Combined Therapy with Carboplatin and Meloxicam for Oral Squamous Cell Carcinoma in a Dog

구강 편평 세포암 이환견에서 Carboplatin과 Meloxicam의 병용투여 증례

  • Jang, Hwan-Soo (College of Veterinary Medicine, Kyungpook National University) ;
  • Kim, Jun-Il (Plus Animal Hospital) ;
  • Kim, Jae-Hoon (College of Veterinary Medicine, Jeju National University) ;
  • Jang, Kwang-Ho (College of Veterinary Medicine, Kyungpook National University)
  • Accepted : 2010.12.14
  • Published : 2011.06.30

Abstract

A 16-year-old, spayed female, Maltese dog weighing 4.3 kg was presented with a 2-week history of yellowish nose-and oral-discharge, anorexia and lethargy. In physical examination, indefinite ulcerative mass about $3{\times}3$ cm in size in the left sublingual region, severe gingivoperiodontitis, halitosis, moderate dental calculus, fever and swelling of mandible soft tissue were noted. In radiographic view, periodontitis and bone lysis findings on the left rostral part of maxilla and mandible were observed. In complete blood count and blood chemistry test, thrombocytosis, increased levels of serum $NH_3$, AST and ALP were obtained. Urinalysis revealed hematuria and proteinuria. In histological examination, squamous cell carcinoma was diagnosed. No surgery was performed, but combined treatment with carboplatin and piroxicam was initiated. Five days after initiation of medication, because of insistent vomiting, piroxicam was substituted to meloxicam. Although the therapeutic efficacy of meloxicam could not be known; administration of meloxicam might be less potential to gastrointestinal side-effects than piroxicam. The dog totally received 3 times of carboplatin infusion. Five days after third infusion of carboplatin, the dog was hospitalized with severe lethargy, vomiting and bloody diarrhea. In examination, severe renal failure signs were noted, and the dog was euthanized.

체중이 4.3 kg인 중성화된 16세의 암컷 말티즈견이 약 2주 동안 누런색의 비강과 구강 분비물, 식욕부진과 기면 증상으로 내원하였다. 신체검사에서 구강내 왼쪽 혀 밑 부위에 약 $3{\times}3$ cm 크기의 궤양성 종괴, 심한 치은치주염, 구취, 중등도의 치석, 발열과 아래턱의 연조직 부종을 관찰하였다. 방사선 사진상에서 위턱과 아래턱의 앞 부위에서 골융해 소견을 볼 수 있었다. 총혈액검사와 혈액화학검사에서 혈소판수치, $NH_3$, AST와 ALP의 증가를 관찰할 수 있었으며, 요검사에서 혈뇨와 단백뇨가 나타났다. 조직검사결과 구강 편평 세포암으로 진단되었다. 축주의 거부로 외과적 처치는 실시하지 않았으며, 약물요법으로 carboplatin 주사와 piroxicam 구강내 투여를 병용하였다. 처음 약물투여 후 5일에 지속적인 구토 증상이 나타났으며, 이에 piroxicam을 meloxicam으로 대체하였으며 구토증상은 소실되었다. Meloxicam의 종양에 대한 치료효과에 대한 보고는 흔하지 않지만, 위장관계에 대한 부작용 발생은 piroxicam에 비해 낮음을 알 수 있었다. 이환견은 총 3회의 carboplatin 주사를 실시하였으나, 세 번째 주사 투여 후 5일에 심한 기면증상, 구토와 혈변 증상으로 내원하였고, 검사결과 심한 신기능부전 소견을 보였으며, 축주의 요구에 의해 안락사하였다.

Keywords

References

  1. Boria PA, Murry DJ, Bennett PF, Glickman NW, Snyder PW, Merkel BL, Schlittler DL, Mutsaers AJ, Thomas RM, Knapp DW. Evaluation of cisplatin combined with piroxicam for the treatment of oral malignant melanoma and oral squamous cell carcinoma in dogs. J Am Vet Med Assoc 2004; 224: 388-394. https://doi.org/10.2460/javma.2004.224.388
  2. Brooks MB, Matus RE, Leifer CE, Alfieri AA, Patnaik AK. Chemotherapy versus chemotherapy plus radiotherapy in the treatment of tonsillar squamous cell carcinoma in the dog. J Vet Intern Med 1988; 2: 206-211. https://doi.org/10.1111/j.1939-1676.1988.tb00318.x
  3. Cohen D, Brodey RS, Chen SM. Epidemiologic Aspects of Oral and Pharyngeal Neoplasms of the Dog. Am J Vet Res 1964; 25: 1776-1779.
  4. de Vos JP, Burm AG, Focker AP, Boschloo H, Karsijns M, van der Waal I. Piroxicam and carboplatin as a combination treatment of canine oral non-tonsillar squamous cell carcinoma: a pilot study and a literature review of a canine model of human head and neck squamous cell carcinoma. Vet Comp Oncol 2005; 3: 16-24. https://doi.org/10.1111/j.1476-5810.2005.00065.x
  5. Grier CK, Mayer MN. Radiation therapy of canine nontonsillar squamous cell carcinoma. Can Vet J 2007; 48: 1189-1191.
  6. Henkels KM, Turchi JJ. Carboplatin-induced apoptosis proceeds by caspase-3-dependent and independent pathways in cisplatin-rresistant and sensitive human ovarian cancer. Cancer Res 1999; 59: 3077-3083.
  7. Kosovsky JK, Matthiesen DT, Marretta SM, Patnaik AK. Results of partial mandibulectomy for the treatment of oral tumors in 142 dogs. Vet Surg 1991; 20: 397-401. https://doi.org/10.1111/j.1532-950X.1991.tb00346.x
  8. Liptak JM, Withrow SJ. Cancers of the Gastrointestinal tract. In: Small Animal Clinical Oncology, 4th ed. Philadelphia: Saunders Elsevier. 2007: 455-475.
  9. MacMillan R, Withrow SJ, Gillette EL. Surgery and regional irradiation for treatment of canine tonsillar squamous cell carcinoma: retrospective review of eight cases. J Am Anim Hosp Associ 1982; 18: 311-314.
  10. Makitie AA, Chau M, Lim S, Viani MA, Gilbert R, Lim MS, Jordan RC. Selective inhibition of cyclooxygenase 2 induces p27kip1 and skp2 in oral squamous cell carcinoma. J Otolaryngology 2003; 32: 226-229. https://doi.org/10.2310/7070.2003.41701
  11. Mohammed SI, Bennett PF, Craig BA, Glickman NW, Mutsaers AJ, Snyder PW, Widmer WR, De Nicola DB, Knapp DW. Effects of the cyclooxgenase inhibitor, piroxicam, on tumor response, apoptosis, and angiogenesis in a canine model of human invasive urinary bladder cancer. Cancer Res 2002; 62: 356-358.
  12. Mohammed SI, Coffman K, Glickman NW, Hayek MG, Waters DJ, Schlittler D, DeNicola DB, Knapp DW. Prostaglandin E2 concentrations in naturally occurring canine cancer. Prostaglandins Leukot Essent Fatty Acids 2001; 64: 1-4. https://doi.org/10.1054/plef.2000.0231
  13. Mohammed SI, Craig BA, Mutsaers AJ, Glickman NW, Snyder PW, de Gortari AE, Schlittler DL, Coffman KT, Bonney PL, Knapp DW. Effects of cyclooxygenase inhibitor, piroxicam, in combination with chemotherapy on tumor response, apoptosis, and angiogenesis in a canine model of human invasive urinary bladder cancer. Mole Cancer Ther 2003; 2: 183-188. https://doi.org/10.4161/cbt.2.2.350
  14. Schmidt BR, Glickman NW, DeNicola DB, de Gortari AE, Knapp DW. Evaluation of piroxicam for the treatment of oral squamous cell carcinoma in dogs. J Am Vet Med Assoc 2001; 218: 1783-1786. https://doi.org/10.2460/javma.2001.218.1783
  15. Wallace J, Matthiesen DT, Patnaik AK. Hemimaxillectomy for the treatment of oral tumors in 69 dogs. Vet Surg 1992; 21: 337-341. https://doi.org/10.1111/j.1532-950X.1992.tb01707.x