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Comparison of intravenous versus intracarotid therapy with 1,3-bis(2-chloroethyl)-1-nitrosourea in a rat brain tumor model.

Publication ,  Journal Article
Bullard, DE; Bigner, SH; Bigner, DD
Published in: Cancer Res
November 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.c. 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.c. delivery of BCNU. We have evaluated the dose-response curve for the i.v. and i.c. 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.c. 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.c. route. Both i.v. and i.c. BCNU gave maximum survival increases at 75-100% LD10 doses, and there was no therapeutic advantage seen from i.c. delivery. However, at 50% of the LD10 dose (6.65 mg/kg), triplicate experiments demonstrated that the i.c. but not the i.v. dose maintained maximum efficacy equivalent to 100% of the LD10 given either i.v. or i.c. When the dose was reduced to 25% of the LD10 dose (3.33 mg/kg), two of three experiments showed efficacy of the i.c. delivery of this lower drug dosage to be equivalent to 100% of the LD10 given i.v. or i.c. 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.c. administration retained equivalent efficacy to 100% of the LD10. However, in one of two trials, the i.c. 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.c. route demonstrated any therapeutic efficacy. From our data, the advantage of the i.c. 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.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

November 1985

Volume

45

Issue

11 Pt 1

Start / End Page

5240 / 5245

Location

United States

Related Subject Headings

  • Rats
  • Oncology & Carcinogenesis
  • Male
  • Injections, Intravenous
  • Injections, Intra-Arterial
  • Disease Models, Animal
  • Carotid Arteries
  • Carmustine
  • Brain Neoplasms
  • Animals
 

Citation

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Bullard, D. E., Bigner, S. H., & Bigner, D. D. (1985). Comparison of intravenous versus intracarotid therapy with 1,3-bis(2-chloroethyl)-1-nitrosourea in a rat brain tumor model. Cancer Res, 45(11 Pt 1), 5240–5245.
Bullard, D. E., S. H. Bigner, and D. D. Bigner. “Comparison of intravenous versus intracarotid therapy with 1,3-bis(2-chloroethyl)-1-nitrosourea in a rat brain tumor model.Cancer Res 45, no. 11 Pt 1 (November 1985): 5240–45.
Bullard, D. E., et al. “Comparison of intravenous versus intracarotid therapy with 1,3-bis(2-chloroethyl)-1-nitrosourea in a rat brain tumor model.Cancer Res, vol. 45, no. 11 Pt 1, Nov. 1985, pp. 5240–45.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

November 1985

Volume

45

Issue

11 Pt 1

Start / End Page

5240 / 5245

Location

United States

Related Subject Headings

  • Rats
  • Oncology & Carcinogenesis
  • Male
  • Injections, Intravenous
  • Injections, Intra-Arterial
  • Disease Models, Animal
  • Carotid Arteries
  • Carmustine
  • Brain Neoplasms
  • Animals