. The patient concluded her 50 Gy of radiation to the right orbit. At the conclusion of her radiation treatment, there was clinical evidence of submandibular lymph node metastasis and repeat CT showed new bilateral pulmonary nodules and an abdominal mass consistent with metastasis. The patient was initiated on a six-cycle course of chemotherapy consisting of doxorubicin, ifosfamide, and mesna to which her metastatic lesions partially responded. She underwent a secondary reconstruction of her orbit with an anterolateral thigh free flap which healed well.
Definitive therapy for squamous cell carcinoma of the anus with synchronous metastases – a report from the Danish Anal Cancer Group
Published in Acta Oncologica, 2022
Karen Lycke Wind, Eva Serup-Hansen, Birgitte Mayland Havelund, Lisbeth Riber, Camilla Jensenius Skovhus Kronborg, Anders Jakobsen, Karen-Lise Garm Spindler
Patients were treated with cisplatin and 5-flourouracil based ICT prior to (chemo)radiotherapy. Two regimens were used: either cisplatin (37.5 mg/m2 intravenously (iv.), ifosfamide (2.0 mg/m2 iv.), and 5-flourouracil (500 mg/m2 iv.) day one and two in combination with leucovorin (60 mg/m2 iv.) (CILF) or cisplatin (60 mg/m2 iv.) administered at day one and 5-floururacil (1000 mg/m2) administered with 24 h continuous infusion days 1–4 (cis-5-FU). Supportive therapy to patients receiving ifosfamide included mesna (500 mg/m2 iv. administered before ifosfamide and 1 g/m2 orally at two and six hours after ifosfamide). Hydration and antiemetic were administered by local protocol. Granulocyte colony-stimulating factor (G-CSF) was not used routinely but administered at the discretion of the physician.