In vitro evaluation of in vivo brain tumor chemotherapy with 1,3-bis(2-chloroethyl)-1-nitrosourea

Journal Article · Sun Jun 01 04:00:00 EDT 1975 · Cancer Res.; (United States)

OSTI ID:7195104

Rosenblum, M L; Wheeler, K T; Wilson, C B; Barker, M; Knebel, K D

An in vitro colony formation assay was used to determine the efficacy of in vivo therapy with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) on a rat brain tumor. The fraction of clonogenic cells surviving in vivo therapy was determined by a comparison between the in vitro colony-forming capacity of cells derived from previously treated and untreated tumors. With this intracerebral solid tumor a direct correlation was found between the surviving fraction of cells and animal survival, implying that the in vitro assay system is a reliable test of therapeutic effect. The BCNU dose-response curve was exponential up to a dose of 0.75 times the LD/sub 10/ dose with little additional cell kill noted at higher drug levels. This plateau does not appear to represent a resistant subpopulation of cells, since retreatment of tumors derived from cells surviving an LD/sub 10/ dose were as sensitive to BCNU as those with no prior drug exposure. Instead, it may represent, at least in part, failure of the drug to reach and/or enter cells in all parts of solid tumors. On the average BCNU doses of 0.75 times the LD/sub 10/ dose or greater resulted in slightly more than a 3-log cell kill and doubled the life-span for our tumor-bearing animals. The finding that an increase in animal life-span requires at least a 1-log tumor cell kill indicates that survival studies with intracranial tumor models may be insensitive to single courses or many chemotherapeutic agents with modest but significant antitumor activity. (auth)

• Research Organization: Univ. of California, San Francisco
• OSTI ID: 7195104
• Journal Information: Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 35; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

550900* -- Pathology
59 BASIC BIOLOGICAL SCIENCES
AMIDES
ANIMALS
BODY
BRAIN
CARBONIC ACID DERIVATIVES
CENTRAL NERVOUS SYSTEM
CHEMOTHERAPY
DISEASES
DOSE-RESPONSE RELATIONSHIPS
IN VITRO
IN VIVO
MAMMALS
NEOPLASMS
NERVOUS SYSTEM
NITROSO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
RATS
RODENTS
SURVIVAL TIME
THERAPY
UREA
VERTEBRATES