Intratumoral Cisplatin in Combination with Betulinic Acid in a Radiation and Chemoresistant Squamous Cell Carcinoma - Case Report
World Small Animal Veterinary Association World Congress Proceedings, 2004
M. Willmann1, K.Grösslinger1, B. Wolfesberger1, M. Pagitz1, S. Shibly1, J. Hassan2, R. Paschke5, B. Jansen4, E. Selzer3
Department for Small Animals and Horses1, Department for Diagnostics2; University of Veterinary Medicine, Vienna, Austria; Department for Radiotherapy and Radiobiology3, University of Medicine Vienna, Wien, Austria; University of British Columbia, Vancouver, Canada4; Martin-Luther-Universität, Biozentrum, Halle / Saale, Germany5

Case history

We here present a case-study of a ten year old mixbreed dog with an unilateral left sided carcinoma of the ostium nasi extending into the nasal cavity. Tumor staging procedures included thoracic radiographs and CT-scan and provided no evidence for further spread of the disease. Chest radiographs were negative but CT imaging revealed an infiltrative growth into adjacent bony structures. No signs of lymph-node involvement were observed. We performed cytoreductive surgery because of tumor-induced airway obstruction. After surgery, irradiation was performed with single doses of 8 Gy up to a total dose of 36 Gy. Four months after surgery and postoperative radiotherapy, a local recurrence was observed. A treatment-attempt was made with retinoids and piroxicam but after one month we noted progressive growth of the tumor extending into the right nasal planum leading to recurrent bilateral epistaxis. Due to the lack of further treatment options, we decided to investigate a novel compound (betulinic acid) in combination with cisplatin. After obtaining the owners freely-given informed consent we initiated therapy. The dog was anesthetized during treatment procedures for about 20 minutes. The tumor and the surrounding tissue was infiltrated with a combination of both cytotoxic agents (1mg/cm<sup>3<sup> cisplatin and 0,5mg/m<sup>3<sup> betulinic acid) without any adverse local effects during the treatment period. As expected, no cisplatin-related systemic toxicities were observed. The complete treatment consisted of 6 sessions of intratumoral chemotherapy at 3-week intervals. After two courses, tumor was significantly reduced and finally had disappeared clinically after 3 months. Four months after the end of therapy there was no evidence of tumor.

Discussion

Despite curative and intensive therapy including surgery, chemotherapy and irradiation, progressive disease occurred in a patient with a squamous cell carcinoma of the nose. A novel combination utilizing betulinic acid in conjunction with cisplatin led to a complete remission in this patient. This is the first report to provide evidence for the potential of a combination therapy encompassing cisplatin and betulinic acid in an otherwise treatment-resistant carcinoma of the nose.

References

1.  Pisha,-E. et-al., (1995), Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis. Nat-Med. Oct; 1(10): 1046-51.

2.  Selzer,-E; et al., (2002), Betulinic acid-induced Mcl-1 expression in human melanoma--mode of action and functional significance. Mol-Med. Dec; 8(12): 877-84.

3.  Thurnher, D. et al., (2003), Betulinic acid: a new cytotoxic compound against malignant head and neck cancer cells. Head-Neck. Sep; 25(9): 732-40.

Speaker Information
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M. Willmann
Department for Small Animals and Horses
University of Veterinary Medicine
Vienna, Austria


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