Abstract
There is epidemiologic evidence showing a strong association between the administration of inactivated feline vaccines (or other injectables) and subsequent development of soft tissue sarcomas at vaccine sites in cats 1,2,3 . The prevalence of soft tissue sarcomas after vaccination varies between 1/1000 and 1/10 000. If these prevalence rates are to be applied to the 1991 United States cat population, a total of 22 000 vaccine-associated tumours occurred in 1991.
Recommendations for preventing or decreasing the prevalence of injection-site sarcomas in cats are controversial, and include a change in vaccination site location, decreased use of polyvalent vaccines, use of non-adjuvanted vaccines, avoiding the use of aluminum-based adjuvants, and not overvaccinating, among others.
The most important recommendation for prevention of injection-site tumours would appear to be not to overvaccinate. Kas, et al. (1993) 2 has clearly shown that the risk of injection-site tumours increases with the number of vaccines administered. It is also clear from recently published articles by Scott et al. (1997) 4 that the duration of immunity of many of the commercially available vaccines for cats is longer than 1 year, and an every 3 year programme should be instituted for many vaccines for infectious agents of cats. With respect to rabies vaccination, annual vaccination for rabies with a 3-year rabies product should be discouraged (malpractice?). The indiscriminate use of feline leukaemia virus vaccine should be stopped since epidemiologic data suggest it may be the number one cause of injection-site sarcomas in cats. Very few now recommend FeLV vaccination for strictly indoor cats.
Vaccine site location recommendations have also changed. The National Sarcoma Task Force studying vaccine site tumours recommends that no vaccine be given in the interscapular space, that rabies be administered in the distal right rear leg, that leukaemia be administered in the distal left rear leg, and that all other vaccines be administered in the right shoulder. It appears from our research and reports by others that both intramuscular and subcutaneous administration result in local inflammation and tumour induction. Subcutaneous sites are recommended for all vaccines since they will result in earlier detection of these growths. The reasoning behind recommending these vaccine administration sites is not based so much on prevention but rather on earlier diagnosis potentially leading to a higher cure rate when treated surgically.
The issue of monovalent and polyvalent vaccines is still controversial. Kass (1993) 2 found a significant positive trend in risk with an increasing number of vaccines. However, Hendrick et al. 1 found no association between vaccination site and non-vaccination site tumours in the number of vaccinations given simultaneously. Although ambiguity exists, it seems prudent to now recommend that vaccines be administered at different sites and not to use polyvalent vaccines.
The use of vaccines containing aluminum-based adjuvants is controversial. The recommendation not to use multiple dose vials for aluminum adjuvanted vaccines appears less controversial, and aluminum adjuvanted products are the most consistent producer of vaccine site inflammation and, in our opinion, should be avoided if possible! However, non-aluminum-based adjuvants have also been linked to tumour production, and may be equally unsafe. In 1985, we traded a MLV rabies vaccine that produced problems in 1/500 000 for a killed adjuvanted rabies vaccine that produced tumours in 1/1000 cats. Boy we were smart!
It would appear that the problem of injection-site sarcomas will be with us for some time, and the question of what to do with post-vaccination lumps is a real one. We follow the following guidelines: some rabies and FeLV vaccines produce post-vaccinal lumps in 100% of the vaccinates but, fortunately, most go away in 2–3 months. Very few injection-site tumours occur sooner than 3 months following vaccination. Given these facts, we recommend that any vaccine site lumps present after 3 months of the time of vaccination be biopsied and, if malignant, surgically excised. An incisional biopsy will determine the magnitude of the surgery, ie, lumpectomy vs aggressive surgery. Attempts at simple excision of these tumours is seldom curative and ultimately leads to local recurrence with a more difficult second attempt. Even attempts at aggressive wide surgical excision are often incomplete and result in a 30%–70% failure rate. There appears to be an advantage to refer these cases to a qualified surgeon before the second surgery is contemplated, or better yet, for the first surgery! Rear leg amputation has a higher rate of cure than surgery in the interscapular space for injection-site sarcomas. Given the incomplete removal of these tumours even with aggressive surgery, radiation is often used either before or after surgery. One study's interim survival analysis indicates a doubling of survival times when radiation is included. Although the combination of surgery and radiation therapy has increased tumour control rates, a high number of cats still fail this combination.
Several chemotherapy agents, including carboplatin (Paraplatin), doxorubicin (Adriamycin), mitoxantrone (Novantrone), cyclophosphamide (Cytoxan), and vincristine (Oncovin), have been used in cats with injection-site tumours. Most chemotherapeutic protocols result in partial responses but some complete responses occur. Combinations of doxorubicin (1 mg/kg, IV, on day 1 of a 21 day cycle) and cyclophosphamide (200–300 mg/m2, PO, on day 10 of the cycle), mitoxantrone (4–6 mg/m2, IV, on day 1 of a 21 day cycle) and cyclophosphamide (200 300 mg/m2, PO, on day 10 of the cycle), or single-agent carboplatin (Paraplatin 250 mg/m2, IV, every 3 to 4 weeks) have resulted in some partial and complete remissions; however, sarcomas in cats are not very chemoresponsive. Although the vast majority of injection-site tumours are only locally invasive, approximately 10 to 25% metastasise to the lungs, eyes, or other sites.
The cost of these treatments can be high and run into many thousands of dollars. The ethics of the profession and how we manage this problem are being watched by many, including the media. How we act on this issue is likely to have a profound effect on how our profession is perceived by the public for some time in the future.
Given the need for vaccination against rabies to prevent a lethal disease in cats and humans, there would appear to be a need to compensate owners for expenses associated with the treatment of tumours that develop after the administration of mandated vaccines like rabies. Perhaps it is time that the veterinary profession consider a vaccine injury act similar to the 1986 Childhood Vaccine Injury Act in use for humans injured by mandated vaccines such as DPT and MMR. More legislative support is also needed and required in truth in labelling of veterinary vaccines that have been associated with vaccine site sarcoma development. Currently, a 3-year rabies vaccine may be relabelled as a 1-year rabies vaccine. Currently, annual revaccination for FeLV is recommended, without having any evidence of duration of immunity.