Evaluation of Ophthalmological Side Effects of Two Different Doses of Tamoxifen in Female Dogs
C.B. Campos; W.L.F. Tavares; M.S. Figueiredo; A.G. Souza; F.A.B. Viana; M.M. Melo; G.D. Cassali
Laboratório de Patologia Comparada, Departamento de Patologia Geral, ICB/UFMG, Belo Horizonte, MG, Brazil
Mammary tumors are the most frequent neoplasia in female dogs. Despite the importance and high frequency of mammary tumors in bitches, tumoral extirpations followed by ovariohysterectomy are the commonly utilized strategies for the animal's treatment. However, it is estimated that approximately 48% of bitches die or are euthanized after one year of surgical intervention. Therefore, it is evident that the adoption of low cost therapeutic alternatives is necessary in order to promote enlargement of the animal's survival time and improve quality of life. The aim of this study is to evaluate ophthalmological side effects of two different doses of Tamoxifen in female dogs, under human species criteria, to help evaluate viability and standardize the most adequate dose for the canine species (Baker 1994, Morris et al. 1993).
Materials and Methods
Healthy bitches with 20 kg medium weight, originated from the Zoonosis Control Center of Belo Horizonte/Brazil were evaluated. Initially, the animals were submitted to ophthalmological evaluations. After, the animals were randomly distributed in 4 treatment groups during 4 months: A) 5 intact bitches--0.5 mg/kg/day dose, B) 5 spayed bitches--0.5 mg/kg/day dose, C) 5 intact bitches--0.8 mg/kg/day dose, and D) 5 spayed bitches--0.8 mg/kg/day dose. The drug assessment occurred every 10 days through complete clinical examination and other analyses that will be described in future studies. Animals that presented ophthalmological alterations before Tamoxifen administrations were censured (animals: A4, B3 and C5). Therefore 17 animals were evaluated at the baseline, after 60 and 120 days of Tamoxifen administration. This experiment was approved by the animal experimentation ethics committee--CETEA, protocol number 40/2006.
Four animals were evaluated in group A. Ophthalmological alterations such as retinopathy were only observed after 120 days of treatment, in 50% of the animals. Four animals were evaluated in group B. The same ophthalmological alterations as black dots in the perimacular and fovea areas were observed in 25% of the animals after 60 days of Tamoxifen administration. The percentage remained unaltered until 120 days. No ophthalmological alterations were observed in the four animals evaluated from group C throughout the 120 day period. Five animals were evaluated in group D, 40% presented the ophthalmological alterations described above after 120 days of Tamoxifen administration.
Discussion & Conclusions
After 120 days of treatment, 29.4% of the 17 evaluated animals presented ophthalmological alterations similar to those observed in women, although only 6.3% of women are affected. (Lazzaroni et al. 1998, Noureddin et al. 1993, Tang et al. 1997) This difference might occur due to a greater sensibility of female dogs when compared to women. This drug acts more as an agonist then as an antagonist in the canine specie, suggesting that there are specific differences among species. (Pavlidis et al. 1992) No significant difference was observed among groups of reduced (A and B) and superior (C and D) dose. However, animals from the reduced dose group (A and B) presented injuries originating after 60 days of evaluation, suggesting an individual and systematic analysis, independently of dose and hormonal situation (spayed or intact animals). Tamoxifen has contributed to breast cancer treatment in women for over 30 years. In human medicine, ophthalmological alterations are reversible after treatment interruption and are compatible patient's quality of life because of the beneficial effects of Tamoxifen, e.g., survival increase in women suffering from breast cancer (Pavlidis et al. 1992). These alterations are expected to be reversible in the canine species after treatment interruption. Ophthalmological collateral effects of Tamoxifen observed in the bitches of this study did not compromise the animal's quality of life.
1. Baker RW. 1994. Comments to the editor on "Use of tamoxifen in the control of canine mammary neoplasia". Vet. Rec. 134(1):24.
2. Morris JS, Dobson JM, Bostock DE. 1993. Use of tamoxifen in the control of canine mammary neoplasia. Vet. Rec. 27:539-541.
3. Lazzaroni F, Scorolli L, Pizzoleo CF, Savini G, De Nigris A, Giosa F, Meduri RA. 1998. Tamoxifen retinopathy: does it really exist? Graefes Arch. Clin. Exp. Ophthalmol. 236(6):669-673.
4. Noureddin BN, Seoud M, Bashshur Z, Salem Z, Shamseddin A, Khalili A. 1993. Ocular toxicity in low-dose tamoxifen: a prospective study. Eye 13(Pt 6a):729-733.
5. Tang R, Shields J, Schiffman J, Li H, Locher D, Hampton J, Prager T, Pardo G. 1997. Retinal changes associated with Tamoxifen treatment for breast cancer. Eye 12(Pt 3a):295-297.
6. Pavlidis NA, Petris C, Briassoulis E, Klouvas G, Psilas C, Rempapis J, Petroutsos G. Clear evidence that long-term, low-dose tamoxifen treatment can induce ocular toxicity. A prospective study of 63 patients. Cancer 69(12):2961-2964.