what are the reactions to chemo with dogs

• Periodical Listing
• Tin Vet J
• 5.fifty(6); 2009 Jun
• PMC2684058

Tin Vet J. 2009 Jun; l(half-dozen): 665–668.

Chemotherapy: Managing side effects and safe handling

Chemotherapy is a common treatment modality in many veterinary cancer patients in improver to surgery and radiation therapy. Cytotoxic drugs tin can atomic number 82 to complete remissions for some disseminated cancers (lymphoma, for case), exist constructive in decreasing tumor size, and may prolong life in many other types of metastatic cancers, such as osteosarcoma. The choice of specific therapies depends on tumor type (what it is), histologic grade of the tumor (how aggressive it is), stage of disease (where it is), and the patient'south (just mainly the pet owner's) tolerance for the side effects of the various treatments. Nigh of the chemotherapy protocols designed for veterinary patients have a < v% incidence of severe, life-threatening complications (1). Virtually veterinarian chemotherapy patients enjoy a expert quality of life while on therapy. This article will discuss some of the side furnishings associated with chemotherapy in veterinarian patients and how to finer treat them. In addition, an overview of chemotherapy safe for both patient and veterinary staff will be discussed.

Veterinarians engaging in the practice of oncology require a thorough cognition of the effects and toxicities of anticancer drugs. Since these agents possess the lowest therapeutic indices of whatsoever class of drugs, they produce frequent and predictable multi-arrangement toxicities. Apprehension of possible complications and shut attention to subtle clinical signs are essential to assure early on introduction of prophylactic or therapeutic supportive intendance. Toxicities are virtually often acute, but chronic or delayed effects practise occur. An alphabetize of suspicion for these problems is essential for their diagnosis. The Veterinary Cooperative Oncology Group (VCOG) has published a certificate outlining the mutual terminology criteria and providing a grading scale for agin events post-obit chemotherapy (2).

Merely put, chemotherapy kills apace dividing cells. Unfortunately chemotherapy drugs do non differentiate between killing tumor cells and normal cells. Thus, the general side effects of chemotherapy include bone marrow suppression, gastrointestinal problems (nausea, vomiting, diarrhea), and baldness (1). However, in addition to the general side furnishings seen, specific side effects can issue from certain drugs, for case, doxorubicin (cardiotoxicity) and cisplatin (fatal pulmonary edema in cats, renal toxicity in dogs).

The nigh mutual toxicity associated with chemotherapy is bone marrow suppression. Bone marrow cells separate apace because at that place is unremarkably a high growth fraction in this tissue. Since action of most anticancer drugs is greatest in tissues with a high growth fraction, the bone marrow is a prime target. The clinical issue of myelosuppression is varying degrees of peripheral blood cytopenias. The rate of disappearance of individual blood jail cell lines correlates with the life bridge of that line. For example: RBC — 120 d (dogs), seventy d (cats); platelets — 5 to ten d; granulocytes — 4 to 8 h. Granulocytopenia (specifically neutropenia) usually occurs first and is most often followed past thrombocytopenia. Anemia is rare and usually only balmy to moderate.

Neutropenia is usually the most serious and dose limiting cytopenia associated with chemotherapeutic drug administration. The nadir (time of the lowest neutrophil count) varies with private drugs. Nadirs in pocket-size animals occur between 5 to 10 d — standard exercise is to run a complete blood (jail cell) count (CBC) at 7 d post-chemotherapy administration in lodge to find the nadir, though the nadir can exist missed. It is important to note that some drugs accept a delayed or second nadir at about 21 d (carboplatin, for case) (i). Neutrophil counts usually rebound from the nadir within ane to 3 d. Immature granulocytes are an indicator for return of granulocytic action. Animals with < thousand neutrophils/μL are at an increased risk for sepsis and require close monitoring. Neutrophil counts < 500/μL (categorized every bit a class iv neutropenia) usually are associated with fever and sepsis (ane). In add-on to lower neutrophil counts, chemotherapy can result in gastrointestinal epithelial desquamation, and the combination of these factors tin lead to increased opportunity for enteric leaner to enter the circulation causing septicemia, with fewer phagocytic neutrophils to finer articulate the infection which tin can exist life-threatening.

Treating the neutropenic patient

Oncologists have diverse cutoff values that they adhere to when deciding whether or not chemotherapy will be administered. This writer's cutoff value is one.five × 10^ix cells/L (1500 cells/μL) for neutrophils and 75 × 10^nine/L (75 000 cells/μL) for platelets. Animals with neutropenia (< 1500 cells/μL) that are afebrile and asymptomatic should have chemotherapy delayed for a few days to 1 wk based on the severity. A broad spectrum antibiotic should be administered for v d if the neutrophil count is less than ane.0 × 10⁹ cells/50 (1000 cells/μL). Chemotherapy may be restarted one time the neutrophil count and platelet count have increased to the advisable minimal cutoff level. Many oncologists will reduce the dose past 20% if in that location is a treatment delay; however, this author only reduces the dose when a class four neutropenia has occurred. It is reported that when a dose is reduced past xx%, the efficacy of the therapy is reduced past 50% (3).

If the patient is neutropenic and febrile with or without clinical signs (such equally vomiting, diarrhea, trembling, aridity, weakness, lethargy) chemotherapy should be discontinued. In some cases, a fever may not be present just the patient has clinical signs. The patient should be hospitalized on intravenous fluids and antibiotics, such as ampicillin and enrofloxacin in combination, to cover both gram-positive and gram-negative bacteria (4). Other symptomatic support should be provided such as parenteral nutrition and anti-emetics such as Maropitant (Cerenia), Ondansetron (Zofran) and/or Metoclopramide (Reglan). If the patient is non responding to antibody therapy, claret cultures should be considered. Fever usually responds inside 12 to 24 h.

Neutropenia cannot ever be prevented; all the same, tactics such every bit monitoring CBCs weekly or at the time of the expected nadir, checking for occult infections such as in the urinary tract or pare prior to therapy, and reducing chemotherapy drug doses in patients that have previously shown extreme sensitivity to these agents may exist helpful in reducing its occurrence. Controversy still surrounds the practise of administering prophylactic antibiotics to patients receiving chemotherapy. In one report from the human literature, a review was performed to assess the evidence for the effectiveness of oral safe antibiotics to subtract bacteremia and infection-related mortality in oncology patients during neutropenic episodes (5). The study concluded that these antibiotics decreased gram-negative bacteremia and therefore infection-related bloodshed. No evidence of bacterial resistance to these antibiotics was reported. In the veterinary literature, the use of oral prophylactic trimethoprim/sulfonamide (TMS) was constitute to exist beneficial for reducing multiple toxicities during chemotherapy with doxorubicin (half dozen). Careful monitoring of the patient is recommended to address the possibility of potential resistance.

Gastrointestinal toxicity

Although nearly animals tolerate chemotherapy treatments very well, some animals volition accept gastrointestinal side furnishings such as vomiting, diarrhea, and/or decreased appetite. There may be various reasons for these side furnishings. There can be a direct stimulatory effect past the drug on the CNS vomiting center or chemoreceptor trigger zone (CRTZ). This vomiting will occur during or presently afterwards drug administration and can final for 1 to 2 d (4). The usual culprit for this firsthand vomiting is Cisplatin — the reason why an anti-emetic is typically given prior to its assistants (ane). Chemotherapy can too have an indirect effect secondary to drug induced gastrointestinal inflammation and damage. This damage usually occurs iii to 5 d mail treatment. Gastrointestinal side effects may range from mild, such every bit a day of inappetence and soft stool, to severe with protracted vomiting and bloody diarrhea leading to dehydration. Treatment is usually symptomatic. If the signs are mild, patients can be managed at home. Zero per os (NPO) for a day followed by a bland diet is usually sufficient. Animals that are more severely affected may require hospitalization with IV fluids and anti-emetics.

Chemosafety

Many veterinarians in general do are administering chemotherapy either on their own or with the guidance of a veterinary oncologist. Chemotherapy can exist used in full general practise provided the post-obit: that biosafety rules are strictly adhered to by all personnel straight and indirectly involved with the patient and drugs, patient prophylactic is a priority, and that the practitioner is knowledgeable well-nigh all aspects of the drug to exist used prior to its administration.

Safety for y'all and your staff

Safe handling of chemotherapy drugs cannot be overemphasized! Safety protocols tin exist posted everywhere in a dispensary but it is everyone's responsibility to understand and follow these protocols, otherwise, they are just written words on a piece of paper. To ensure your own safety and that of your staff, the best way to avoid unnecessary exposure to potential toxins is by using proper handling techniques. Chemotherapy exposure occurs three ways: droplets, topical, and oral. To reduce or preclude exposure the following protocols are recommended:

1. Prepare chemotherapy drugs in a sterile smoke hood (Figure 1). At the WCVM and other specialty clinics, this is a reasonable pick but nigh veterinarian practices do not accept hoods. Therefore, a quiet room on a clean surface away from ventilation ducts is recommended. An canonical chemotherapy mask, gown, and gloves must be worn while preparing chemotherapy agents. There are now commercially available closed systems that reduce the run a risk of aerosolization such as PhaSeal. At the WCVM, we have but started using this organization to reduce the risk of exposure fifty-fifty further. In addition, all chemotherapy is placed in a sealed plastic bag after it is prepared to reduce contagion of surfaces (Figure 2).

   

   Chemotherapy agent drawn up in a sterile fumehood. Notation that both gown and gloves are worn.

   

   Once the chemotherapy amanuensis is prepared, the syringe is placed in a labeled sealed plastic bag. This process prevents contagion of surfaces and provides a disposal for all used chemotherapy waste.

2. Approved chemotherapy administration gloves are preferable to latex examination gloves that are not impermeable to chemotherapy agents. If chemotherapy administration gloves are non available, double gloving with latex test gloves is acceptable. A nonabsorbent chemotherapy administration gown or, at minimum, a clean buttoned upward lab coat should exist worn during administration. A mask and protective eye-wear should as well be worn. This protective clothing should be worn past both the "giver" and the "holder" (Figure 3).

   

   Sit-in of chemotherapy administration — note gown, gloves, and mask.

3. No food or beverage should be in the chemotherapy administration room. A refrigerator should be assigned for chemotherapy drugs only and food should never exist stored in the aforementioned identify.

4. Once you are finished administering the drug, all chemotherapy waste (syringe, IV catheter, bandages, etc) should be returned to the sealed plastic bag and disposed of with other Biohazardous Waste according to government regulations in your area and not thrown in a sharps container or garbage.

5. Because chemotherapy drugs are excreted in feces and urine, we advise clients to wear gloves when cleaning upward afterwards their pets for up to 48 h after drug administration and wash the area with diluted bleach. Presently there are no written guidelines that exist for the disposal of pet waste.

6. It is recommended that significant or nursing staff refrain from existence involved with treatment chemotherapy drugs and patient waste. If there are inquiries as to other individuals who may be at increased risk (immunocompromised), consider discussing the situation with a md.

7. A pre-existing protocol should be in place (for instance, spill-kit, emergency procedures) should a spill occur.

Condom for your patient

Regardless of the type of drug you are using, information technology is essential to know how to administer it (oral, subcutaneous, intramuscular, or intravenous) and in one case information technology is given what full general and specific side effects may occur. For example, L-asparaginase is a safe and well tolerated drug when administered subcutaneously or intra-muscularly. If given intravenously, L-asparaginase will effect in a (potentially fatal) anaphylactic reaction (1). Another of import case is cyclophosphamide, an alkylating agent that is effective confronting a broad range of tumors. A major side effect that may occur fifty-fifty after a single dose is sterile hemorrhagic cystitis. This side upshot can greatly alter quality of life for a patient, thus, by taking simple precautionary measures such as administering cyclophosphamide with either prednisone or furosemide (1 mg/kg one time), we can greatly reduce this problem (ane).

Since most chemotherapeutics are administered intravenously, a well-placed catheter is essential. If the vein has been recently used, or if yous have already damaged the vein in an attempt to place a catheter, get to a new leg. "Fishing" for the vein cannot be washed as you are potentially putting microtears in the vessel with each "stick." This author always uses the jugular vein for taking blood samples and saves peripheral veins for chemotherapy assistants. Having an indwelling catheter should prevent adventitious extravasation of tissue irritants such equally vincristine, vinblastine, or doxorubicin. Be sure to flush the catheter with 0.9% sodium chloride before and after administration of the chemotherapy drug.

If strict adherence to Iv catheter rules occurs, extravasation can almost be eliminated; however, accidents can still occur. If extravasation occurs with a balmy/moderate vesicant such as vincristine or vinblastine, you should aspirate the drug out of the site if possible. Marker the surface area with an enduring marker so the afflicted area can exist observed. Inflammation and edema can be reduced past applying warm compresses to the site for 10 to 15 min every 6 h for 24 to 48 h. Even though the resulting tissue impairment can sometimes be meaning, it rarely results in the loss of the limb.

However, if a severe vesicant like doxorubicin is extravasated, the resulting damage can be then severe that it may warrant amputation or even euthanasia of the patient (Figure iv) (one). If extravasation occurs, try to aspirate every bit much drug as possible. Do not flush the area with saline in an attempt to dilute the drug; this will only spread the drug farther into the tissue. Place another Four catheter in a different leg and administer dexrazoxane (Zinecard) at 10 × the dose of doxorubicin (if the dose of doxorubicin was 20 mg, then administer 200 mg of Zinecard). The initial dose should exist given within 3 h of extravasation and then again within 24 and 48 h. While no clinical trial has been reported for using this protocol, anecdotal reports in client-owned patients have shown that this arroyo works and has profoundly lessened the severity of tissue damage. If dexrazoxane is not available, early surgical debridement can exist washed.

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A mixed breed dog receiving chemotherapy for Phase 3 lymphoma adult a severe reaction after extravasation of doxorubicin that was noted at the fourth dimension of the infusion. Images of the left thoracic limb demonstrate the appearance of the lesions at (a) six days, (b) 10 days, and (c) 17 days post-infusion. An amputation of the afflicted limb was performed at 21 days postinfusion. The dog had a permanent draining tract after amputation and was euthanized before long after.

Acknowledgments

The author thank you Dr. Emma Felton, Pathway Animal Hospital, Roseburg, Oregon, USA for providing the photographs in Figure 4. Photographs 1 to 3 were taken by Myrna MacDonald, WCVM.

Footnotes

Use of this commodity is limited to a single copy for personal study. Anyone interested in obtaining reprints should contact the CVMA office ( gro.vmca-amvc@nothguorbh) for additional copies or permission to utilize this fabric elsewhere.

References

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2. Group VCO. Veterinarian Co-operative Oncology Grouping-Common Terminology Criteria for Adverse Events (VCOG-CTCAE) post-obit chemotherapy or biological antineoplastic therapy in dogs and cats v1.0. Vet Compar Oncol. 2004;2:194–213. [PubMed] [Google Scholar]

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4. Kisseberth WC, MacEwen EG. Complications of Cancer and Its Treatment. In: Withrow SJ, MacEwen EG, editors. Small Animal Clinical Oncology. third ed. Philadelphia: Saunders; 2001. pp. 198–232. [Google Scholar]

5. Van de Wetering MD, de Witte MA, Kremer LCM, Offringa M, Scholten RJPM, Caron HN. Efficacy of oral rubber antibiotics in neutropenic afebrile oncology patients: A systematic review of randomized controlled trials. Eur J of Cancer. 2005;41:1372–1382. [PubMed] [Google Scholar]

vi. Chretin JD, Rassnick KM, Shaw NA, et al. Condom trimethoprim-sulfadiazine during chemotherapy in dogs with lymphoma and ostoesarcoma: A double-blind, placebo-controlled study. J Vet Intern Med. 2007;21:141–148. [PubMed] [Google Scholar]

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Articles from The Canadian Veterinarian Periodical are provided here courtesy of Canadian Veterinary Medical Association

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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2684058/

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