# Ifosfamide

Source: https://onco.cc/drugs/ifosfamide/  
OnCo record `ifosfamide` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Ifosfamide is an alkylating chemotherapy partnered with doxorubicin in sarcoma and with etoposide in Ewing sarcoma, given with a bladder-protecting drug.

## Summary

Ifosfamide is an alkylating prodrug activated by CYP2B6 and CYP3A4 to a mustard that crosslinks DNA; its chloroacetaldehyde metabolite causes the characteristic encephalopathy and nephrotoxicity, and mesna uroprotection is mandatory to prevent haemorrhagic cystitis. Approved in 1988 for germ cell testicular cancer, it is standard off-label as the partner of doxorubicin in AIM for soft-tissue sarcoma, in MAP-IE for osteosarcoma, and with etoposide in VDC/IE for Ewing sarcoma, the regimen established by INT-0091. Febrile neutropenia occurred in 46% of patients on the AIM arm of EORTC 62012, encephalopathy in about 10% (treated with methylene blue) and haemorrhagic cystitis in about 5% even with mesna. It is a powerful alkylator whose use depends on protecting the bladder, kidneys and brain from its by-products.

## Fields

- Kind: Treatment
- Status: approved
- Last checked: 2026-09-07
- Brand: Ifex
- Modality: Cytotoxic chemotherapy (alkylating agent)
- Mechanism: Prodrug activated by CYP2B6/3A4 to an alkylating mustard causing DNA crosslinks; chloroacetaldehyde metabolite causes neuro- and nephrotoxicity.
- Approvals: US 1988: Germ cell testicular cancer; widely used off-label in sarcoma
- Dosing: IV; 9-10 g/m2 per cycle over 3-5 days with mesna (sarcoma); 1.8 g/m2 × 5 days with etoposide (Ewing)
- Toxicity (grade 3+): Febrile neutropenia (with doxorubicin) 46%

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Ifosfamide
- FDA label (DailyMed): https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Ifosfamide

## Connected records

- drugs: [Mesna](https://onco.cc/drugs/mesna/)
- cancers: [Burkitt lymphoma](https://onco.cc/cancers/burkitt-lymphoma/), [Central nervous system germ cell tumours (germinoma and non-germinomatous)](https://onco.cc/cancers/cns-germ-cell-tumours/), [Childhood lung and airway tumours (pleuropulmonary blastoma, tracheobronchial tumours)](https://onco.cc/cancers/pleuropulmonary-blastoma/), [Chondrosarcoma](https://onco.cc/cancers/chondrosarcoma/), [Choriocarcinoma of the testis](https://onco.cc/cancers/testicular-choriocarcinoma/), [Desmoplastic small round cell tumour](https://onco.cc/cancers/desmoplastic-small-round-cell-tumour/), [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Enteropathy-associated T-cell lymphoma](https://onco.cc/cancers/enteropathy-associated-t-cell-lymphoma/), [Epithelioid sarcoma](https://onco.cc/cancers/epithelioid-sarcoma/), [Ewing sarcoma](https://onco.cc/cancers/ewing-sarcoma/), [Extragonadal germ cell tumour](https://onco.cc/cancers/extragonadal-germ-cell-tumour/), [Extranodal NK/T-cell lymphoma](https://onco.cc/cancers/extranodal-nk-t-cell-lymphoma/), [Germ cell tumours of childhood and adolescence (extracranial and CNS)](https://onco.cc/cancers/paediatric-germ-cell-tumours/), [Leiomyosarcoma](https://onco.cc/cancers/leiomyosarcoma/), [Malignant peripheral nerve sheath tumour (MPNST)](https://onco.cc/cancers/malignant-peripheral-nerve-sheath-tumour/), [Mediastinal germ cell tumour](https://onco.cc/cancers/mediastinal-germ-cell-tumour/), [Monomorphic epitheliotropic intestinal T-cell lymphoma](https://onco.cc/cancers/monomorphic-epitheliotropic-intestinal-t-cell-lymphoma/), [Myxofibrosarcoma](https://onco.cc/cancers/myxofibrosarcoma/), [Node-positive and metastatic penile cancer](https://onco.cc/cancers/node-positive-penile-cancer/), [NUT carcinoma (midline carcinoma with NUTM1 rearrangement)](https://onco.cc/cancers/nut-carcinoma/), [Osteosarcoma](https://onco.cc/cancers/osteosarcoma/), [Penile cancer](https://onco.cc/cancers/penile/), [Pleuropulmonary blastoma (types I, Ir, II and III)](https://onco.cc/cancers/pleuropulmonary-blastoma-dicer1/), [Relapsed and refractory classical Hodgkin lymphoma](https://onco.cc/cancers/relapsed-refractory-hodgkin-lymphoma/), [Retroperitoneal sarcoma](https://onco.cc/cancers/retroperitoneal-sarcoma/), [Rhabdomyosarcoma](https://onco.cc/cancers/rhabdomyosarcoma/), [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/), [Soft tissue sarcoma of the extremity (localised and advanced)](https://onco.cc/cancers/extremity-soft-tissue-sarcoma/), [Synovial sarcoma](https://onco.cc/cancers/synovial-sarcoma/), [Testicular germ cell tumours](https://onco.cc/cancers/testicular/), [Undifferentiated pleomorphic sarcoma (UPS)](https://onco.cc/cancers/undifferentiated-pleomorphic-sarcoma/), [Uterine carcinosarcoma](https://onco.cc/cancers/uterine-carcinosarcoma/), [Wilms tumour (nephroblastoma)](https://onco.cc/cancers/wilms-tumor/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [Fertility in boys and young men treated for cancer, including testicular tissue banking](https://onco.cc/technologies/rejuv-paed-fertility-male/), [Fertility in girls and young women treated for cancer, including ovarian tissue freezing](https://onco.cc/technologies/rejuv-paed-fertility-female/), [Kidneys after cisplatin, ifosfamide, radiotherapy and nephrectomy in childhood](https://onco.cc/technologies/rejuv-paed-kidneys/), [Teeth, jaws and facial growth after treatment in childhood](https://onco.cc/technologies/rejuv-paed-teeth-and-face/)
- trials: [A Eurosarc Study of Mifamurtide in Advanced Osteosarcoma (MEMOS)](https://onco.cc/trials/nct02441309/), [A Study to Evaluate Glofitamab Monotherapy and Glofitamab + Chemoimmunotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Matu](https://onco.cc/trials/nct05533775/), [A Trial to Learn How Effective and Safe Odronextamab is Compared to Standard of Care for Adult Participants With Previously Treated Aggressive B-cell ](https://onco.cc/trials/nct06230224/), [ACNS0122](https://onco.cc/trials/acns0122/), [ACNS1123](https://onco.cc/trials/acns1123/), [AEWS0031](https://onco.cc/trials/aews0031/), [Aldoxorubicin versus investigator's choice in relapsed or refractory soft tissue sarcoma](https://onco.cc/trials/aldoxorubicin-phase-3-sts/), [EORTC 62012](https://onco.cc/trials/eortc-62012/), [EURAMOS-1](https://onco.cc/trials/euramos-1/), [Euro Ewing 2012](https://onco.cc/trials/euro-ewing-2012/), [GETUG 13](https://onco.cc/trials/getug-13/), [High-Risk Neuroblastoma Study 2 of SIOP-Europa-Neuroblastoma (SIOPEN)](https://onco.cc/trials/nct04221035/), [InPACT](https://onco.cc/trials/inpact/), [INT-0091 (Ewing sarcoma)](https://onco.cc/trials/int-0091/), [International Collaborative Treatment Protocol For Children And Adolescents With Acute Lymphoblastic Leukemia](https://onco.cc/trials/nct01117441/), [ISG-STS 1001](https://onco.cc/trials/isg-sts-1001/), [MASCT-I Combined With Doxorubicin and Ifosfamide for First-line Treatment of Advanced Soft Tissue Sarcoma](https://onco.cc/trials/nct06277154/), [MATRix/IELSG43](https://onco.cc/trials/ielsg43/), [SMILE](https://onco.cc/trials/smile-enktl/), [Study of Pixantrone in CD20+ Relapsed/Refractory Aggressive Non-Hodgkin Lymphoma](https://onco.cc/trials/nct03458260/), [TIGER: standard-dose TIP versus high-dose TI-CE with stem cell transplant as first salvage for relapsed germ cell tumours](https://onco.cc/trials/tiger-trial/), [Treatment Protocol of the NHL-BFM and the NOPHO Study Groups for Mature Aggressive B-cell Lymphoma and Leukemia in Children and Adolescents](https://onco.cc/trials/nct03206671/)
- terms: [Fertility before lymphoma treatment: what to ask for, and when](https://onco.cc/terms/lymphoma-tx-fertility-preservation/), [FOXO1 fusion status and IRS group (rhabdomyosarcoma)](https://onco.cc/terms/foxo1-fusion-status/), [Histological response to induction chemotherapy (osteosarcoma and Ewing sarcoma)](https://onco.cc/terms/histological-response-induction/), [SS18::SSX fusion (synovial sarcoma)](https://onco.cc/terms/ss18-ssx-fusion/), [The lymphoma regimen alphabet: R-CHOP, pola-R-CHP, DA-EPOCH-R, ABVD, BEACOPP and the rest](https://onco.cc/terms/lymphoma-tx-regimen-alphabet/)
- key papers: [EORTC 62012: doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced soft tissue sarcoma](https://onco.cc/key-papers/paper-eortc-62012-doxorubicin-ifosfamide-judson-lancet-oncol-2014/), [GOG-0261: paclitaxel-carboplatin versus paclitaxel-ifosfamide in uterine carcinosarcoma](https://onco.cc/key-papers/paper-gog-0261-carcinosarcoma-powell-jco-2022/), [Neoadjuvant paclitaxel, ifosfamide and cisplatin (TIP) for penile cancer with bulky lymph node metastases](https://onco.cc/key-papers/paper-pagliaro-neoadjuvant-tip-penile-cancer-jco-2010/), [Phase II study of SMILE chemotherapy for newly diagnosed stage IV, relapsed, or refractory extranodal natural killer (NK)/T-cell lymphoma, nasal type: the NK-Cell Tumor Study Group study](https://onco.cc/key-papers/paper-smile-chemotherapy-nk-t-cell-lymphoma-jco-2011/)
- people: [Lance Armstrong](https://onco.cc/people/lance-armstrong/)

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