Effects of a controlled-release cisplatin delivery system used after resection of mammary carcinoma in mice

Nicole Ehrhart From the College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523 (N Ehrhart, Dernell, EJ Ehrhart, Hutchison, Straw, Withrow); the National Academy of Sciences, Washington, DC 20418 (Douple); and THM OSMED Inc, 325 S Lake Ave, Suite 608, Duluth, MN 55802 (Brekke).

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William S. Dernell From the College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523 (N Ehrhart, Dernell, EJ Ehrhart, Hutchison, Straw, Withrow); the National Academy of Sciences, Washington, DC 20418 (Douple); and THM OSMED Inc, 325 S Lake Ave, Suite 608, Duluth, MN 55802 (Brekke).

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E.J. Ehrhart From the College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523 (N Ehrhart, Dernell, EJ Ehrhart, Hutchison, Straw, Withrow); the National Academy of Sciences, Washington, DC 20418 (Douple); and THM OSMED Inc, 325 S Lake Ave, Suite 608, Duluth, MN 55802 (Brekke).

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Jennifer M. Hutchison From the College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523 (N Ehrhart, Dernell, EJ Ehrhart, Hutchison, Straw, Withrow); the National Academy of Sciences, Washington, DC 20418 (Douple); and THM OSMED Inc, 325 S Lake Ave, Suite 608, Duluth, MN 55802 (Brekke).

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Evan B. Douple From the College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523 (N Ehrhart, Dernell, EJ Ehrhart, Hutchison, Straw, Withrow); the National Academy of Sciences, Washington, DC 20418 (Douple); and THM OSMED Inc, 325 S Lake Ave, Suite 608, Duluth, MN 55802 (Brekke).

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John H. Brekke From the College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523 (N Ehrhart, Dernell, EJ Ehrhart, Hutchison, Straw, Withrow); the National Academy of Sciences, Washington, DC 20418 (Douple); and THM OSMED Inc, 325 S Lake Ave, Suite 608, Duluth, MN 55802 (Brekke).

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Rodney C. Straw From the College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523 (N Ehrhart, Dernell, EJ Ehrhart, Hutchison, Straw, Withrow); the National Academy of Sciences, Washington, DC 20418 (Douple); and THM OSMED Inc, 325 S Lake Ave, Suite 608, Duluth, MN 55802 (Brekke).

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Stephen J. Withrow From the College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523 (N Ehrhart, Dernell, EJ Ehrhart, Hutchison, Straw, Withrow); the National Academy of Sciences, Washington, DC 20418 (Douple); and THM OSMED Inc, 325 S Lake Ave, Suite 608, Duluth, MN 55802 (Brekke).

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Abstract

Objective

To evaluate efficacy of a controlled-release cisplatin delivery system, used after marginal resection of mammary carcinoma (ie, resection of grossly evident tumor) in mice, to prevent tumor regrowth and metastasis.

Animals

42 female C3H-HeJ mice.

Procedure

Mice were inoculated with mammary carcinoma cells. Between 2 and 6 days later, tumors were marginally resected and mice were assigned to 1 of 3 groups: no treatment (control; n = 14), cisplatin administered intraperitoneally (IP cisplatin; 14), and cisplatin delivered by use of an open-cell polylactic acid system placed within the tumor bed (slow-release cisplatin; 14). Tumor regrowth was measured daily. Mice were euthanatized 14 days after surgery, and complete necropsies were performed.

Results

Tumor regrowth was not detected in the slow-release cisplatin group; however, tumor regrowth was detected in 7 of 14 mice in the IP cisplatin group and 14 of 14 mice in the control group. Median (± SD) number of days to tumor regrowth was 13.5 ± 0.64 and 7.79 ± 0.87 in the IP cisplatin and control groups, respectively. Mice in the IP cisplatin group had significantly delayed tumor regrowth, compared with control mice. Metastases to lungs were detected in 8 of 14 control mice but were not detected in mice in either cisplatin treatment group.

Conclusions and Clinical Relevance

The open-cell polylactic acid with cisplatin delivery system was successful in delaying local tumor regrowth and metastasis in mice with marginally resected mammary carcinoma. Use of a controlled-release cisplatin delivery system may be an effective adjunct treatment following excision of mammary carcinoma in humans and other animals. (Am J Vet Res 1999;60:1347–1351)

Abstract

Objective

To evaluate efficacy of a controlled-release cisplatin delivery system, used after marginal resection of mammary carcinoma (ie, resection of grossly evident tumor) in mice, to prevent tumor regrowth and metastasis.

Animals

42 female C3H-HeJ mice.

Procedure

Mice were inoculated with mammary carcinoma cells. Between 2 and 6 days later, tumors were marginally resected and mice were assigned to 1 of 3 groups: no treatment (control; n = 14), cisplatin administered intraperitoneally (IP cisplatin; 14), and cisplatin delivered by use of an open-cell polylactic acid system placed within the tumor bed (slow-release cisplatin; 14). Tumor regrowth was measured daily. Mice were euthanatized 14 days after surgery, and complete necropsies were performed.

Results

Tumor regrowth was not detected in the slow-release cisplatin group; however, tumor regrowth was detected in 7 of 14 mice in the IP cisplatin group and 14 of 14 mice in the control group. Median (± SD) number of days to tumor regrowth was 13.5 ± 0.64 and 7.79 ± 0.87 in the IP cisplatin and control groups, respectively. Mice in the IP cisplatin group had significantly delayed tumor regrowth, compared with control mice. Metastases to lungs were detected in 8 of 14 control mice but were not detected in mice in either cisplatin treatment group.

Conclusions and Clinical Relevance

The open-cell polylactic acid with cisplatin delivery system was successful in delaying local tumor regrowth and metastasis in mice with marginally resected mammary carcinoma. Use of a controlled-release cisplatin delivery system may be an effective adjunct treatment following excision of mammary carcinoma in humans and other animals. (Am J Vet Res 1999;60:1347–1351)

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