Toxic effects and antitumor response of gemcitabine in combination with piroxicam treatment in dogs with transitional cell carcinoma of the urinary bladder

Marconato, Laura; Zini, Eric; Lindner, Donna; Suslak-Brown, Lisa; Nelson, Victoria; Jeglum, Ann K

doi:10.2460/javma.238.8.1004

Cited by 43 publications

(47 citation statements)

References 38 publications

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“…55 Carboplatin, a platinum drug with less renal toxicity, was combined with piroxicam. 58 The reported tumor responses included two (5%) CR, eight (21%) PR, and 19 (50%) SD. 56 In a recent study, gemcitabine (800 mg/m 2 ) and piroxicam were given to dogs with cytologic evidence of TCC or biopsy-confirmed TCC.…”

Section: Prognosismentioning

confidence: 98%

Tumors of the Urinary System

Knapp¹,

McMillan²

2013

Withrow and MacEwen's Small Animal Clinical Oncology

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Section: Prognosismentioning

confidence: 98%

Tumors of the Urinary System

Knapp¹,

McMillan²

2013

Withrow and MacEwen's Small Animal Clinical Oncology

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“…The PFI in dogs with TCC treated with cisplatin alone is 75–84 and is 124 days when combined with piroxicam 17, 18. Multiple other chemotherapeutic agents have been described for the treatment of TCC in dogs and response rates to cisplatin, doxorubicin, mitomycin C, gemcitabine, vinblastine, and chlorambucil range from 3 to 71% with PFI ranging from 75 to 329 days 10, 16, 17, 18, 19, 20, 21, 22, 23…”

mentioning

confidence: 99%

Randomized Phase III Trial of Piroxicam in Combination with Mitoxantrone or Carboplatin for First‐Line Treatment of Urogenital Tract Transitional Cell Carcinoma in Dogs

Allstadt

Rodríguez

Boostrom

et al. 2015

Veterinary Internal Medicne

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BackgroundReported response rates of transitional cell carcinoma (TCC) in dogs to piroxicam in combination with either mitoxantrone or carboplatin are similar; however, it is unknown whether either drug might provide superior duration of response.Hypothesis/ObjectivesTo determine if the progression‐free interval (PFI) of dogs with TCC treated with mitoxantrone and piroxicam was different than that of dogs receiving carboplatin and piroxicam. The hypothesis was that the efficacy of mitoxantrone is no different from carboplatin.AnimalsFifty dogs with TCC without azotemia.MethodsProspective open‐label phase III randomized study. Either mitoxantrone or carboplatin was administered every 3 weeks concurrently with piroxicam with restaging at 6‐week intervals. Twenty‐four dogs received carboplatin and 26 received mitoxantrone.ResultsResponse was not different between groups (P = .56). None of the dogs showed complete response. In the mitoxantrone group, there were 2 (8%) partial responses (PR) and 18 (69%) dogs with stable disease (SD). In the carboplatin group, there were 3 PR (13%) and 13 (54%) dogs with SD. The PFI was not significantly different between groups (mitoxantrone = 106 days; carboplatin = 73.5 days; P = .62; hazard ratio 0.86; 95% confidence interval 0.47–1.56). Dogs with prostatic involvement experienced a shorter survival (median, 109 days) compared to dogs with urethral, trigonal, or apically located tumors; this difference was significant (median 300, 190, and 645 days, respectively; P = .005).Conclusions and Clinical ImportanceThis study did not detect a different in outcome in dogs with TCC treated with either mitoxantrone or carboplatin in combination with piroxicam.

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“…This implies that NPX may be particularly applicable for use in urinary bladder cancer. Piroxicam has shown therapeutic efficacy in urinary bladder cancer in dogs (24–26). The use of NPX which preferentially accumulates in urine in humans (27) might allow the use of a lower dose with more limited gastric toxicity than would be required with piroxicam.…”

Section: Discussionmentioning

confidence: 99%

Prevention of Chemically Induced Urinary Bladder Cancers by Naproxen: Protocols to Reduce Gastric Toxicity in Humans Do Not Alter Preventive Efficacy

Lubet

Scheiman

Bode

et al. 2015

Cancer Prevention Research

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The COX inhibitors (NSAIDs/Coxibs) are a major focus for the chemoprevention of cancer. The COX-2 specific inhibitors have progressed to clinical trials, and have shown preventive efficacy in colon and skin cancers. However, they have significant adverse cardiovascular (CV) effects. Certain NSAIDs (e.g., naproxen (NPX)] have a good cardiac profile, but can cause gastric toxicity. The present studies examined protocols to reduce this toxicity of NPX. Female Fischer-344 rats were treated weekly with the urinary bladder specific carcinogen hydroxybutyl(butyl)nitrosamine (OH-BBN) for 8 weeks. Rats were dosed daily with NPX (40 mg/Kg BW/day, gavage) or with the proton pump inhibitor omeprazole (4.0 mg/Kg BW/day) either singly or in combination beginning 2 weeks after the final OH-BBN. OH-BBN treated rats, 96% developed urinary bladder cancers. While omeprazole alone was ineffective (97% cancers), NPX alone or combined with omeprazole prevented cancers; yielding 27 and 35% cancers, respectively. In a separate study, OH-BBN treated rats were administered NPX: (A) daily, (B) 1 week daily NPX/1wk vehicle, (C) 3 weeks daily NPX/3 week vehicle, or (D) daily vehicle beginning 2 weeks after last OH-BBN treatment. In the intermittent dosing study, protocol A, B, C and D resulted in palpable cancers in 27%, 22%, 19% and 96% of rats (P<0.01). Short-term NPX treatment increased apoptosis, but did not alter proliferation in the urinary bladder cancers. Two different protocols which should decrease the gastric toxicity of NSAIDs in humans did not alter chemopreventive efficacy. This should encourage the use of NSAIDs (e.g. NPX) in clinical prevention trials.

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Toxic effects and antitumor response of gemcitabine in combination with piroxicam treatment in dogs with transitional cell carcinoma of the urinary bladder

Cited by 43 publications

References 38 publications

Tumors of the Urinary System

Tumors of the Urinary System

Randomized Phase III Trial of Piroxicam in Combination with Mitoxantrone or Carboplatin for First‐Line Treatment of Urogenital Tract Transitional Cell Carcinoma in Dogs

Prevention of Chemically Induced Urinary Bladder Cancers by Naproxen: Protocols to Reduce Gastric Toxicity in Humans Do Not Alter Preventive Efficacy

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