U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C7H15Cl2N2O2P
Molecular Weight 261.086
Optical Activity ( + / - )
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of IFOSFAMIDE

SMILES

ClCCNP1(=O)OCCCN1CCCl

InChI

InChIKey=HOMGKSMUEGBAAB-UHFFFAOYSA-N
InChI=1S/C7H15Cl2N2O2P/c8-2-4-10-14(12)11(6-3-9)5-1-7-13-14/h1-7H2,(H,10,12)

HIDE SMILES / InChI
Glufosamide (glucosylifosfamide mustars) consists of iphosphoramide mustard conjugated to glucose, and is an alkylating agent (affecting the ability of the cancer cell to multiply by causing breakage of the DNA strands). Glufosamide is considered a targeted chemotherapy with fewer side effects than alternative chemotherapies. Its specific mode of action on normal and pathological cells is still under investigation. Glufosamide was studied for use in several cancers, like pancreatic and prostate cancer, and head and neck squamous cell carcinoma. Multipe clinical trials have been completed or are still ongoing. Most promising results were found when glufosamide was used in combination treatments, rather than alone.

CNS Activity

Curator's Comment: Ifosfamide crosses the blood-brain barrier and may cause encephalopathy.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
IFEX

Approved Use

Ifosfamide injection, used in combination with certain other approved antineoplastic agents, is indicated for third line chemotherapy of germ cell testicular cancer. It should be used in combination with a prophylactic agent for hemorrhagic cystitis, such as mesna.

Launch Date

1988
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
200 μM
1.5 g/m² single, oral
dose: 1.5 g/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
IFOSFAMIDE blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
203 μM
1.5 g/m² single, intravenous
dose: 1.5 g/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered:
IFOSFAMIDE blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1360 μM × h
1.5 g/m² single, oral
dose: 1.5 g/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
IFOSFAMIDE blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
1520 μM × h
1.5 g/m² single, intravenous
dose: 1.5 g/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered:
IFOSFAMIDE blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
7.54 mM × h
3 g/m² 1 times / day multiple, intravenous
dose: 3 g/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
IFOSFAMIDE blood
Homo sapiens
population: UNHEALTHY
age: CHILD
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
5 h
1.5 g/m² single, oral
dose: 1.5 g/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
IFOSFAMIDE blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
5.6 h
1.5 g/m² single, intravenous
dose: 1.5 g/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered:
IFOSFAMIDE blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
2.12 h
3 g/m² 1 times / day multiple, intravenous
dose: 3 g/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
IFOSFAMIDE blood
Homo sapiens
population: UNHEALTHY
age: CHILD
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
100%
IFOSFAMIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
18 g/m2 1 times / day multiple, intravenous (total)
MTD
Dose: 18 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 18 g/m2, 1 times / day
Sources: Page: p.1090
unhealthy, 45
n = 6
Health Status: unhealthy
Condition: Sarcoma
Age Group: 45
Sex: M+F
Population Size: 6
Sources: Page: p.1090
DLT: Neutropenia, Infection...
Dose limiting toxicities:
Neutropenia (grade 4, 83.3%)
Infection (severe, 33.3%)
Thrombocytopenia (grade 4, 66.7%)
Sources: Page: p.1090
2.25 g/m2 1 times / day multiple, intravenous
MTD
Dose: 2.25 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 2.25 g/m2, 1 times / day
Co-administed with::
doxorubicin, i.v(45 mg/m2)
Sources: Page: p.6
unhealthy, 45
n = 3
Health Status: unhealthy
Condition: Breast cancer
Age Group: 45
Sex: F
Population Size: 3
Sources: Page: p.6
DLT: Neutropenia, Febrile neutropenia...
Dose limiting toxicities:
Neutropenia (grade 4, 66.7%)
Febrile neutropenia (grade 5, 33.3%)
Thrombocytopenia (grade 4, 66.7%)
Anemia (grade 4, 66.7%)
Sources: Page: p.6
1.2 g/m2 1 times / day multiple, intravenous
Recommended
Dose: 1.2 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 1.2 g/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Testicular cancer
Sources: Page: p.1
Disc. AE: Nephrotoxicity, Renal failure...
AEs leading to
discontinuation/dose reduction:
Nephrotoxicity (severe)
Renal failure (severe)
Cystitis hemorrhagic (severe)
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
Thrombocytopenia grade 4, 66.7%
DLT
18 g/m2 1 times / day multiple, intravenous (total)
MTD
Dose: 18 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 18 g/m2, 1 times / day
Sources: Page: p.1090
unhealthy, 45
n = 6
Health Status: unhealthy
Condition: Sarcoma
Age Group: 45
Sex: M+F
Population Size: 6
Sources: Page: p.1090
Neutropenia grade 4, 83.3%
DLT
18 g/m2 1 times / day multiple, intravenous (total)
MTD
Dose: 18 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 18 g/m2, 1 times / day
Sources: Page: p.1090
unhealthy, 45
n = 6
Health Status: unhealthy
Condition: Sarcoma
Age Group: 45
Sex: M+F
Population Size: 6
Sources: Page: p.1090
Infection severe, 33.3%
DLT
18 g/m2 1 times / day multiple, intravenous (total)
MTD
Dose: 18 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 18 g/m2, 1 times / day
Sources: Page: p.1090
unhealthy, 45
n = 6
Health Status: unhealthy
Condition: Sarcoma
Age Group: 45
Sex: M+F
Population Size: 6
Sources: Page: p.1090
Anemia grade 4, 66.7%
DLT
2.25 g/m2 1 times / day multiple, intravenous
MTD
Dose: 2.25 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 2.25 g/m2, 1 times / day
Co-administed with::
doxorubicin, i.v(45 mg/m2)
Sources: Page: p.6
unhealthy, 45
n = 3
Health Status: unhealthy
Condition: Breast cancer
Age Group: 45
Sex: F
Population Size: 3
Sources: Page: p.6
Neutropenia grade 4, 66.7%
DLT
2.25 g/m2 1 times / day multiple, intravenous
MTD
Dose: 2.25 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 2.25 g/m2, 1 times / day
Co-administed with::
doxorubicin, i.v(45 mg/m2)
Sources: Page: p.6
unhealthy, 45
n = 3
Health Status: unhealthy
Condition: Breast cancer
Age Group: 45
Sex: F
Population Size: 3
Sources: Page: p.6
Thrombocytopenia grade 4, 66.7%
DLT
2.25 g/m2 1 times / day multiple, intravenous
MTD
Dose: 2.25 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 2.25 g/m2, 1 times / day
Co-administed with::
doxorubicin, i.v(45 mg/m2)
Sources: Page: p.6
unhealthy, 45
n = 3
Health Status: unhealthy
Condition: Breast cancer
Age Group: 45
Sex: F
Population Size: 3
Sources: Page: p.6
Febrile neutropenia grade 5, 33.3%
DLT, Disc. AE
2.25 g/m2 1 times / day multiple, intravenous
MTD
Dose: 2.25 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 2.25 g/m2, 1 times / day
Co-administed with::
doxorubicin, i.v(45 mg/m2)
Sources: Page: p.6
unhealthy, 45
n = 3
Health Status: unhealthy
Condition: Breast cancer
Age Group: 45
Sex: F
Population Size: 3
Sources: Page: p.6
Cystitis hemorrhagic severe
Disc. AE
1.2 g/m2 1 times / day multiple, intravenous
Recommended
Dose: 1.2 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 1.2 g/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Testicular cancer
Sources: Page: p.1
Nephrotoxicity severe
Disc. AE
1.2 g/m2 1 times / day multiple, intravenous
Recommended
Dose: 1.2 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 1.2 g/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Testicular cancer
Sources: Page: p.1
Renal failure severe
Disc. AE
1.2 g/m2 1 times / day multiple, intravenous
Recommended
Dose: 1.2 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 1.2 g/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Testicular cancer
Sources: Page: p.1
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes
yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
no
no
poor
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
no (co-administration study)
Comment: Coadministration of ifosfamide with ketoconazole or rifampin did not produce changes inthe pharmacokinetics of the parent or metabolites that may result in an increased benefit of ifosfamidetherapy. (https://pubmed.ncbi.nlm.nih.gov/11503007/)
Page: 28.0
yes
no (co-administration study)
Comment: Coadministration of ifosfamide with ketoconazole or rifampin did not produce changes inthe pharmacokinetics of the parent or metabolites that may result in an increased benefit of ifosfamidetherapy. (https://pubmed.ncbi.nlm.nih.gov/11503007/)
Page: 28.0
PubMed

PubMed

TitleDatePubMed
Vinorelbine-based regimens as salvage treatment in patients with advanced non-small cell lung cancer: two parallel multicenter phase II trials.
2001
A phase II study of weekly alternating chemotherapy in extensive-stage small cell lung cancer.
2001
The efficacy of combination chemotherapy including intraperitoneal cisplatinum and mitoxantrone with intravenous ifosfamide in patients with FIGO stage I C ovarian carcinoma.
2001
Malignant mixed mullerian tumor of the ovary: report of four cases.
2001
Treatment of ruptured undifferentiated sarcoma of the liver in children: a report of two cases and review of the literature.
2001
Carnitine protects mitochondria and removes toxic acyls from xenobiotics.
2001
Paclitaxel by 72-hour continuous infusion followed by bolus intravenous ifosfamide or epirubicin: results of two phase I studies.
2001
Comparison of double and triple high-dose chemotherapy with autologous blood stem cell transplantation in patients with metastatic breast cancer.
2001
Salvage chemotherapy in relapsed germ cell tumors.
2001 Apr
Treatment of patients with metastatic germ cell tumors relapsing after high-dose chemotherapy.
2001 Apr
[Post-operative neoadjuvant chemotherapy before radiotherapy as compared to immediate radiotherapy followed by maintenance chemotherapy in the treatment of medulloblastoma in childhood: results of German prospective randomised trial HIT'91].
2001 Apr
[Pigmented villonodular synovitis: apropos of 3 cases].
2001 Apr
A three-drug regimen (gemcitabine, ifosfamide and cisplatin) for advanced non-small-cell lung cancer.
2001 Apr
Modified dorsalis pedis flap for coverage of a pretibial pressure sore after hip rotationplasty.
2001 Apr
Local hyperthermia, radiation, and chemotherapy in recurrent breast cancer is feasible and effective except for inflammatory disease.
2001 Apr 1
Phase II study of paclitaxel, ifosfamide, and carboplatin in patients with recurrent or metastatic head and neck squamous cell carcinoma.
2001 Apr 1
The current status of docetaxel for advanced non-small cell lung cancer.
2001 Feb
Phase II study of a high-dose ifosfamide-based chemotherapy regimen with growth factor rescue in recurrent aggressive NHL. High response rates and limited toxicity, but limited impact on long-term survival.
2001 Feb
Sustained response of sarcomatoid renal-cell carcinoma to MAID chemotherapy: case report and review of the literature.
2001 Feb
Chemotherapy agents in transitional cell carcinoma: the old and the new.
2001 Feb
A comparison of methods of loco-regional chemotherapy combined with systemic chemotherapy as neo-adjuvant treatment of osteosarcoma of the extremity.
2001 Feb
Neoadjuvant chemotherapy for high grade osteosarcoma of the extremities: long-term results for patients treated according to the Rizzoli IOR/OS-3b protocol.
2001 Feb
Absence of major peripheral neuropathy in a phase II trial of ifosfamide with vinorelbine in patients with ovarian cancer previously treated with platinum and paclitaxel.
2001 Feb
[Addisonian crisis as first manifestation of adrenal gland insufficiency in patient diagnosed with lung cancer].
2001 Jan
[Prostatic angiosarcoma: report of a new case].
2001 Jan
Long-term stent implantation in a case of relapsing intrathoracic Ewing-sarcoma.
2001 Jan 15
A randomised phase II study on neo-adjuvant chemotherapy for 'high-risk' adult soft-tissue sarcoma.
2001 Jun
Importance of surgery as salvage treatment after high dose chemotherapy failure in germ cell tumors.
2001 Jun
A preclinical model for experimental chemotherapy of human head and neck cancer.
2001 Jun
High-dose melphalan, etoposide, total-body irradiation, and autologous stem-cell reconstitution as consolidation therapy for high-risk Ewing's sarcoma does not improve prognosis.
2001 Jun 1
Immunoglobulin D myeloma presenting as an extraosseous soft tissue tumor.
2001 Mar
[Surgical treatment of non-small cell lung cancer with mediastinal node invasion. A retrospective study].
2001 Mar
Necrotic, rather than apoptotic, cell death caused by cytochrome P450-activated ifosfamide.
2001 Mar
Primary breast tumor levels of suspected molecular determinants of cellular sensitivity to cyclophosphamide, ifosfamide, and certain other anticancer agents as predictors of paired metastatic tumor levels of these determinants. Rational individualization of cancer chemotherapeutic regimens.
2001 Mar
A phase II study of dose-intense ifosfamide plus epirubicin with hematopoietic growth factors for the treatment of patients with advanced soft tissue sarcomas; a novel sequential schedule.
2001 Mar
Gemcitabine for the treatment of non-small-cell lung cancer.
2001 Mar
Ifosfamide and mitoxantrone in the treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck.
2001 Mar
Intrasellar rhabdomyosarcoma: case report.
2001 Mar
[A case of primary malignant hemangiopericytoma of the lung with marked response to combination chemotherapy with cisplatin, ifosfamide and gemcitabine].
2001 Mar
Phase I trial of ifosfamide and 24-h infusional paclitaxel in pelvic malignancies: a Gynecologic Oncology Group study.
2001 Mar
Metastatic osteosarcoma to the liver after treatment for synovial sarcoma: a case report.
2001 Mar
Adjuvant chemotherapy for adult soft tissue sarcomas of the extremities and girdles: results of the Italian randomized cooperative trial.
2001 Mar 1
Localized Ewing tumor of bone: final results of the cooperative Ewing's Sarcoma Study CESS 86.
2001 Mar 15
Tumor oxygenation after radiotherapy, chemotherapy, and/or hyperthermia predicts tumor free survival.
2001 Mar 15
Histologic response of high-grade nonmetastatic osteosarcoma of the extremity to chemotherapy,
2001 May
Gemcitabine and vinorelbine as second-line therapy in non-small-cell lung cancer after prior treatment with taxane+platinum-based regimens.
2001 May
Haemoperfusion combined with haemodialysis in ifosfamide intoxication.
2001 May
Topoisomerase IIalpha and other drug resistance markers in advanced non-small cell lung cancer.
2001 May
Outcomes of treatment of children and adolescents with recurrent non-Hodgkin's lymphoma and Hodgkin's disease with dexamethasone, etoposide, cisplatin, cytarabine, and l-asparaginase, maintenance chemotherapy, and transplantation: Children's Cancer Group Study CCG-5912.
2001 May 1
Microencapsulated cell-mediated treatment of inoperable pancreatic carcinoma.
2001 May 19
Patents

Sample Use Guides

30-min infusion at a dose of 1.2 grams per m2 per day for 5 consecutive days
Route of Administration: Intravenous
Human testicular germ cell tumour lines H 12.1 and 2102 EP were treated with ifosfamide at 50 mg kg-1 day-1.
Name Type Language
IFOSFAMIDE
EP   HSDB   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
INN   USAN  
Official Name English
Z4942
Code English
2H-1,3,2-OXAZAPHOSPHORIN-2-AMINE, N,3-BIS(2-CHLOROETHYL)TETRAHYDRO-, 2-OXIDE
Systematic Name English
NSC-109724
Code English
ISOCYCLOPHOSPHAMIDE
Common Name English
3-(2-Chloroethyl)-2-[(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide
Systematic Name English
IFOSFAMIDE [USP-RS]
Common Name English
ifosfamide [INN]
Common Name English
IFOSFAMIDE [USAN]
Common Name English
IFOSFAMIDE [USP MONOGRAPH]
Common Name English
IFOSFAMIDE [EP IMPURITY]
Common Name English
MJF 9325
Code English
IFOSFAMIDE [MART.]
Common Name English
MJF-9325
Code English
IFOSFAMIDE [JAN]
Common Name English
Ifosfamide [WHO-DD]
Common Name English
Z-4942
Code English
IFOSFAMIDE [MI]
Common Name English
N,3-BIS(2-CHLOROETHYL)TETRAHYDRO-2H-1,3,2-OXAZAPHOSPHORIN-2-AMINE 2-OXIDE
Systematic Name English
IFOSFAMIDE [EP MONOGRAPH]
Common Name English
IFOSFAMIDE [HSDB]
Common Name English
ISOPHOSPHAMIDE [IARC]
Common Name English
IFOSFAMIDE [ORANGE BOOK]
Common Name English
IFOSFAMIDE [VANDF]
Common Name English
IFEX
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C697
Created by admin on Sat Dec 16 17:57:03 GMT 2023 , Edited by admin on Sat Dec 16 17:57:03 GMT 2023
WHO-VATC QL01AA06
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WHO-ATC L01AA06
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FDA ORPHAN DRUG 17786
Created by admin on Sat Dec 16 17:57:03 GMT 2023 , Edited by admin on Sat Dec 16 17:57:03 GMT 2023
NDF-RT N0000175558
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WHO-ESSENTIAL MEDICINES LIST 8.2
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NDF-RT N0000000236
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LIVERTOX NBK548567
Created by admin on Sat Dec 16 17:57:03 GMT 2023 , Edited by admin on Sat Dec 16 17:57:03 GMT 2023
FDA ORPHAN DRUG 8585
Created by admin on Sat Dec 16 17:57:03 GMT 2023 , Edited by admin on Sat Dec 16 17:57:03 GMT 2023
Code System Code Type Description
PUBCHEM
3690
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PRIMARY
IUPHAR
7201
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PRIMARY
EVMPD
SUB08125MIG
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PRIMARY
DRUG BANK
DB01181
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PRIMARY
DRUG CENTRAL
1421
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PRIMARY
SMS_ID
100000083681
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PRIMARY
CAS
3778-73-2
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PRIMARY
FDA UNII
UM20QQM95Y
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PRIMARY
NCI_THESAURUS
C564
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PRIMARY
RS_ITEM_NUM
1336205
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PRIMARY
NSC
109724
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PRIMARY
CHEBI
5864
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PRIMARY
EPA CompTox
DTXSID7020760
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PRIMARY
INN
2865
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PRIMARY
WIKIPEDIA
IFOSFAMIDE
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PRIMARY
MERCK INDEX
m6207
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PRIMARY Merck Index
RXCUI
5657
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PRIMARY RxNorm
MESH
D007069
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PRIMARY
LACTMED
Ifosfamide
Created by admin on Sat Dec 16 17:57:03 GMT 2023 , Edited by admin on Sat Dec 16 17:57:03 GMT 2023
PRIMARY
ECHA (EC/EINECS)
223-237-3
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PRIMARY
HSDB
7023
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PRIMARY
ChEMBL
CHEMBL1024
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PRIMARY
DAILYMED
UM20QQM95Y
Created by admin on Sat Dec 16 17:57:03 GMT 2023 , Edited by admin on Sat Dec 16 17:57:03 GMT 2023
PRIMARY