HYALURONIDASE SIGNIFICANTLY ENHANCES THE EFFICACY OF REGIONAL VINBLASTINE CHEMOTHERAPY OF MALIGNANT-MELANOMA

The regional chemotherapy of the human malignant melanomas (SK-MEL-2, -3, -5, -24) implanted in NMRI nu/nu mice with a combination of the hy aluronic-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 hi gh-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 cyc les) 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 gr owth and metastatic behavior of the melanomas used were neither increa sed nor reduced by HYase after peritumoral administration without subs equent vinblastine injection. The curative activity of the regional ch emotherapy with HYase/vinblastine could be demonstrated on the SK-Mel- 3 melanoma. After an observation time of 18 weeks, tumor cells could n o longer be detected in the subcutaneous region of the former lesion. Only macrophages, which had abundantly incorporated melanin, gave evid ence of previously growing tumors. In contrast to the controls, no met astases could be observed in the axillary lymph nodes of the test anim als.