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Comparison of Intravenous versus Intracarotid Therapy with 1,3-Bis(2-chloroethyi)-1-nitrosourea in a Rat Brain Tumor Model

Publication ,  Journal Article
Bullard, DE; Bigner, SH; Bigner, DD
Published in: Cancer Research
November 1, 1985

Currently numerous clinical trials are in progress utilizing intracarotid (i.c.) 1,3-bis(2-chloroethyl)-1 -nitrosourea (BCNU) for the treatment of malignant gliomas based upon the proposed focal nature of these tumors and the assumption that the i.e. route delivers higher levels of drug to the tumor. To date, however, increased efficacy in an animal model has not been clearly demonstrated for the i.e. delivery of BCNU. We have evaluated the dose-response curve for the i.v. and i.e. administration of BCNU in a commonly utilized experimental brain tumor model, the 9L rat gliosarcoma. An initial toxicity trial utilizing the i.p. 10% lethal dose (LD10) of BCNU by the i.v. and i.e. routes failed to demonstrate any significance in toxicity between the two routes. Tumor-bearing animals were then treated on Day 15-16 after tumor inoculations with 1,10, 25, 50,75, and 100% of the LD10 dose by either the i.v. or the i.e. route. Both i.v. and i.e. BCNU gave maximum survival increases at 75-100% LDi0doses, and there was no therapeutic advantage seen from i.e. delivery. However, at 50% of the LDi0 dose (6.65 mg/kg), triplicate experiments demonstrated that the i.e. but not the i.v. dose maintained maximum efficacy equivalent to 100% of the LD10 given either i.v. or i.e. When the dose was reduced to 25% of the LD10 dose (3.33 mg/kg), two of three experiments showed efficacy of the i.e. delivery of this lower drug dosage to be equivalent to 100% of the LD10 given i.v. or i.e. The i.v. dosage resulted in a significant reduction in survival in all three trials. At 10% of the LD10 dose (1.30 mg/kg), neither the i.v. nor the i.e. administration retained equivalent efficacy to 100% of the LD10. However, in one of two trials, the i.e. groups had statistically better survival than controls, while in neither experiment was any advantage over controls seen in the i.v. treated groups. At 1% of the LD10 dose, neither the i.v. nor the i.e. route demonstrated any therapeutic efficacy. From our data, the advantage of the i.e. delivery of BCNU in the intracranial 9L rat gliosarcoma appears to be in the fact that significantly lower dosages than those given i.v. may be utilized to achieve equivalent survival with potentially less systemic toxicity. © 1985, American Association for Cancer Research. All rights reserved.

Duke Scholars

Published In

Cancer Research

EISSN

1538-7445

ISSN

0008-5472

Publication Date

November 1, 1985

Volume

45

Start / End Page

5240 / 5245

Related Subject Headings

  • Oncology & Carcinogenesis
  • 1112 Oncology and Carcinogenesis
 

Citation

APA
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ICMJE
MLA
NLM
Bullard, D. E., Bigner, S. H., & Bigner, D. D. (1985). Comparison of Intravenous versus Intracarotid Therapy with 1,3-Bis(2-chloroethyi)-1-nitrosourea in a Rat Brain Tumor Model. Cancer Research, 45, 5240–5245.
Bullard, D. E., S. H. Bigner, and D. D. Bigner. “Comparison of Intravenous versus Intracarotid Therapy with 1,3-Bis(2-chloroethyi)-1-nitrosourea in a Rat Brain Tumor Model.” Cancer Research 45 (November 1, 1985): 5240–45.
Bullard, D. E., et al. “Comparison of Intravenous versus Intracarotid Therapy with 1,3-Bis(2-chloroethyi)-1-nitrosourea in a Rat Brain Tumor Model.” Cancer Research, vol. 45, Nov. 1985, pp. 5240–45.

Published In

Cancer Research

EISSN

1538-7445

ISSN

0008-5472

Publication Date

November 1, 1985

Volume

45

Start / End Page

5240 / 5245

Related Subject Headings

  • Oncology & Carcinogenesis
  • 1112 Oncology and Carcinogenesis