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Hyaluronidase significantly enhances the efficacy of regional vinblastine chemotherapy of malignant melanoma

  • Original Paper
  • Experimental Oncology
  • Published:
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Abstract

The regional chemotherapy of the human malignant melanomas (SK-MEL-2, -3, -5, -24) implanted in NMRInu/nu mice with a combination of the hyaluronic-acid-cleaving enzyme hyaluronidase (HYase) and vinblastine is a very effective therapeutic procedure. In three out of four melanoma models (SK-MEL-2,-3, -5) the weekly peritumoral administration of high-dose HYase (100 000 IU/kg) 4 h prior to the injection of 0.3 mg/kg vinblastine in the vicinity of the tumor (seven weekly therapeutic cycles) caused marked antitumor effects, while HYase and vinblastine were inactive when given alone. The pretreatment with HYase, which is well tolerated by the test animals, prevented local inflammation reactions commonly seen after subcutaneous vinblastine administration. Tumor growth and metastatic behavior of the melanomas used were neither increased nor reduced by HYase after peritumoral administration without subsequent vinblastine injection. The curative activity of the regional chemotherapy with HYase/vinblastine could be demonstrated on the SK-Mel-3 melanoma. After an observation time of 18 weeks tumor cells could no longer be detected in the subcutaneous region of the former lesion. Only macrophages, which had abundantly incorporated melanin, gave evidence of previously growing tumors. In contrast to the controls, no metastases could be observed in the axillary lymph nodes of the test animals.

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Abbreviations

HA :

hyaluronic acid

T/C 100 X:

[median tumor area of therapy group (mm2)]/[median tumor area of control group (mm2)]

n :

number of animals per group

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Authors and Affiliations

  1. Institut für Pharmazie, Universität Regensburg, Universitätsstr. 31, D-93053, Regensburg, Germany

    Thilo Spruß, Günther Bernhardt & Helmut Schönenberger

  2. Sandoz-Gesellschaft m. b. H., Brunnerstr. 59, A-1235, Wien, Austria

    Wilfried Schiess

Authors
  1. Thilo Spruß
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  2. Günther Bernhardt
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  3. Helmut Schönenberger
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  4. Wilfried Schiess
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Spruß, T., Bernhardt, G., Schönenberger, H. et al. Hyaluronidase significantly enhances the efficacy of regional vinblastine chemotherapy of malignant melanoma. J Cancer Res Clin Oncol 121, 193–202 (1995). https://doi.org/10.1007/BF01366962

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  • DOI: https://doi.org/10.1007/BF01366962

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