Long-term outcome associated with intratumoral chemotherapy with cisplatin for cutaneous tumors in equidae: 573 cases (1995–2004)

Alain P. Théon Departments of Surgery and Radiology, School of Veterinary Medicine, University of California, Davis, CA 95616.

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W. David Wilson Departments of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA 95616.

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K. Gary Magdesian Departments of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA 95616.

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Nicola Pusterla Departments of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA 95616.

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Jack R. Snyder Departments of Surgery and Radiology, School of Veterinary Medicine, University of California, Davis, CA 95616.

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Larry D. Galuppo Departments of Surgery and Radiology, School of Veterinary Medicine, University of California, Davis, CA 95616.

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Abstract

Objective—To determine outcome associated with cutaneous tumors treated via intratumoral chemotherapy with cisplatin and identify risk factors affecting local tumor control and complications in equidae.

Design—Retrospective case series.

Animals—573 equidae with 630 cutaneous tumors.

Procedures—Medical records of horses, mules, donkeys, and ponies with cutaneous tumors treated via intratumoral chemotherapy with cisplatin were analyzed.

Results—549 horses, 13 mules, 8 donkeys, and 3 ponies with 630 histologically confirmed cutaneous tumors were included. Tumors included sarcoids (n = 409), squamous cell carci nomas (151), soft tissue sarcomas (28), cutaneous lymphomas (26), and melanomas (16). Overall cure rate, defined as local control at 4 years, was 93.3%. For all tumor stages combined, cure rates after 1 course of treatment were 96.3% for sarcoids, 96% for lym-phomas, 88% for squamous cell carcinomas, 85% for soft tissue sarcomas, and 81% for melanomas. Treatment protocol, tumor stage, and prior treatment were significant prog nostic factors for tumor control. Treatment efficacy was lower for large tumors, those with gross postoperative residual disease, and those that had been treated previously with other modalities. Treatment was well tolerated. Local reactions were more likely to occur and to be more severe after the third and fourth treatment sessions.

Conclusions and Clinical Relevance—Results confirmed the value of intratumoral chemotherapy with cisplatin for treatment of cutaneous tumors in equidae.The results cannot be extrapolated to other formulations of cisplatin or other protocols that might be used.

Abstract

Objective—To determine outcome associated with cutaneous tumors treated via intratumoral chemotherapy with cisplatin and identify risk factors affecting local tumor control and complications in equidae.

Design—Retrospective case series.

Animals—573 equidae with 630 cutaneous tumors.

Procedures—Medical records of horses, mules, donkeys, and ponies with cutaneous tumors treated via intratumoral chemotherapy with cisplatin were analyzed.

Results—549 horses, 13 mules, 8 donkeys, and 3 ponies with 630 histologically confirmed cutaneous tumors were included. Tumors included sarcoids (n = 409), squamous cell carci nomas (151), soft tissue sarcomas (28), cutaneous lymphomas (26), and melanomas (16). Overall cure rate, defined as local control at 4 years, was 93.3%. For all tumor stages combined, cure rates after 1 course of treatment were 96.3% for sarcoids, 96% for lym-phomas, 88% for squamous cell carcinomas, 85% for soft tissue sarcomas, and 81% for melanomas. Treatment protocol, tumor stage, and prior treatment were significant prog nostic factors for tumor control. Treatment efficacy was lower for large tumors, those with gross postoperative residual disease, and those that had been treated previously with other modalities. Treatment was well tolerated. Local reactions were more likely to occur and to be more severe after the third and fourth treatment sessions.

Conclusions and Clinical Relevance—Results confirmed the value of intratumoral chemotherapy with cisplatin for treatment of cutaneous tumors in equidae.The results cannot be extrapolated to other formulations of cisplatin or other protocols that might be used.

  • 1

    Lippert B. Cisplatin: chemistry and biochemistry of a leading anticancer drug. New York: Wiley-VCH, 1999.

  • 2

    Goldberg EP, Hadba AR, Almond BA, et al. Intratumoral cancer chemotherapy and immunotherapy: opportunities for non-systemic preoperative drug delivery. J Pharm Pharmacol 2002;54:159180.

    • Search Google Scholar
    • Export Citation
  • 3

    Deurloo MJ, Bohlken S, Kop W, et al. Intratumoural administration of cisplatin in slow-release devices. I. Tumour response and toxicity. Cancer Chemother Pharmacol 1990;27:135140.

    • Search Google Scholar
    • Export Citation
  • 4

    Bergerat JP, Barlogie B, Drewinko B. Effects of cis-dichlorodiammineplatinum(II) on human colon carcinoma cells in vitro. Cancer Res 1979;39:13341338.

    • Search Google Scholar
    • Export Citation
  • 5

    Fuertesa MA, Castillab J, Alonsoa C, et al. Cisplatin biochemical mechanism of action: from cytotoxicity to induction of cell death through interconnections between apoptotic and necrotic pathways. Curr Med Chem 2003;10:257266.

    • Search Google Scholar
    • Export Citation
  • 6

    Begg AC, Bartelink H, Stewart FA, et al. Improvement of differential toxicity between tumor and normal tissues using intratumoral injection with or without a slow-drug-release matrix system. NCI Monogr 1988;133136.

    • Search Google Scholar
    • Export Citation
  • 7

    Tamzali Y, Teissie J, Rols MP. Cutaneous tumor treatment by electrochemotherapy: preliminary clinical results in horse sarcoids. Révue de Médècine Vétérinaire 2001;152:605609.

    • Search Google Scholar
    • Export Citation
  • 8

    Theon AP, Pascoe JR, Carlson GP, et al. Intratumoral chemotherapy with cisplatin in oily emulsion in horses. J Am Vet Med Assoc 1993;202:261267.

    • Search Google Scholar
    • Export Citation
  • 9

    Deurloo MJ, Kop W, van Tellingen O, et al. Intratumoural administration of cisplatin in slow-release devices: II. Pharma-cokinetics and intratumoural distribution. Cancer Chemother Pharmacol 1991;27:347353.

    • Search Google Scholar
    • Export Citation
  • 10

    Chen FA, Kuriakose MA, Zhou MX, et al. Biodegradable polymer-mediated intratumoral delivery of cisplatin for treatment of human head and neck squamous cell carcinoma in a chimeric mouse model. Head Neck 2003;25:554560.

    • Search Google Scholar
    • Export Citation
  • 11

    Krag DN, Theon AP, Schneider PD, et al. Intralesional cis-diamminedichloroplatinum and purified collagen treatment of human metastatic malignancies: a feasibility study. J Surg Oncol 1990;43:8387.

    • Search Google Scholar
    • Export Citation
  • 12

    Duvillard C, Romanet P, Cosmidis A, et al. Phase 2 study of intratumoral cisplatin and epinephrine treatment for locally recurrent head and neck tumors. Ann Otol Rhinol Laryngol 2004;113:229233.

    • Search Google Scholar
    • Export Citation
  • 13

    Kempf W, Dummer R, Schmid MH, et al. Intralesional cisplatin for the treatment of cutaneous B-cell lymphoma. Arch Dermatol 1998;134:13431345.

    • Search Google Scholar
    • Export Citation
  • 14

    Oratz R, Hauschild A, Sebastian G, et al. Intratumoral cisplatin/adrenaline injectable gel for the treatment of patients with cutaneous and soft tissue metastases of malignant melanoma. Melanoma Res 2003;13:5966.

    • Search Google Scholar
    • Export Citation
  • 15

    Kitchell BE, Brown DM, Luck EE, et al. Intralesional implant for treatment of primary oral malignant melanoma in dogs. J Am Vet Med Assoc 1994;204:229236.

    • Search Google Scholar
    • Export Citation
  • 16

    Orenberg EK, Luck EE, Brown DM, et al. Implant delivery system: intralesional delivery of chemotherapeutic agents for treatment of spontaneous skin tumors in veterinary patients. Clin Dermatol 1991;9:561568.

    • Search Google Scholar
    • Export Citation
  • 17

    Théon AP, Madewell BR, Ryu J, et al. Concurrent irradiation and intratumoral chemotherapy with cisplatin: a pilot study in dogs with spontaneous tumors. Int J Radiat Oncol Biol Phys 1994;29:10271034.

    • Search Google Scholar
    • Export Citation
  • 18

    Théon AP, Pascoe JR, Galuppo LD, et al. Comparison of peri-operative versus postoperative intratumoral administration of cisplatin for treatment of cutaneous sarcoids and squamous cell carcinomas in horses. J Am Vet Med Assoc 1999;215:16551660.

    • Search Google Scholar
    • Export Citation
  • 19

    Spoormakers TJ, Klein WR, Jacobs JJ, et al. Comparison of the efficacy of local treatment of equine sarcoids with IL-2 or cisplatin/IL-2. Cancer Immunol Immunother 2003;52:179184.

    • Search Google Scholar
    • Export Citation
  • 20

    Knottenbelt DC, Kelly DF. The diagnosis and treatment of periorbital sarcoid in the horse: 445 cases from 1974 to 1999. Vet Ophthalmol 2000;3:169191.

    • Search Google Scholar
    • Export Citation
  • 21

    Strubbe DT. Periocular neurofibrosarcoma in a horse. Vet Ophthalmol 2001;4:237241.

  • 22

    Théon AP, Pascoe JR, Madigan JE, et al. Comparison of intratumoral administration of cisplatin versus bleomycin for treatment of periocular squamous cell carcinomas in horses. Am J Vet Res 1997;58:431436.

    • Search Google Scholar
    • Export Citation
  • 23

    Owen LN. TNM classification of tumours in domestic animals. Geneva: World Health Organization, 1980;1213.

  • 24

    Théon AP. Cisplatin treatment for cutaneous tumors. In:Robinson NE, ed.Current therapy in equine medicine. 4th ed.Philadephia: WB Saunders Co, 1997;372377.

    • Search Google Scholar
    • Export Citation
  • 25

    Théon AP. Intralesional and topical chemotherapy and immunotherapy. Vet Clin North Am Equine Pract 1998;14:659671, viii.

  • 26

    Kaplan EL, Meier P. Non-parametric estimation from incomplete observations. J Am Stat Assoc 1958;54:457481.

  • 27

    Cox DR. Regression models and life tables'series B (methodological). J R Stat Soc 1972;34:187220.

  • 28

    Théon AP, Pascoe JR, Meagher DM. Perioperative intratumoral administration of cisplatin for treatment of cutaneous tumors in equidae. J Am Vet Med Assoc 1994;205:11701176.

    • Search Google Scholar
    • Export Citation
  • 29

    Harrell FE, Lee KL, Pollock BG. Regression models in clinical studies: determining the relationship between predictors and response. J Natl Cancer Inst 1988;80:198202.

    • Search Google Scholar
    • Export Citation
  • 30

    Kitchell BK, Orenberg EK, Brown DM, et al. Intralesional sustained-release chemotherapy with therapeutic implants for treatment of canine sun-induced squamous cell carcinoma. Eur J Cancer 1995;31A:20932098.

    • Search Google Scholar
    • Export Citation
  • 31

    Johnson PJ. Dermatologic tumors (excluding sarcoids). Vet Clin North Am Equine Pract 1998;14:625658, viii.

  • 32

    Goodrich L, Gerber H, Marti E, et al.Equine sarcoids. Vet Clin North Am Equine Pract 1998;14:607623, vii.

  • 33

    Théon AP. Radiation therapy in the horse. Vet Clin North Am Equine Pract 1998;14:673688, viii.

  • 34

    Rebhun WC. Tumors of the eye and ocular adnexal tissues. Vet Clin North Am Equine Pract 1998;14:579606, vii.

  • 35

    Boure L, Krawiecki JM, Thoulon F. Trial treatment of sarcoids in horses with intratumoral injections of bleomycin. Point Vétérinaire 1991;23:199204.

    • Search Google Scholar
    • Export Citation
  • 36

    Yu NY, Conley FK, Luck EE, et al. Response of murine tumors to matrix-associated cisplatin intratumoral implants. NCI Monogr 1988;137140.

    • Search Google Scholar
    • Export Citation
  • 37

    Yu NY, Orenberg EK, Luck EE, et al. Antitumor effect of intratumoral administration of fluorouracil/epinephrine injectable gel in C3H mice. Cancer Chemother Pharmacol 1995;36:2734.

    • Search Google Scholar
    • Export Citation
  • 38

    Kontochristopoulos G, Stefanaki C, Panagiotopoulos A, et al. Intralesional 5-fluorouracil in the treatment of keloids: an open clinical and histopathologic study. J Am Acad Dermatol 2005;52:474479.

    • Search Google Scholar
    • Export Citation
  • 39

    Iscimen A, Aydemir EH, Goksugur N, et al. Intralesional 5-fluorouracil, lidocaine and epinephrine mixture for the treatment of verrucae: a prospective placebo-controlled, single-blind randomized study. J Eur Acad Dermatol Venereol 2004;18:455458.

    • Search Google Scholar
    • Export Citation
  • 40

    Miller BH, Shavin JS, Cognetta A, et al. Nonsurgical treatment of basal cell carcinomas with intralesional 5-fluorouracil/epinephrine injectable gel. J Am Acad Dermatol 1997;36:7277.

    • Search Google Scholar
    • Export Citation
  • 41

    Castro DJ, Sridhar KS, Garewal HS, et al. Intratumoral cisplatin/epinephrine gel in advanced head and neck cancer: a multicenter, randomized, double-blind, phase III study in North America. Head Neck 2003;25:717731.

    • Search Google Scholar
    • Export Citation
  • 42

    Stewart AA, Rush B, Davis E. The efficacy of intratumoural 5-fluorouracil for the treatment of equine sarcoids. Aust Vet J 2006;84:101106.

    • Search Google Scholar
    • Export Citation
  • 43

    Tsujimoto H, Hagiwara A, Sakakura C, et al. Cisplatin microcrystals suspended in oil—toxicity in mice. Anticancer Drugs 1993;4:377380.

    • Search Google Scholar
    • Export Citation
  • 44

    Mir LM, Glass LF, Sersa G, et al. Effective treatment of cutaneous and subcutaneous malignant tumours by electrochemotherapy. Br J Cancer 1998;77:23362342.

    • Search Google Scholar
    • Export Citation
  • 45

    Wenzel M, Schneider M, Bier J. [Toxicity and cytostatic effect of PtCl2(NH3)2 after i. v. and i. t. injection (author's transl)]. Z Naturforsch [C] 1980;35:848850.

    • Search Google Scholar
    • Export Citation
  • 46

    Howe-Grant ME, Lippard SJ. Aqueous platinum(II) chemistry; binding to biological molecules. In:Sigel H, ed.Metal ions in biological systems. New York: Marcel Dekker Inc, 1980;63125.

    • Search Google Scholar
    • Export Citation
  • 47

    Landrito JE, Yoshiga K, Sakurai K, et al. Effects of intralesional injection of cisplatin dissolved in urografin and lipiodol on Ehrlich ascites tumor and normal tissues of CD-1 mice. Cancer Chemother Pharmacol 1994;34:323330.

    • Search Google Scholar
    • Export Citation
  • 48

    Spoormakers TJ, Klein WR, van Weeren PR. Treatment of equine sarcoids with cisplatin in arachid oil: a useful alternative? [in Dutch]. Tijdschr Diergeneeskd 2002;127:350354.

    • Search Google Scholar
    • Export Citation
  • 49

    Honnas CM, Liskey CC, Meagher DM, et al. Malignant melanoma in the foot of a horse. J Am Vet Med Assoc 1990;197:756758.

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