Ifosfamide

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Synonym(s)

CAS number: 3778-73-2; Ifosfamide; Ifosfamidum; (RS)-3-(2-chloroethyl)-2-[(2-chloroethyl)amino]-2H-1,3,2-oxazaphosphinane 2-oxide (IUPAC)

Definition
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Ifosfamide, an intravenously administered nitrogen-lost derivative (molecular formula C7H15Cl2N2O2P) belongs to the cytostatic alkyl agents. Together with trofosfamide it is a cyclophosphamide analogue and is bioactivated and eliminated in a similar way. Ifosfamide andTrofosamide have the same spectrum of action and side effects as cyclophosphamide. Ifosfamide is used as a cytostatic drug for a number of malignant tumours. It is usually used in combination with other cytostatic drugs.

Indication
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Adults

  • Soft Tissue Sarcomas
  • Osteosarcoma - IP (Ifosfamide, Cisplatin)
  • Non-Hodgkin's lymphomas: Combination chemotherapy in patients with highly malignant non-Hodgkin's lymphomas that do not respond or respond insufficiently to initial therapy; combination therapy in patients with recurrent tumors
  • Ewing sarcoma - VAI (vincristine, adriamycin, ifosfamide)
  • Breast cancer: Palliative therapy for advanced, refractory or recurrent breast cancer
  • non-small cell lung cancer: single or combination chemotherapy of patients with inoperable or metastatic tumours
  • small cell bronchial carcinoma: combination chemotherapy
  • Testicular tumours: Combination chemotherapy in patients with advanced tumours in stages II - IV according to TNM classification (seminomas and non-seminomas), which do not respond or do not respond sufficiently to initial chemotherapy

Children and young people

  • Soft tissue sarcomas such as rhabdomyosarcoma, leiomyosarcoma - VAI (vincristine, adriamycin, ifosfamide), VAIA (vincristine, adriamycin, ifosfamide, actinomycin D)
  • Non-Hodgkin's lymphoma
  • Ewing sarcoma - VAI (vincristine, adriamycin, ifosfamide), VAIA (vincristine, adriamycin, ifosfamide, actinomycin D)
  • Germ cell tumor - PEI (cisplatin, etoposide, ifosfamide)
  • Osteosarcoma - PAIM (cisplatin, adriamycin, ifosfamide, MTX)

Dosage and method of use
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Most common dosage in monotherapy for adults: fractional application 1.2 - 2.4 g ifosfamide /m2 body surface area (KOF) (= 60 mg / kg body weight (KG)) i. v. / day for 5 consecutive days.

Alternatively: administration of a high single dose, usually as a 24-hour continuous infusion 5 g ifosfamide /m2 KOF (125 mg / kg bw) i. v.

Note: in case of high single dose, stronger hemato-, uro-, nephro- and CNS-toxicity must be expected!

Undesirable effects
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  • Diseases of the blood and lymphatic system: leukopenia (dose-limiting bone marrow depression) is common,
  • Diseases of the nervous system: Typical for ifosfamide administration is also encephalopathy, which occurs in up to 50 % of patients (Ajithkumar T et al. 2007).
  • Heart diseases: Arrhythmias
  • Diseases of the gastrointestinal tract: nausea, vomiting
  • Diseases of the skin and subcutaneous tissues: hair loss, hyperpigmentation of nails(melanonychia) and palms (Teresi ME et al. 1993)
  • Diseases of the kidneys and urinary tract: haemorrhagic cystitis (Klastersky J 2003): the administration of MESNA (mercapto-ethanesulfonate sodium) is mandatory;
  • In a larger study (Mashhadi MA et al. 2011), the following dose-dependent pathological kidney parameters were detected: proteinuria (15.5%), glycosuria (7.8%), increase in serum creatinine level (2.2%), hematuria (14.4%).
  • Prospective pharmacone-induced diseases: possible development of secondary neoplasia, especially leukaemias and bladder tumours
  • Vaccinations with dead vaccines are not effective under ifosfamide treatment because of its immunosuppressive and cytostatic effect.
  • Vaccinations with live vaccines are potentially dangerous due to the cytostatic and immunosuppressive effect of ifosfamide and should therefore be avoided.

Contraindication
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Pregnancy. Pregnancy should be ruled out before ifosfamide therapy, an existing pregnancy is a contraindication against the use of ifosfamide. During therapy sufficient contraceptive measures should be used to prevent pregnancy.

Preparations
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Holoxan®

Literature
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  1. Ajithkumar T et al (2007) Ifosfamide encephalopathy. Clin Oncol (R Coll Radiol) 19:108-114. https://pubmed.ncbi.nlm.nih.gov/17355105/
  2. European Pharmacopoeia Commission (eds.): EUROPEAN PHARMACCOPE 6th Edition. Volume 6.0-6.3
  3. Klastersky J (2003) Side effects of ifosfamide. Oncology 65 Suppl 2:7-10. https://pubmed.ncbi.nlm.nih.gov/14586140/
  4. Mashhadi MA et al (2011) Ifosfamide nephropathy in patients with sarcoma. Iran J Kidney Dis 5:238-241. https://pubmed.ncbi.nlm.nih.gov/21725180/
  5. Sarosy G (1989) Ifosfamide--pharmacologic overview. Semin Oncol 16(1 Suppl 3):2-8.
  6. Maryadele J. ONeil: The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals. Published by: Merck & Co., Inc. 14th edition. Elsevier, Whitehouse Station
  7. Teresi ME et al (1993) Ifosfamide-induced hyperpigmentation. Cancer 71:2873-2875. https://pubmed.ncbi.nlm.nih.gov/8385568/

Outgoing links (2)

Hyperpigmentation; Melanonychia;

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Last updated on: 29.10.2020