Ifosfamide

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.

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)

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!

• Blood and lymphatic disorders: Leukopenia (dose-limiting bone marrow depression) is common,
• Nervous system disorders: Encephalopathy is also typical with ifosfamide administration, occurring in up to 50% of patients (Ajithkumar T et al 2007).
• Cardiac disease: arrhythmias
• Gastrointestinal disorders: Nausea, vomiting.
• Skin and subcutaneous tissue disorders: hair loss, hyperpigmentation of nails(melanonychia) and palms (Teresi ME et al 1993).
• Kidney and urinary tract diseases: Hemorrhagic cystitis (Klastersky J 2003): mandatory is the administration of MESNA (mercapto-ethanesulfonate sodium);
• In a larger study (Mashhadi MA et al 2011), the following dose-dependent pathological renal parameters were detected: proteinuria (15.5%), glycosuria (7.8%), increase in serum creatinine level (2.2%), hematuria (14.4%).
• Prospective pharmacon-induced diseases: possible development of secondary neoplasms, especially leukemias and bladder tumors.
• Vaccinations with inactivated vaccines are not effective under ifosfamide treatment due to its immunosuppressive and cytostatic effects.
• Vaccinations with live vaccines are potentially dangerous due to the cytostatic and immunosuppressive effects of ifosfamide and should be omitted.

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.

Holoxan®

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/