Biomaterial Database

Phase I study of CI-958 in children and adolescents with recurrent solid tumors. 2001

C A Arndt, and M D Krailo, and W Liu-Mares, and P M Anderson, and G H Reaman

Department of Pediatrics, Division of Pediatric Hematology/Oncology, Mayo Clinic, Rochester, Minnesota, USA.

BACKGROUND CI-958 is a synthetic intercalating agent of a new chemical class, the benzopyranoindazoles, with promising preclinical activity. Its mechanism of action is thought to be stabilization of the cleavable complex of DNA with topoisomerase II, as well as DNA helicase blockade. It is thought to have less cardiotoxicity than the anthracyclines. Early Phase I studies in adults showed the drug to be well tolerated, making it an attractive agent to pursue in Phase I clinical trials in children. METHODS Children and adolescents with recurrent solid tumors received CI-958 at an initial dose of 450 mg/m(2) over 2 hours. Dose escalation was performed in a standard fashion in cohorts of three patients until dose limiting toxicity and the maximum tolerated dose were determined. RESULTS Twenty-one patients were entered on the study. The maximum tolerated dose was found to be 650 mg/m(2). Dose limiting toxicities were Grade 4 neutropenia and Grade 4 hypotension at the dose level of 700 mg/m(2). CONCLUSIONS The maximum tolerated dose of CI-958 in children and adolescents is 650 mg/m(2). No antitumor activity has been observed.

UI	MeSH Term	Description	Entries
D007022	Hypotension	Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.	Blood Pressure, Low,Hypotension, Vascular,Low Blood Pressure,Vascular Hypotension
D007191	Indazoles	A group of heterocyclic aromatic organic compounds consisting of the fusion of BENZENE and PYRAZOLES.	Indazole
D007262	Infusions, Intravenous	The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it.	Drip Infusions,Intravenous Drip,Intravenous Infusions,Drip Infusion,Drip, Intravenous,Infusion, Drip,Infusion, Intravenous,Infusions, Drip,Intravenous Infusion
D008297	Male		Males
D009369	Neoplasms	New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.	Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D009503	Neutropenia	A decrease in the number of NEUTROPHILS found in the blood.	Neutropenias
D002648	Child	A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL.	Children
D002675	Child, Preschool	A child between the ages of 2 and 5.	Children, Preschool,Preschool Child,Preschool Children
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260	Female		Females