CCNU in the Treatment of Canine Epitheliotropic Lymphoma

Williams, Laurel E.; Rassnick, Kenneth M.; Power, Helen T.; Lana, Susan E.; Morrison-Collister, Kirsten E.; Hansen, Katherine; Johnson, Jeffrey L.

doi:10.1111/j.1939-1676.2006.tb02833.x

Cited by 72 publications

(105 citation statements)

References 34 publications

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“…Other common adverse effects included hepatic and gastrointestinal toxicities, which were not unexpected based on the combination of drugs used in this protocol. Lomustine is known to cause hepatotoxicity in dogs, with reported rates of 83–86% . Twenty‐four dogs (59%) developed increases in ALT activity during this study, with 9 dogs having grade 3 or 4 increases.…”

Section: Discussionmentioning

confidence: 71%

Pulse‐Administered Toceranib Phosphate Plus Lomustine for Treatment of Unresectable Mast Cell Tumors in Dogs

Burton

Venable

Vail

et al. 2015

Veterinary Internal Medicne

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BackgroundNonresectable mast cell tumors (MCT) in dogs remain a therapeutic challenge, and investigation of novel combination therapies is warranted. Intermittent administration of tyrosine kinase inhibitors (TKI) combined with cytotoxic chemotherapy may effectively chemosensitize canine MCT while decreasing cost and adverse effects associated with either agent administered as monotherapy.Hypothesis/ObjectivesThe primary study objectives were to (1) identify the maximally tolerated dose (MTD), (2) determine the objective response rate (ORR) and (3) describe the adverse event profile of pulse‐administered toceranib phosphate (TOC) combined with lomustine.AnimalsForty‐seven client‐owned dogs with measurable MCT.MethodsToceranib phosphate was given PO on days 1, 3 and 5 of a 21‐day cycle at a target dosage of 2.75 mg/kg. Lomustine was given PO on day 3 of each cycle at a starting dosage of 50 mg/m2. All dogs were concurrently treated with diphenhydramine, omeprazole, and prednisone.ResultsThe MTD of lomustine was established at 50 mg/m2 when combined with pulse‐administered TOC; the dose‐limiting toxicity was neutropenia. Forty‐one dogs treated at the MTD were evaluable for outcome assessment. The ORR was 46% (4 complete response, 15 partial response) and the overall median progression‐free survival (PFS) was 53 days (1 to >752 days). On multivariate analysis, variables significantly associated with improved PFS included response to treatment, absence of metastasis, and no previous chemotherapy.Conclusions and clinical importanceCombined treatment with pulse‐administered TOC and lomustine generally is well tolerated and may be a reasonable treatment option for dogs with unresectable or metastatic MCT.

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Section: Discussionmentioning

confidence: 71%

Pulse‐Administered Toceranib Phosphate Plus Lomustine for Treatment of Unresectable Mast Cell Tumors in Dogs

Burton

Venable

Vail

et al. 2015

Veterinary Internal Medicne

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“…Hosoya et al 10 reported on 109 dogs treated with CCNU for a variety of cancers and found that 83% developed some increase in ALT activity over their starting result. Williams et al 2 reported on 36 dogs with cutaneous LSA treated with CCNU and found that 60% of dogs tested after treatment had increases in ALT activity, and 86% of dogs that had more than 1 dose of CCNU had increases in ALT activity. Given the high incidence of increases in liver enzyme activity in dogs receiving CCNU and the acute onset of severe increases noted in some patients, frequent liver‐specific laboratory testing should be considered during CCNU‐based therapy in these dogs.…”

Section: Discussionmentioning

confidence: 99%

Prospective Randomized Clinical Trial Assessing the Efficacy of Denamarin for Prevention of CCNU‐Induced Hepatopathy in Tumor‐Bearing Dogs

Skorupski

Hammond

Irish

et al. 2011

Veterinary Internal Medicne

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Background: Increases in liver enzymes occur in up to 86% of dogs receiving CCNU and can result in treatment delay or early discontinuation of treatment. Denamarin contains S-adenosylmethionine and silybin, both of which have been investigated as treatments for various liver diseases.Hypothesis: Dogs on CCNU receiving Denamarin have lower alanine aminotransferase (ALT) activity than dogs not receiving Denamarin. Dogs on Denamarin are less likely to require treatment delay because of hepatopathy and are more likely to complete their prescribed course of CCNU.Animals: Dogs with lymphoma, mast cell tumor, or histiocytic sarcoma that were prescribed CCNU with or without corticosteroids and with normal ALT activity were eligible for enrollment.Methods: Dogs were prospectively randomized to receive either concurrent Denamarin during CCNU chemotherapy or to receive CCNU alone. Liver-specific laboratory tests were run before each dose of CCNU.Results: Increased liver enzyme activity occurred in 84% of dogs receiving CCNU alone and in 68% of dogs on concurrent Denamarin. Dogs receiving CCNU alone had significantly greater increases in ALT, aspartate aminotransferase, alkaline phosphatase, and bilirubin and a significantly greater decrease in serum cholesterol concentrations than dogs receiving concurrent Denamarin. Dogs receiving CCNU alone were significantly more likely to have treatment delayed or discontinued because of increased ALT activity.Conclusions: Increased liver enzyme activity occurs commonly in dogs receiving CCNU chemotherapy. These results support the use of concurrent Denamarin to minimize increased liver enzyme activity in dogs receiving CCNU chemotherapy. Denamarin treatment also increases the likelihood of dogs completing a prescribed CCNU course.

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“…Moreover, previous studies reported that lomustine can be considered for the treatment of canine lymphoma in dogs [40], [41], [42], [43], although it induced common but not life-threatening toxicity [44].…”

Section: Discussionmentioning

confidence: 99%

Prediction of Cancer Drugs by Chemical-Chemical Interactions

Lü

Huang

et al. 2014

PLoS ONE

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Cancer, which is a leading cause of death worldwide, places a big burden on health-care system. In this study, an order-prediction model was built to predict a series of cancer drug indications based on chemical-chemical interactions. According to the confidence scores of their interactions, the order from the most likely cancer to the least one was obtained for each query drug. The 1st order prediction accuracy of the training dataset was 55.93%, evaluated by Jackknife test, while it was 55.56% and 59.09% on a validation test dataset and an independent test dataset, respectively. The proposed method outperformed a popular method based on molecular descriptors. Moreover, it was verified that some drugs were effective to the ‘wrong’ predicted indications, indicating that some ‘wrong’ drug indications were actually correct indications. Encouraged by the promising results, the method may become a useful tool to the prediction of drugs indications.

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CCNU in the Treatment of Canine Epitheliotropic Lymphoma

Cited by 72 publications

References 34 publications

Pulse‐Administered Toceranib Phosphate Plus Lomustine for Treatment of Unresectable Mast Cell Tumors in Dogs

Pulse‐Administered Toceranib Phosphate Plus Lomustine for Treatment of Unresectable Mast Cell Tumors in Dogs

Prospective Randomized Clinical Trial Assessing the Efficacy of Denamarin for Prevention of CCNU‐Induced Hepatopathy in Tumor‐Bearing Dogs

Prediction of Cancer Drugs by Chemical-Chemical Interactions

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