Intralesional implant for treatment of primary oral malignant melanoma in dogs

Barbara E. Kitchell From Special Veterinary Services, Berkeley, CA 94704 (Kitchell); Matrix Pharmaceutical Inc, 1430 O'Brien Dr, Menlo Park, CA 94025 (Brown, Luck, Woods, Orenberg); and the Biomedical Statistics Department, Stanford University, Stanford, CA 94305-5410 (Bloch).

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Dennis M. Brown From Special Veterinary Services, Berkeley, CA 94704 (Kitchell); Matrix Pharmaceutical Inc, 1430 O'Brien Dr, Menlo Park, CA 94025 (Brown, Luck, Woods, Orenberg); and the Biomedical Statistics Department, Stanford University, Stanford, CA 94305-5410 (Bloch).

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Edward E. Luck From Special Veterinary Services, Berkeley, CA 94704 (Kitchell); Matrix Pharmaceutical Inc, 1430 O'Brien Dr, Menlo Park, CA 94025 (Brown, Luck, Woods, Orenberg); and the Biomedical Statistics Department, Stanford University, Stanford, CA 94305-5410 (Bloch).

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Laure L. Woods From Special Veterinary Services, Berkeley, CA 94704 (Kitchell); Matrix Pharmaceutical Inc, 1430 O'Brien Dr, Menlo Park, CA 94025 (Brown, Luck, Woods, Orenberg); and the Biomedical Statistics Department, Stanford University, Stanford, CA 94305-5410 (Bloch).

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Elaine K. Orenberg From Special Veterinary Services, Berkeley, CA 94704 (Kitchell); Matrix Pharmaceutical Inc, 1430 O'Brien Dr, Menlo Park, CA 94025 (Brown, Luck, Woods, Orenberg); and the Biomedical Statistics Department, Stanford University, Stanford, CA 94305-5410 (Bloch).

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Daniel A. Bloch From Special Veterinary Services, Berkeley, CA 94704 (Kitchell); Matrix Pharmaceutical Inc, 1430 O'Brien Dr, Menlo Park, CA 94025 (Brown, Luck, Woods, Orenberg); and the Biomedical Statistics Department, Stanford University, Stanford, CA 94305-5410 (Bloch).

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Summary

The feasibility, safety, and efficacy of a new method of local, sustained-release chemotherapy by use of intralesional cisplatin implants were evaluated in the treatment of oral malignant melanoma. The implant is an injectable viscous gel composed of a protein carrier matrix, a vasoactive modifier, and a chemotherapeutic drug. Twenty dogs with biopsy- proven melanomas were treated at 1- to 2-week intervals by injection with cisplatin implant. Tumors were treated until they resolved or were judged to be unresponsive. In 3 dogs with tumors unresponsive to cisplatin implants, methotrexate implants were used, and in 2 of these dogs, carmustine implants followed the methotrexate. Tumor responses were evaluated by sequential measurements.

Melanomas in 14 (70%) of 20 dogs had a > 50% decrease in volume, and in 11 (55%) of these dogs, had a complete response. Tumors with complete responses received a mean cisplatin dose of 11.7 ± 1.8 mg, delivered in a mean of 2.6 treatments. Two of the dogs with complete response also were treated with methotrexate and carmustine. Implants were well tolerated. Local necrosis, limited to the treatment site, developed in most tumors (17/20) and was associated with tumor response. Systemic toxicosis was minimal; renal insufficiency after cisplatin implants was not evident.

Median survival times of dogs with complete tumor response (51 weeks) was substantially greater than that of dogs without local tumor control (10.5 weeks). Recursive partitioning analysis of variables indicated that mandibular tumors of short duration were associated with a positive outcome. Multivariate linear regression analysis revealed the benefit of a greater number of cisplatin implants in a consistent weekly treatment course. The success of the intralesional chemotherapy indicated that implants are a technically feasible modality for local control of oral melanomas in dogs and provide possible alternative treatment to radiation therapy or surgery.

Summary

The feasibility, safety, and efficacy of a new method of local, sustained-release chemotherapy by use of intralesional cisplatin implants were evaluated in the treatment of oral malignant melanoma. The implant is an injectable viscous gel composed of a protein carrier matrix, a vasoactive modifier, and a chemotherapeutic drug. Twenty dogs with biopsy- proven melanomas were treated at 1- to 2-week intervals by injection with cisplatin implant. Tumors were treated until they resolved or were judged to be unresponsive. In 3 dogs with tumors unresponsive to cisplatin implants, methotrexate implants were used, and in 2 of these dogs, carmustine implants followed the methotrexate. Tumor responses were evaluated by sequential measurements.

Melanomas in 14 (70%) of 20 dogs had a > 50% decrease in volume, and in 11 (55%) of these dogs, had a complete response. Tumors with complete responses received a mean cisplatin dose of 11.7 ± 1.8 mg, delivered in a mean of 2.6 treatments. Two of the dogs with complete response also were treated with methotrexate and carmustine. Implants were well tolerated. Local necrosis, limited to the treatment site, developed in most tumors (17/20) and was associated with tumor response. Systemic toxicosis was minimal; renal insufficiency after cisplatin implants was not evident.

Median survival times of dogs with complete tumor response (51 weeks) was substantially greater than that of dogs without local tumor control (10.5 weeks). Recursive partitioning analysis of variables indicated that mandibular tumors of short duration were associated with a positive outcome. Multivariate linear regression analysis revealed the benefit of a greater number of cisplatin implants in a consistent weekly treatment course. The success of the intralesional chemotherapy indicated that implants are a technically feasible modality for local control of oral melanomas in dogs and provide possible alternative treatment to radiation therapy or surgery.

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