RALTITREXED DISODIUM

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H20N4O6S.2Na
Molecular Weight	502.451
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].[Na+].CN(CC1=CC2=C(C=C1)N=C(C)NC2=O)C3=CC=C(S3)C(=O)N[C@@H](CCC([O-])=O)C([O-])=O

InChI

InChIKey=HYYVJHYAMGPPLX-CKUXDGONSA-L

InChI=1S/C21H22N4O6S.2Na/c1-11-22-14-4-3-12(9-13(14)19(28)23-11)10-25(2)17-7-6-16(32-17)20(29)24-15(21(30)31)5-8-18(26)27;;/h3-4,6-7,9,15H,5,8,10H2,1-2H3,(H,24,29)(H,26,27)(H,30,31)(H,22,23,28);;/q;2*+1/p-2/t15-;;/m0../s1

HIDE SMILES / InChI

Molecular Formula	C21H20N4O6S
Molecular Weight	456.472
Charge	-2
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	Na
Molecular Weight	22.9898
Charge	1
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.drugbank.ca/drugs/DB00293
Curator's Comment: Description was created based on several sources, including https://www.medicines.org.uk/emc/medicine/2307 https://www.ncbi.nlm.nih.gov/pubmed/21148615

Raltitrexed belongs to a group of medicines known as antimetabolites. It is used to treat cancer of the colon and rectum. It may also be used to treat other kinds of cancer, as determined by your doctor. Raltitrexed blocks an enzyme needed by the cell to live. This interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by raltitrexed, other effects will also occur. Some of these may be serious and must be reported to your doctor. Other effects, like hair loss, may not be serious but may cause concern. Raltitrexed inhibits thymidylate synthase (TS) leading to DNA fragmentation and cell death. It is transported into cells via a reduced folate carrier. Inside the cell Raltitrexed is extensively polyglutamated, which enhances thymidylate synthase inhibitory power and duration. Inhibition of this enzyme results in decreased synthesis of thymidine triphosphate which is required for DNA synthesis. Raltitrexed is used for the treatment of malignant neoplasm of colon and rectum. Although raltitrexed is not approved by the US FDA, the drug was licensed in Canada and some European countries.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Thymidylate synthase 32 Target ID: CHEMBL1952 Sources: https://www.drugbank.ca/drugs/DB00293	Inhibitor 8297		530.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Advanced colorectal cancer 8 Sources: http://www.bccancer.bc.ca/drug-database-site/Drug%20Index/Raltitrexed_monograph_1June2013_formatted.pdf	Palliative		Approved 8429	Tomudex Approved Use The palliative treatment of advanced colorectal cancer where 5-Fluorouracil and folinic acid based regimens are either not tolerated or inappropriate. Launch Date 2000

C_max

Value	Dose	Co-administered	Analyte	Population
567.1 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9820178	3 mg/m² 1 times / day other, intravenous dose: 3 mg/m² route of administration: Intravenous experiment type: OTHER co-administered:		RALTITREXED blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
736.8 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9619761	3 mg/m² single, intravenous dose: 3 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		RALTITREXED plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1547.9 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9820178	3 mg/m² 1 times / day other, intravenous dose: 3 mg/m² route of administration: Intravenous experiment type: OTHER co-administered:		RALTITREXED blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2341.7 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9619761	3 mg/m² single, intravenous dose: 3 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		RALTITREXED plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.82 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9820178	3 mg/m² 1 times / day other, intravenous dose: 3 mg/m² route of administration: Intravenous experiment type: OTHER co-administered:		RALTITREXED blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
12 min EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9619761	3 mg/m² single, intravenous dose: 3 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		RALTITREXED plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
7% OTHER GOV https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf			RALTITREXED plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
4.5 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose\|MTD Dose: 4.5 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 4.5 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/	unhealthy, Median age 55.5 years n = 9 Health Status: unhealthy Condition: solid tumors Age Group: Median age 55.5 years Sex: M+F Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/	DLT: Asthenia, Granulocytopenia... Other AEs: Leukocytopenia, Nausea... Dose limiting toxicities: Asthenia (grade 3, 33.3%) Granulocytopenia (grade 4, 11.1%) Fatigue (grade 3, 11.1%) Other AEs: Leukocytopenia (grade 3, 11.1%) Nausea (grade 3, 11.1%) Aspartate aminotransferase increased (grade 3, 11.1%) Alanine aminotransferase increase (grade 3, 33.3%) Bilirubin elevated (grade 3-4, 11.1%) Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/
3.5 mg/m2 1 times / 3 weeks multiple, intravenous Studied dose Dose: 3.5 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 3.5 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/	unhealthy, Median age 55.5 years n = 13 Health Status: unhealthy Condition: solid tumors Age Group: Median age 55.5 years Sex: M+F Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/	DLT: Asthenia... Other AEs: Decreased hemoglobin... Dose limiting toxicities: Asthenia (grade 3, 15.4%) Other AEs: Decreased hemoglobin (grade 3, 7.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/
4 mg/m2 1 times / 3 weeks multiple, intravenous Studied dose Dose: 4 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 4 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/	unhealthy, Median age 55.5 years n = 12 Health Status: unhealthy Condition: solid tumors Age Group: Median age 55.5 years Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/	DLT: Granulocytopenia, Bilirubin elevated... Dose limiting toxicities: Granulocytopenia (grade 4, 16.7%) Bilirubin elevated (grade 4, 8.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/
2.5 mg/m2 1 times / 3 weeks multiple, intravenous Studied dose Dose: 2.5 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 2.5 mg/m2, 1 times / 3 weeks Co-administed with:: 5-iodo-2'-deoxyuridine(10400 mg/m2 IV; every 3 weeks) Sources: https://pubmed.ncbi.nlm.nih.gov/11432631/	unhealthy, Median age 62 years n = 3 Health Status: unhealthy Condition: Colorectal Cancer Age Group: Median age 62 years Sex: M+F Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/11432631/	DLT: Neutropenia... Dose limiting toxicities: Neutropenia (grade 4, 66.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/11432631/
3 mg/m2 1 times / 3 weeks multiple, intravenous Studied dose Dose: 3 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 3 mg/m2, 1 times / 3 weeks Sources: http://www.bccancer.bc.ca/drug-database-site/Drug%20Index/Raltitrexed_monograph_1June2013_formatted.pdf https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf	unhealthy n = 861 Health Status: unhealthy Condition: Colorectal Cancer Sex: M+F Population Size: 861 Sources: http://www.bccancer.bc.ca/drug-database-site/Drug%20Index/Raltitrexed_monograph_1June2013_formatted.pdf https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf	DLT: Leukocytopenia, Transaminases increased... Dose limiting toxicities: Leukocytopenia (grade 3-4, 12.9%) Transaminases increased (grade 3-4, 10.1%) Sources: http://www.bccancer.bc.ca/drug-database-site/Drug%20Index/Raltitrexed_monograph_1June2013_formatted.pdf https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf
3 mg/m2 1 times / 3 weeks multiple, intravenous Studied dose Dose: 3 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 3 mg/m2, 1 times / 3 weeks Sources: https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf Page: 201710/TOMUDEX_PM.pdf - p.9	unhealthy n = 861 Health Status: unhealthy Condition: Colorectal Cancer Sex: M+F Population Size: 861 Sources: https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf Page: 201710/TOMUDEX_PM.pdf - p.9	Other AEs: Nausea and vomiting, Diarrhea... Other AEs: Nausea and vomiting (grade 3-4, 11.6%) Diarrhea (grade 3-4, 11.1%) Constipation (grade 3-4, 2%) Oral soft tissue conditions (grade 3-4, 2.1%) Pain (grade 3-4, 7.3%) Infection (grade 3-4, 5%) Hemoglobin decreased (grade 3-4, 6.5%) Thrombocytopenia (grade 3-4, 3.5%) Blood bilirubin decreased (grade 3-4, 2.2%) Sources: https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf Page: 201710/TOMUDEX_PM.pdf - p.9

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BSEP 402 MRP4 204 MRP3 157 MRP1 106	MRP4 77 OATP1A4 2

Drug as perpetrator

Target	Modality	Activity
BSEP 403	inhibitor 3277 Sources: https://academic.oup.com/toxsci/article/136/1/216/1653420 Page: -	no [IC50 133 uM]
MRP1 172	inhibitor 3277 Sources: https://academic.oup.com/toxsci/article/136/1/216/1653420 Page: -	no [IC50 133 uM]
MRP3 207	inhibitor 3277 Sources: https://academic.oup.com/toxsci/article/136/1/216/1653420 Page: -	no [IC50 133 uM]
MRP4 238	inhibitor 3277 Sources: https://academic.oup.com/toxsci/article/136/1/216/1653420 Page: -	no [IC50 133 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
MRP4 77	substrate 3367 Sources: https://www.sciencedirect.com/science/article/abs/pii/S0022354917302769 Page: -	yes [Km 43.7 uM]
OATP1A4 2	substrate 3367 Sources: https://www.sciencedirect.com/science/article/abs/pii/S0022354917302769 Page: -	yes

PubMed

Title	Date	PubMed
Phase I study of mitoxantrone, raltitrexed, levofolinic acid and 5-fluorouracil in advanced solid tumours.	2001	11269736
[Assessment of the cost of first line chemotherapy in metastatic colorectal cancer. Preliminary results in the FFCD 9601 trial].	2001 Aug-Sep	11598535
Synergistic efficacy of 3n-butyrate and 5-fluorouracil in human colorectal cancer xenografts via modulation of DNA synthesis.	2001 Mar	11231942
New therapies, new directions: advances in the systemic treatment of metastatic colorectal cancer.	2001 May	11905784
Second-line treatment with oxaliplatin + raltitrexed in patients with advanced colorectal cancer failing fluoropyrimidine/leucovorin-based chemotherapy.	2001 May	11432632
Preoperative chemoradiation with raltitrexed ('Tomudex') for T2/N+ and T3/N+ rectal cancers: a phase I study.	2001 Nov	11597383
[Colorectal cancer: irinotecan in combination with newer drugs].	2001 Nov-Dec	11995705
Multicenter phase II trial of dose-fractionated irinotecan in patients with advanced colorectal cancer failing oxaliplatin-based first-line combination chemotherapy.	2001 Sep	11697839
Present indications for adjuvant therapy in resectable rectal cancer.	2001 Sep-Oct	11975405
[Raltitrexed and oxaliplatin in colorectal cancer: in vitro and in vivo study of a synergistic cytostatic combination].	2002	12424937
Conjoint analysis of a new Chemotherapy: willingness to pay and preference for the features of raltitrexed versus standard therapy in advanced Colorectal Cancer.	2002	12201796
Multicenter phase I study of irinotecan plus raltitrexed in patients with 5-fluorouracil-refractory advanced colorectal cancer.	2002	12187070
Multicenter non-randomized phase II study of raltitrexed (Tomudex) and oxaliplatin in non-pretreated metastatic colorectal cancer patients.	2002 Jul	12176786
A rationale for the clinical development of the thymidylate synthase inhibitor ZD9331 in ovarian and other solid tumours.	2002 Jul 18	12084463
Advanced colorectal cancer treatment in Europe: what have we achieved?	2002 Jun	12045457
Raltitrexed in the treatment of elderly patients with advanced colorectal cancer: an active and low toxicity regimen.	2002 Jun	12044507
Oxaliplatin plus raltitrexed and leucovorin-modulated 5-fluorouracil i.v. bolus: a salvage regimen for colorectal cancer patients.	2002 Jun 17	12085178
Why hasn't the National Institute been 'NICE' to patients with colorectal cancer? National Institute of Clinical Excellence.	2002 Jun 5	12087447
Sequence-dependent effects of ZD1839 ('Iressa') in combination with cytotoxic treatment in human head and neck cancer.	2002 Mar 4	11875748
Phase I and pharmacokinetic study of irinotecan in combination with raltitrexed.	2002 Oct	12357298
Raltitrexed treatment promotes systemic inflammatory reaction in patients with colorectal carcinoma.	2002 Sep 9	12237767

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose is 3 mg/m2 given intravenously, as a single short, intravenous infusion in 50 to 250 ml of either 0.9% sodium chloride solution or 5% dextrose (glucose) solution. It is recommended that the infusion is given over a 15 minute period. Other drugs should not be mixed with 'Tomudex' (raltitrexed) in the same infusion container. In the absence of toxicity, treatment may be repeated every 3 weeks. Dose escalation above 3 mg/m2 is not recommended, since higher doses have been associated with an increased incidence of life-threatening or fatal toxicity.

Route of Administration: Intravenous

In Vitro Use Guide

In WiDr colon adenocarcinoma cells the cytotoxicity of 1.0 uM Raltitrexed (4 h) varied from 0% to >99% within the reported range of human serum thymidine concentrations from 500 to <50 nM, respectively.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 08:22:55 GMT 2023` Edited by `admin` on `Sat Dec 16 08:22:55 GMT 2023`
Record UNII	50VZN4BPUK
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

RALTITREXED DISODIUM

Common Name

English

Raltitrexed disodium [WHO-DD]

Common Name

English

L-GLUTAMIC ACID, N-((5-(((3,4-DIHYDRO-2-METHYL-4-OXO-6-QUINAZOLINYL)METHYL)METHYLAMINO)-2-THIENYL)CARBONYL)-, DISODIUM SALT

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2021

Created by admin on Sat Dec 16 08:22:55 GMT 2023 , Edited by admin on Sat Dec 16 08:22:55 GMT 2023

Code System Code Type Description

PUBCHEM

135565658

Created by admin on Sat Dec 16 08:22:55 GMT 2023 , Edited by admin on Sat Dec 16 08:22:55 GMT 2023

PRIMARY

NCI_THESAURUS

C148170

Created by admin on Sat Dec 16 08:22:55 GMT 2023 , Edited by admin on Sat Dec 16 08:22:55 GMT 2023

PRIMARY

FDA UNII

50VZN4BPUK

Created by admin on Sat Dec 16 08:22:55 GMT 2023 , Edited by admin on Sat Dec 16 08:22:55 GMT 2023

PRIMARY

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					FCB9EGG971

RALTITREXED

PARENT -> SALT/SOLVATE

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					FCB9EGG971

RALTITREXED

ACTIVE MOIETY

AE	Significance	Dose	Population
Aspartate aminotransferase increased	grade 3, 11.1%	4.5 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose\|MTD Dose: 4.5 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 4.5 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/	unhealthy, Median age 55.5 years n = 9 Health Status: unhealthy Condition: solid tumors Age Group: Median age 55.5 years Sex: M+F Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/
Leukocytopenia	grade 3, 11.1%	4.5 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose\|MTD Dose: 4.5 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 4.5 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/	unhealthy, Median age 55.5 years n = 9 Health Status: unhealthy Condition: solid tumors Age Group: Median age 55.5 years Sex: M+F Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/
Nausea	grade 3, 11.1%	4.5 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose\|MTD Dose: 4.5 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 4.5 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/	unhealthy, Median age 55.5 years n = 9 Health Status: unhealthy Condition: solid tumors Age Group: Median age 55.5 years Sex: M+F Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/
Fatigue	grade 3, 11.1% DLT	4.5 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose\|MTD Dose: 4.5 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 4.5 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/	unhealthy, Median age 55.5 years n = 9 Health Status: unhealthy Condition: solid tumors Age Group: Median age 55.5 years Sex: M+F Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/
Alanine aminotransferase increase	grade 3, 33.3%	4.5 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose\|MTD Dose: 4.5 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 4.5 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/	unhealthy, Median age 55.5 years n = 9 Health Status: unhealthy Condition: solid tumors Age Group: Median age 55.5 years Sex: M+F Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/
Asthenia	grade 3, 33.3% DLT	4.5 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose\|MTD Dose: 4.5 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 4.5 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/	unhealthy, Median age 55.5 years n = 9 Health Status: unhealthy Condition: solid tumors Age Group: Median age 55.5 years Sex: M+F Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/
Bilirubin elevated	grade 3-4, 11.1%	4.5 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose\|MTD Dose: 4.5 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 4.5 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/	unhealthy, Median age 55.5 years n = 9 Health Status: unhealthy Condition: solid tumors Age Group: Median age 55.5 years Sex: M+F Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/
Granulocytopenia	grade 4, 11.1% DLT	4.5 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose\|MTD Dose: 4.5 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 4.5 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/	unhealthy, Median age 55.5 years n = 9 Health Status: unhealthy Condition: solid tumors Age Group: Median age 55.5 years Sex: M+F Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/
Asthenia	grade 3, 15.4% DLT	3.5 mg/m2 1 times / 3 weeks multiple, intravenous Studied dose Dose: 3.5 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 3.5 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/	unhealthy, Median age 55.5 years n = 13 Health Status: unhealthy Condition: solid tumors Age Group: Median age 55.5 years Sex: M+F Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/
Decreased hemoglobin	grade 3, 7.7%	3.5 mg/m2 1 times / 3 weeks multiple, intravenous Studied dose Dose: 3.5 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 3.5 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/	unhealthy, Median age 55.5 years n = 13 Health Status: unhealthy Condition: solid tumors Age Group: Median age 55.5 years Sex: M+F Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/
Granulocytopenia	grade 4, 16.7% DLT	4 mg/m2 1 times / 3 weeks multiple, intravenous Studied dose Dose: 4 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 4 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/	unhealthy, Median age 55.5 years n = 12 Health Status: unhealthy Condition: solid tumors Age Group: Median age 55.5 years Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/
Bilirubin elevated	grade 4, 8.3% DLT	4 mg/m2 1 times / 3 weeks multiple, intravenous Studied dose Dose: 4 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 4 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/	unhealthy, Median age 55.5 years n = 12 Health Status: unhealthy Condition: solid tumors Age Group: Median age 55.5 years Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/10499608/ https://pubmed.ncbi.nlm.nih.gov/11432631/
Neutropenia	grade 4, 66.7% DLT	2.5 mg/m2 1 times / 3 weeks multiple, intravenous Studied dose Dose: 2.5 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 2.5 mg/m2, 1 times / 3 weeks Co-administed with:: 5-iodo-2'-deoxyuridine(10400 mg/m2 IV; every 3 weeks) Sources: https://pubmed.ncbi.nlm.nih.gov/11432631/	unhealthy, Median age 62 years n = 3 Health Status: unhealthy Condition: Colorectal Cancer Age Group: Median age 62 years Sex: M+F Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/11432631/
Transaminases increased	grade 3-4, 10.1% DLT	3 mg/m2 1 times / 3 weeks multiple, intravenous Studied dose Dose: 3 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 3 mg/m2, 1 times / 3 weeks Sources: http://www.bccancer.bc.ca/drug-database-site/Drug%20Index/Raltitrexed_monograph_1June2013_formatted.pdf https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf	unhealthy n = 861 Health Status: unhealthy Condition: Colorectal Cancer Sex: M+F Population Size: 861 Sources: http://www.bccancer.bc.ca/drug-database-site/Drug%20Index/Raltitrexed_monograph_1June2013_formatted.pdf https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf
Leukocytopenia	grade 3-4, 12.9% DLT	3 mg/m2 1 times / 3 weeks multiple, intravenous Studied dose Dose: 3 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 3 mg/m2, 1 times / 3 weeks Sources: http://www.bccancer.bc.ca/drug-database-site/Drug%20Index/Raltitrexed_monograph_1June2013_formatted.pdf https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf	unhealthy n = 861 Health Status: unhealthy Condition: Colorectal Cancer Sex: M+F Population Size: 861 Sources: http://www.bccancer.bc.ca/drug-database-site/Drug%20Index/Raltitrexed_monograph_1June2013_formatted.pdf https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf
Diarrhea	grade 3-4, 11.1%	3 mg/m2 1 times / 3 weeks multiple, intravenous Studied dose Dose: 3 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 3 mg/m2, 1 times / 3 weeks Sources: https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf Page: 201710/TOMUDEX_PM.pdf - p.9	unhealthy n = 861 Health Status: unhealthy Condition: Colorectal Cancer Sex: M+F Population Size: 861 Sources: https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf Page: 201710/TOMUDEX_PM.pdf - p.9
Nausea and vomiting	grade 3-4, 11.6%	3 mg/m2 1 times / 3 weeks multiple, intravenous Studied dose Dose: 3 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 3 mg/m2, 1 times / 3 weeks Sources: https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf Page: 201710/TOMUDEX_PM.pdf - p.9	unhealthy n = 861 Health Status: unhealthy Condition: Colorectal Cancer Sex: M+F Population Size: 861 Sources: https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf Page: 201710/TOMUDEX_PM.pdf - p.9
Constipation	grade 3-4, 2%	3 mg/m2 1 times / 3 weeks multiple, intravenous Studied dose Dose: 3 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 3 mg/m2, 1 times / 3 weeks Sources: https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf Page: 201710/TOMUDEX_PM.pdf - p.9	unhealthy n = 861 Health Status: unhealthy Condition: Colorectal Cancer Sex: M+F Population Size: 861 Sources: https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf Page: 201710/TOMUDEX_PM.pdf - p.9
Oral soft tissue conditions	grade 3-4, 2.1%	3 mg/m2 1 times / 3 weeks multiple, intravenous Studied dose Dose: 3 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 3 mg/m2, 1 times / 3 weeks Sources: https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf Page: 201710/TOMUDEX_PM.pdf - p.9	unhealthy n = 861 Health Status: unhealthy Condition: Colorectal Cancer Sex: M+F Population Size: 861 Sources: https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf Page: 201710/TOMUDEX_PM.pdf - p.9
Blood bilirubin decreased	grade 3-4, 2.2%	3 mg/m2 1 times / 3 weeks multiple, intravenous Studied dose Dose: 3 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 3 mg/m2, 1 times / 3 weeks Sources: https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf Page: 201710/TOMUDEX_PM.pdf - p.9	unhealthy n = 861 Health Status: unhealthy Condition: Colorectal Cancer Sex: M+F Population Size: 861 Sources: https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf Page: 201710/TOMUDEX_PM.pdf - p.9
Thrombocytopenia	grade 3-4, 3.5%	3 mg/m2 1 times / 3 weeks multiple, intravenous Studied dose Dose: 3 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 3 mg/m2, 1 times / 3 weeks Sources: https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf Page: 201710/TOMUDEX_PM.pdf - p.9	unhealthy n = 861 Health Status: unhealthy Condition: Colorectal Cancer Sex: M+F Population Size: 861 Sources: https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf Page: 201710/TOMUDEX_PM.pdf - p.9
Infection	grade 3-4, 5%	3 mg/m2 1 times / 3 weeks multiple, intravenous Studied dose Dose: 3 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 3 mg/m2, 1 times / 3 weeks Sources: https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf Page: 201710/TOMUDEX_PM.pdf - p.9	unhealthy n = 861 Health Status: unhealthy Condition: Colorectal Cancer Sex: M+F Population Size: 861 Sources: https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf Page: 201710/TOMUDEX_PM.pdf - p.9
Hemoglobin decreased	grade 3-4, 6.5%	3 mg/m2 1 times / 3 weeks multiple, intravenous Studied dose Dose: 3 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 3 mg/m2, 1 times / 3 weeks Sources: https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf Page: 201710/TOMUDEX_PM.pdf - p.9	unhealthy n = 861 Health Status: unhealthy Condition: Colorectal Cancer Sex: M+F Population Size: 861 Sources: https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf Page: 201710/TOMUDEX_PM.pdf - p.9
Pain	grade 3-4, 7.3%	3 mg/m2 1 times / 3 weeks multiple, intravenous Studied dose Dose: 3 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 3 mg/m2, 1 times / 3 weeks Sources: https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf Page: 201710/TOMUDEX_PM.pdf - p.9	unhealthy n = 861 Health Status: unhealthy Condition: Colorectal Cancer Sex: M+F Population Size: 861 Sources: https://www.pfizer.ca/sites/default/files/201710/TOMUDEX_PM.pdf Page: 201710/TOMUDEX_PM.pdf - p.9

Details

SMILES

InChI

DescriptionSources: https://www.drugbank.ca/drugs/DB00293Curator's Comment: Description was created based on several sources, including https://www.medicines.org.uk/emc/medicine/2307 https://www.ncbi.nlm.nih.gov/pubmed/21148615

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Launch Date

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

PubMed

Patents

Sample Use Guides

Description
Sources: https://www.drugbank.ca/drugs/DB00293
Curator's Comment: Description was created based on several sources, including https://www.medicines.org.uk/emc/medicine/2307 https://www.ncbi.nlm.nih.gov/pubmed/21148615

C_max

T_1/2

F_unbound

Drug as perpetrator