Treating lymphoma in dogs and cats

Because single-agent lomustine has demonstrated therapeutic activity for the treatment of refractory canine lymphoma, intuitively, it would be expected that lomustine should possess efficacy when used against drug-naïve, high-grade, multicentric canine lymphoma. Given lomustine's oral formulation, relative low cost, therapeutic effectiveness against refractory lymphomas, and reported low incidence of hepatotoxicity, lomustine appears to be an excellent anticancer drug, but keep in mind that conventional, multiagent systemic chemotherapy is still considered the gold standard for treating canine lymphoma. Carefully consider using single-agent lomustine as a first-line treatment option, and make sure you understand and recognize the potential hazards of using lomustine.

FIGURE 6. A laparoscopic view of the gross morphologic appearance of the liver in a standard poodle with hepatotoxicity attributed to chronic lomustine therapy. Morphologic changes are not specific for lomustine-induced hepatotoxicity.

As already demonstrated in dogs treated for refractory lymphoma, the long-term administration of lomustine may result in cumulative thrombocytopenia. When lomustine is used in a rescue setting, lomustine-induced cumulative thrombocytopenia may be of marginal consequence because few effective treatment options remain for heavily treated, relapsing patients. However, in dogs with relapsing lymphoma treated with first-line lomustine, cumulative thrombocytopenia may limit the safe institution of additional myelosuppressive agents, including doxorubicin and cyclophosphamide. In addition to cumulative thrombocytopenia, lomustine's hepatotoxic potential should be carefully considered before its liberal use in cancer-bearing dogs (Figure 6). Although the reported rate of hepatotoxicity is quite low, a recent abstract suggests that the incidence of hepatotoxicity, defined as greater than fourfold elevations in serum alanine transaminase activities, is much higher in dogs treated with a combination of lomustine and oral prednisone. In this study, 23 of 45 dogs treated with lomustine and prednisone had moderately to severely elevated serum alanine transaminase activities.¹⁹ Additionally, most dogs (74%) developed pathologic serum alanine transaminase activity elevations with three or fewer lomustine treatments. These findings suggest that combining lomustine with prednisone may markedly increase the likelihood for acute liver injury, and veterinary practitioners should vigilantly monitor patients with serial serum chemistry profiles before each subsequent dose of lomustine, whether alone or in combination with prednisone. Lomustine should be considered a viable treatment option for dogs with lymphoma, especially in a rescue setting. However, the recommended use of lomustine as a first-line, single-agent should be reserved primarily for pet owners who actively choose to forgo conventional multiagent chemotherapy for their ailing pets. Currently, no published reports define the efficacy of first-line, single-agent lomustine for the treatment of canine lymphoma. Until that information becomes available, it remains difficult to enthusiastically recommend single-agent lomustine therapy rather than the use of a known effective monotherapy such as doxorubicin.

Adjuvant radiation Radiation therapy induces programmed cell death in both normal and malignant lymphocytes. Given the sensitivity of malignant lymphocytes to radiation-induced injury, the efficacy of external beam, megavoltage radiation therapy has been evaluated for the adjuvant treatment of high-grade, multicentric lymphoma in dogs. In one study, 52 dogs were treated with a short course of induction chemotherapy (11 weeks), immediately followed by staged, half-body irradiation.²⁰ Radiation therapy was administered to cranial and caudal body halves for a total dose of 8 Gy, given in two fractions of 4 Gy on consecutive days with cobalt-60 photons and a three-week interval between halves. The side effects associated with half-body irradiation were generally mild and included reversible myelosuppression and gastrointestinal upset. In addition to the safety of combined chemotherapy and adjuvant radiation, the investigated protocol was therapeutically effective, with treated patients achieving a first median remission time of 311 days.²⁰ The findings of this study emphasize that long-lasting remissions can be achieved in dogs with lymphoma by using short treatment protocols that combine chemotherapy and radiation.
Nodal irradiation for chemoresistant lymphoma
Malignant lymphocytes expressing multidrug-resistant phenotypes are afforded a survival advantage when exposed to cytotoxic agents. Attempting to treat resistant lymphocyte clones, even with novel chemotherapeutic agents, still may result in disease progression. Because of the limitations of chemical cytotoxic agents, in conjunction with the inherent radiosensitivity of malignant lymphocytes, the use of total lymphoid irradiation (TLI) for confirmed chemoresistant lymphoma has been investigated. In one study, 11 dogs with confirmed multidrug-resistant lymphoma were treated with total nodal irradiation. A dose of 2 Gy given in six fractions over two weeks was administered to all affected peripheral lymph nodes. By the fourth radiation fraction, all treated lymph nodes had returned to normal size, and dogs treated with nodal irradiation survived for a median of 143 days.²¹ The results of this pilot study demonstrate that dogs with chemoresistant lymphoma may still appreciably benefit from alternative treatment options such as nodal irradiation.
TREATING FELINE LYMPHOMA
Systemic chemotherapy

TABLE 3. Summary of Selected Feline Lymphoma Protocols

Unlike canine lymphoma in which several innovative treatment options have been investigated, the treatment of cats with high-grade lymphoma has not markedly changed during the past decade. Several systemic chemotherapeutic protocols have been evaluated for treating feline lymphoma (Table 3). In general, with the institution of multiagent systemic chemotherapy, most (about 60% to 70%) cats will achieve complete remission, with median survival times approximating six to nine months.¹ Although the treatment of cats with lymphoma has not changed greatly over the past several years, it has been suggested that cats diagnosed with lymphoma are afforded with better quality-of-life scores and survival times, as compared with a decade ago. In part, this suggestion is based on the dramatic decrease in the number of cats infected with FeLV, a reported negative prognostic factor in cats with lymphoma.²²

Because single-agent lomustine has demonstrated therapeutic activity for the treatment of refractory canine lymphoma, intuitively, it would be expected that lomustine should possess efficacy when used against drug-naïve, high-grade, multicentric canine lymphoma. Given lomustine's oral formulation, relative low cost, therapeutic effectiveness against refractory lymphomas, and reported low incidence of hepatotoxicity, lomustine appears to be an excellent anticancer drug, but keep in mind that conventional, multiagent systemic chemotherapy is still considered the gold standard for treating canine lymphoma. Carefully consider using single-agent lomustine as a first-line treatment option, and make sure you understand and recognize the potential hazards of using lomustine.

FIGURE 6. A laparoscopic view of the gross morphologic appearance of the liver in a standard poodle with hepatotoxicity attributed to chronic lomustine therapy. Morphologic changes are not specific for lomustine-induced hepatotoxicity.

As already demonstrated in dogs treated for refractory lymphoma, the long-term administration of lomustine may result in cumulative thrombocytopenia. When lomustine is used in a rescue setting, lomustine-induced cumulative thrombocytopenia may be of marginal consequence because few effective treatment options remain for heavily treated, relapsing patients. However, in dogs with relapsing lymphoma treated with first-line lomustine, cumulative thrombocytopenia may limit the safe institution of additional myelosuppressive agents, including doxorubicin and cyclophosphamide. In addition to cumulative thrombocytopenia, lomustine's hepatotoxic potential should be carefully considered before its liberal use in cancer-bearing dogs (Figure 6). Although the reported rate of hepatotoxicity is quite low, a recent abstract suggests that the incidence of hepatotoxicity, defined as greater than fourfold elevations in serum alanine transaminase activities, is much higher in dogs treated with a combination of lomustine and oral prednisone. In this study, 23 of 45 dogs treated with lomustine and prednisone had moderately to severely elevated serum alanine transaminase activities.¹⁹ Additionally, most dogs (74%) developed pathologic serum alanine transaminase activity elevations with three or fewer lomustine treatments. These findings suggest that combining lomustine with prednisone may markedly increase the likelihood for acute liver injury, and veterinary practitioners should vigilantly monitor patients with serial serum chemistry profiles before each subsequent dose of lomustine, whether alone or in combination with prednisone. Lomustine should be considered a viable treatment option for dogs with lymphoma, especially in a rescue setting. However, the recommended use of lomustine as a first-line, single-agent should be reserved primarily for pet owners who actively choose to forgo conventional multiagent chemotherapy for their ailing pets. Currently, no published reports define the efficacy of first-line, single-agent lomustine for the treatment of canine lymphoma. Until that information becomes available, it remains difficult to enthusiastically recommend single-agent lomustine therapy rather than the use of a known effective monotherapy such as doxorubicin.

Adjuvant radiation Radiation therapy induces programmed cell death in both normal and malignant lymphocytes. Given the sensitivity of malignant lymphocytes to radiation-induced injury, the efficacy of external beam, megavoltage radiation therapy has been evaluated for the adjuvant treatment of high-grade, multicentric lymphoma in dogs. In one study, 52 dogs were treated with a short course of induction chemotherapy (11 weeks), immediately followed by staged, half-body irradiation.²⁰ Radiation therapy was administered to cranial and caudal body halves for a total dose of 8 Gy, given in two fractions of 4 Gy on consecutive days with cobalt-60 photons and a three-week interval between halves. The side effects associated with half-body irradiation were generally mild and included reversible myelosuppression and gastrointestinal upset. In addition to the safety of combined chemotherapy and adjuvant radiation, the investigated protocol was therapeutically effective, with treated patients achieving a first median remission time of 311 days.²⁰ The findings of this study emphasize that long-lasting remissions can be achieved in dogs with lymphoma by using short treatment protocols that combine chemotherapy and radiation.
Nodal irradiation for chemoresistant lymphoma
Malignant lymphocytes expressing multidrug-resistant phenotypes are afforded a survival advantage when exposed to cytotoxic agents. Attempting to treat resistant lymphocyte clones, even with novel chemotherapeutic agents, still may result in disease progression. Because of the limitations of chemical cytotoxic agents, in conjunction with the inherent radiosensitivity of malignant lymphocytes, the use of total lymphoid irradiation (TLI) for confirmed chemoresistant lymphoma has been investigated. In one study, 11 dogs with confirmed multidrug-resistant lymphoma were treated with total nodal irradiation. A dose of 2 Gy given in six fractions over two weeks was administered to all affected peripheral lymph nodes. By the fourth radiation fraction, all treated lymph nodes had returned to normal size, and dogs treated with nodal irradiation survived for a median of 143 days.²¹ The results of this pilot study demonstrate that dogs with chemoresistant lymphoma may still appreciably benefit from alternative treatment options such as nodal irradiation.
TREATING FELINE LYMPHOMA
Systemic chemotherapy

TABLE 3. Summary of Selected Feline Lymphoma Protocols

Unlike canine lymphoma in which several innovative treatment options have been investigated, the treatment of cats with high-grade lymphoma has not markedly changed during the past decade. Several systemic chemotherapeutic protocols have been evaluated for treating feline lymphoma (Table 3). In general, with the institution of multiagent systemic chemotherapy, most (about 60% to 70%) cats will achieve complete remission, with median survival times approximating six to nine months.¹ Although the treatment of cats with lymphoma has not changed greatly over the past several years, it has been suggested that cats diagnosed with lymphoma are afforded with better quality-of-life scores and survival times, as compared with a decade ago. In part, this suggestion is based on the dramatic decrease in the number of cats infected with FeLV, a reported negative prognostic factor in cats with lymphoma.²²

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Floyd County newpspaper editor calls on readers to make lifestyle changes to address area's diabetes health crisis

The editor of an Eastern Kentucky newspaper has joined an advocacy group's call for residents in his county to make simple, healthy lifestyle changes, serving as an example of how local newspapers and community members can engage the public to confront poor health status of the area, which is often put on the back-burner despite alarming warning signs.

Recently, the Tri-County Diabetes Partnership declared the rate of diabetes in Floyd, Johnson and Magoffin counties (map) "a crisis of epidemic proportions." The rate in 2002-10, the latest available, was 14 percent.

If the federal Centers for Disease Control and Prevention "saw a similar increase in any other illness, they would probably declare a national emergency,” said J.D. Miller, vice president of medical affairs for Appalachian Regional Healthcare, who chaired the meeting.

The group's statement was an appropriate response to direct public's attention to the imperative of addressing the area's skyrocketing rate of the disease, Ralph Davis of The Floyd County Times wrote in an editorial.

Diabetes will remain a crisis unless we do something about it, said Davis, and "if you have been waiting for a crisis before making healthy lifestyle changes, we’ve got one for you. In fact, we have several," Davis said.

The Central Appalachian region suffers from disproportionate rates of diabetes, cancer and heart disease, and Floyd, Magoffin and Johnson counties have much higher rates of obesity than state and national averages, Davis notes. Floyd County ranks last among the state’s 120 counties in overall health measures, and Johnson and Magoffin counties are ranked 108th and 104th, respectively.

To do something about this problem, Davis calls for concentrated attention by health care providers and government officials, but the problem won't be solved without action from the community and individuals, he says. Simple, healthy lifestyle changes are needed.

"It’s going to require the conscious decision by everyone in the region to do what they can to improve their diet and exercise habits, and to encourage their friends and family to do the same," said Davis.

Calls like Davis's are needed even more in most of the counties that surround the three counties, based on data from the CDC's Behavioral Risk Surveillance System. The counties in dark blue had rates above 14 percent; the highest was Greenup, at 17 percent.

The editor of an Eastern Kentucky newspaper has joined an advocacy group's call for residents in his county to make simple, healthy lifestyle changes, serving as an example of how local newspapers and community members can engage the public to confront poor health status of the area, which is often put on the back-burner despite alarming warning signs.

Recently, the Tri-County Diabetes Partnership declared the rate of diabetes in Floyd, Johnson and Magoffin counties (map) "a crisis of epidemic proportions." The rate in 2002-10, the latest available, was 14 percent.

If the federal Centers for Disease Control and Prevention "saw a similar increase in any other illness, they would probably declare a national emergency,” said J.D. Miller, vice president of medical affairs for Appalachian Regional Healthcare, who chaired the meeting.

The group's statement was an appropriate response to direct public's attention to the imperative of addressing the area's skyrocketing rate of the disease, Ralph Davis of The Floyd County Times wrote in an editorial.

Diabetes will remain a crisis unless we do something about it, said Davis, and "if you have been waiting for a crisis before making healthy lifestyle changes, we’ve got one for you. In fact, we have several," Davis said.

The Central Appalachian region suffers from disproportionate rates of diabetes, cancer and heart disease, and Floyd, Magoffin and Johnson counties have much higher rates of obesity than state and national averages, Davis notes. Floyd County ranks last among the state’s 120 counties in overall health measures, and Johnson and Magoffin counties are ranked 108th and 104th, respectively.

To do something about this problem, Davis calls for concentrated attention by health care providers and government officials, but the problem won't be solved without action from the community and individuals, he says. Simple, healthy lifestyle changes are needed.

"It’s going to require the conscious decision by everyone in the region to do what they can to improve their diet and exercise habits, and to encourage their friends and family to do the same," said Davis.

Calls like Davis's are needed even more in most of the counties that surround the three counties, based on data from the CDC's Behavioral Risk Surveillance System. The counties in dark blue had rates above 14 percent; the highest was Greenup, at 17 percent.

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Thinking outside the (litter) box

Grigg EK, Pick L and Nibblett B. Litter box preference in domestic cats: covered versus uncovered. J Feline Med Surg. 2013; 15: 280-4.

The most common behavior problem in cats leading to their relinquishment to animal shelters is inappropriate elimination or housesoiling. In this situation, cats eliminate urine, feces, or both around the house, but outside the litter box. Litter box management is one area of focus for prevention of elimination disorders of either medical or behavioral origin. Some of the common recommendations associated with improving litter box management are: 

1) cleanliness – boxes should be cleaned at least once per day and litter completely replaced weekly,
2) type of litter – the fine-grained clumping clay litter is the most commonly recommended,
3) number of litter boxes – the general yet untested rule of the number of cats plus one,
4) litter box size – larger box size especially for larger cats and,
5) style of box – recommending against self-cleaning boxes or covered boxes. 

Little research has been done to look at box style, such as a preference for uncovered versus covered litter boxes. The authors wanted to determine if cats did prefer uncovered litter boxes when all other factors are equal. Twenty-eight cats were enrolled in the study. Nineteen of the cats showed no preference between a covered or uncovered box. Some individual cats did have preferences for one box type or the other – four cats for uncovered boxes, four cats for covered boxes. With a minority of cats exhibiting a litter box style preference, offering a ‘cafeteria’ choice of litter boxes, including a covered box, might be beneficial. Additional studies related to litter box management are recommended, such as evaluating scented versus unscented litters. [VT]

See also: Sung W and Crowell-Davis SL. Elimination behavior patterns of domestic cats (Felis catus) with and without elimination behavior problems. Am J Vet Res. 2006; 67: 1500-4.

More on cat health:
Winn Feline Foundation Library
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Grigg EK, Pick L and Nibblett B. Litter box preference in domestic cats: covered versus uncovered. J Feline Med Surg. 2013; 15: 280-4.

The most common behavior problem in cats leading to their relinquishment to animal shelters is inappropriate elimination or housesoiling. In this situation, cats eliminate urine, feces, or both around the house, but outside the litter box. Litter box management is one area of focus for prevention of elimination disorders of either medical or behavioral origin. Some of the common recommendations associated with improving litter box management are: 

1) cleanliness – boxes should be cleaned at least once per day and litter completely replaced weekly,
2) type of litter – the fine-grained clumping clay litter is the most commonly recommended,
3) number of litter boxes – the general yet untested rule of the number of cats plus one,
4) litter box size – larger box size especially for larger cats and,
5) style of box – recommending against self-cleaning boxes or covered boxes. 

Little research has been done to look at box style, such as a preference for uncovered versus covered litter boxes. The authors wanted to determine if cats did prefer uncovered litter boxes when all other factors are equal. Twenty-eight cats were enrolled in the study. Nineteen of the cats showed no preference between a covered or uncovered box. Some individual cats did have preferences for one box type or the other – four cats for uncovered boxes, four cats for covered boxes. With a minority of cats exhibiting a litter box style preference, offering a ‘cafeteria’ choice of litter boxes, including a covered box, might be beneficial. Additional studies related to litter box management are recommended, such as evaluating scented versus unscented litters. [VT]

See also: Sung W and Crowell-Davis SL. Elimination behavior patterns of domestic cats (Felis catus) with and without elimination behavior problems. Am J Vet Res. 2006; 67: 1500-4.

More on cat health:
Winn Feline Foundation Library
Find us on Facebook
Follow us on Twitter
Join us on Google+

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Veteran journalist offers advice on covering mental health issues: Be careful, creative, and balanced, not discriminatory

The term 'mental health' has been tossed around a lot lately in stories about Kentucky's mental health funding and mental health coverage through Medicaid expansion. It's important to use precise language when writing about the topic, because a fourth of Americans are affected by mental-health issues each year, and many  don't seek treatment due to its stigma.

"Fair, accurate and balanced portrayals of mental health in the news media are so important," says Melissa McCoy of the California Newspaper Publishers Association. She notes that studies show coverage of mental health is mostly reactive, responding to a school shooting or n act of violence, which could skew public perceptions about mental illness. She says journalists should "provide accurate coverage of mental health without adding to its stigma" or to the discrimination faced by those with mental illness.

Journalists can seek balance by asking themselves about the relevance of mental health to the story and making sure to use the right type of language, says McCoy; be creative about mental health coverage by integrating it into stories about general health, veterans returning from war, substance abuse recovery, unemployment or even stress among students. 

The term 'mental health' has been tossed around a lot lately in stories about Kentucky's mental health funding and mental health coverage through Medicaid expansion. It's important to use precise language when writing about the topic, because a fourth of Americans are affected by mental-health issues each year, and many  don't seek treatment due to its stigma.

"Fair, accurate and balanced portrayals of mental health in the news media are so important," says Melissa McCoy of the California Newspaper Publishers Association. She notes that studies show coverage of mental health is mostly reactive, responding to a school shooting or n act of violence, which could skew public perceptions about mental illness. She says journalists should "provide accurate coverage of mental health without adding to its stigma" or to the discrimination faced by those with mental illness.

Journalists can seek balance by asking themselves about the relevance of mental health to the story and making sure to use the right type of language, says McCoy; be creative about mental health coverage by integrating it into stories about general health, veterans returning from war, substance abuse recovery, unemployment or even stress among students. 

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Pike County settles its part of Oxycontin lawsuit against Purdue Pharma for $4 million; state remains a plaintiff

Officials of Pike County, Kentucky, announced this week that Purdue Pharma, the maker of OxyContin, will pay $4 million to settle the county's part of a lawsuit the county and state filed in 2007 seeking damages for the addiction OxyContin caused "after the company aggressively marketed it to doctors as a safe option for pain relief," Russ Cassady reports for the Appalachian News-Express in Pikeville.

The state remains a plaintiff in the suit, which  is largely based on admissions of guilt made by the company and several top-ranking company officials in a May 2007 Virginia federal court settlement. Purdue Pharma, its president, chief legal counsel and former medical director pleaded guilty to misleading doctors, regulators and patients about OxyContin during that case.

The nation's prescription-drug epidemic apparently began in Central Appalachia, largely because of the introduction and high rate of prescription of OxyContin. The lawsuit sought reimbursement for drug-abuse programs, law-enforcement actions and prescription payments through Medicaid and the Kentucky Pharmaceutical Alliance Program. The local officials indicated the settlement could increase the size of a planned rehabilitation facility for people convicted of drug charges.

Officials of Pike County, Kentucky, announced this week that Purdue Pharma, the maker of OxyContin, will pay $4 million to settle the county's part of a lawsuit the county and state filed in 2007 seeking damages for the addiction OxyContin caused "after the company aggressively marketed it to doctors as a safe option for pain relief," Russ Cassady reports for the Appalachian News-Express in Pikeville.

The state remains a plaintiff in the suit, which  is largely based on admissions of guilt made by the company and several top-ranking company officials in a May 2007 Virginia federal court settlement. Purdue Pharma, its president, chief legal counsel and former medical director pleaded guilty to misleading doctors, regulators and patients about OxyContin during that case.

The nation's prescription-drug epidemic apparently began in Central Appalachia, largely because of the introduction and high rate of prescription of OxyContin. The lawsuit sought reimbursement for drug-abuse programs, law-enforcement actions and prescription payments through Medicaid and the Kentucky Pharmaceutical Alliance Program. The local officials indicated the settlement could increase the size of a planned rehabilitation facility for people convicted of drug charges.

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Stroke Risk Greatly Increases With Drinking Soda

   Drinking Soda Increases Stroke Chance

It doesn't matter whether it's sugary or diet: High consumption of carbonated soft drinks significantly increases your risk of stroke, research shows.

Researchers found that those with higher consumptions of both sugar-sweetened and low-calorie soda were significantly more likely to suffer from strokes.


"Greater consumption of sugar-sweetened and low-calorie sodas was associated with a significantly higher risk of stroke," the researchers wrote. "This risk may be reduced by substituting alternative beverages for soda."

Read The Whole Soda Causes Stroke Story Here

   Drinking Soda Increases Stroke Chance

It doesn't matter whether it's sugary or diet: High consumption of carbonated soft drinks significantly increases your risk of stroke, research shows.

Researchers found that those with higher consumptions of both sugar-sweetened and low-calorie soda were significantly more likely to suffer from strokes.


"Greater consumption of sugar-sweetened and low-calorie sodas was associated with a significantly higher risk of stroke," the researchers wrote. "This risk may be reduced by substituting alternative beverages for soda."

Read The Whole Soda Causes Stroke Story Here

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Antibiotics Cause Long Term Damage To Good Gut Bacteria

Gut Biota Never Recover from Antibiotics: Damages Future Generations

The misuse of antibiotics is not only causing new, never-before known diseases like E. coli and MRSA, the flesh-eating bacteria, it's also destroying the gut biome with devastating effects on our ability to deal with infections and destroying our ability to absorb nutrients from food.

Emerging research shows that the harmful effects of antibiotics go much further than the development of drug resistant diseases. The beneficial bacteria lost...Read More HERE

Gut Biota Never Recover from Antibiotics: Damages Future Generations

The misuse of antibiotics is not only causing new, never-before known diseases like E. coli and MRSA, the flesh-eating bacteria, it's also destroying the gut biome with devastating effects on our ability to deal with infections and destroying our ability to absorb nutrients from food.

Emerging research shows that the harmful effects of antibiotics go much further than the development of drug resistant diseases. The beneficial bacteria lost...Read More HERE

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