Piroxicam Therapy Research Articles

Ultrasonographic assessment of transitional cell carcinoma of the urinary bladder in dogs: a perspective of tumor size change

Study purposes were to evaluate ultrasonographic characteristics of transitional cell carcinoma (TCC) and quantitate bladder tumor size in dogs. Heterogeneous mass, wall involvement, and broad-based attachment were significantly associated with TCC, but not prominently the trigone region. Mass size evaluation revealed a significant correlation between progressive disease (PD) in TCC patients with piroxicam therapy. Largest diameter of target lesion/ body weight (cm/kg) ratio showed a high mean value in PD. A value > 0.3 was associated with PD with 83% sensitivity and 66% specificity. The results suggest that ultrasonography can provide evidence for diagnosing and predicting a prognosis for TCC.

Clinical outcome of partial cystectomy for transitional cell carcinoma of the canine bladder.

Canine transitional cell carcinoma (TCC) of the bladder has historically been treated with a combination of chemotherapy, cyclooxygenase inhibitors and radiation therapy. While surgery has been used to treat TCC of the bladder, its efficacy has yet to be established. Thirty-seven client owned dogs that underwent partial cystectomy +/- various nonsurgical treatments for TCC were retrospectively evaluated. The overall median progression-free interval (PFI) was 235 days and the median survival time (ST) was 348 days. Prognostic factors identified on univariate analysis significant for ST were age, tumor location, full thickness excision and frequency of piroxicam administration. Prognostic factors significant for PFI were full thickness excision and frequency of piroxicam administration. The median ST with partial cystectomy and daily piroxicam therapy, with or without chemotherapy, was 772 days. Dogs with non-trigonal bladder TCC treated with full thickness partial cystectomy and daily piroxicam (+/- chemotherapy) may have improved outcome compared to dogs treated with medical therapy.

Risk factors for treatment-related adverse events in cancer-bearing dogs receiving piroxicam.

Piroxicam has antitumour effects in dogs with cancer, although side effects may limit its use. The purpose of this study was to retrospectively identify factors predisposing cancer-bearing dogs to adverse events (AEs) following piroxicam therapy. Medical records of dogs presented to the Purdue Veterinary Teaching Hospital between 2005 and 2015 were reviewed, and 137 dogs met the criteria for study inclusion. Toxic effects of piroxicam in these dogs were graded according to an established system. Multivariate logistic regression was used to estimate the extent to which certain factors affected the risk for AEs. Age [odds ratio (OR) 1.250, P = 0.009; 95% confidence interval (CI) 1.057-1.479] and concurrent use of gastroprotectant medications (OR 2.612, P = 0.025; 95% CI 1.127-6.056) significantly increased the risk for gastrointestinal AEs. The results of this study may help inform the risk versus benefit calculation for clinicians considering the use of piroxicam to treat dogs with cancer.

Comparison of effects of preoperative piroxicam and ibuprofen on pain after separator placement: A randomized controlled trial

Introduction: Orthodontic therapy causes significant pain for a large percentage of patients. It is one of the main reasons that discourage patients from seeking orthodontic treatment. Pain during orthodontic treatment may have a negative influence on cooperation and can also reduce the compliance. This study assessed the effectiveness of a single dose of preoperative Piroxicam in reducing the incidence and severity of pain after orthodontic separator placement when compared to ibuprofen. Materials and Methods: The study was a randomized, placebo-controlled, double-blind, parallel-arm study. Sixty eight patients were recruited for this study and were randomly assigned to one of the three experimental groups: 1. 20 mg of Piroxicam followed by two doses of multivitamin placebo ( n = 30); 2. 400 mg of Ibuprofen in three doses ( n = 20) and 3. A multivitamin placebo ( n = 18). All the three groups were administered the first dose of the respective medication one hour prior to separator placement, the successive two doses were given at 3 hours and 7 hours after separator placement. The pain experienced by the patient was assessed at the time intervals 2 hours, 4 hours, 6 hours, bedtime, on awakening the following day and 24 hours after administration using a visual analogue scale. Results: A comparison of pain perception between all three groups with the repeated measures analysis of variance (ANOVA) and a comparison of pain perception between the first and second group using the Student t test revealed that preemptive Piroxicam therapy significantly lower pain levels experienced at all-time intervals starting from 2 hours after separator placement till 24 hours after placement. Conclusion: A single dose of Piroxicam taken 60 minutes before separator placement reduces pain due to separator placement experienced in the first 24 hours following separator placement.

Evaluation of adverse events in cats receiving long-term piroxicam therapy for various neoplasms.

The role of cyclo-oxygenase 2 (COX-2) and prostaglandins (PG) in carcinogenesis has been documented in many species. Piroxicam has shown efficacy against several neoplasms and is frequently prescribed for chronic use. There are no studies investigating chronic piroxicam administration in cats and the chronic use of non-steroidal anti-inflammatory agents in this species has long been cautioned against. This retrospective study aimed to evaluate adverse effects in cats receiving long-term daily piroxicam. Seventy-three cats received daily piroxicam at doses of 0.13-0.41mg/kg. Treatment duration ranged from 1 to 38 months. Treatment with piroxicam was found to significantly increase frequency of vomiting during the first month of therapy, though this was most significant for cats receiving concurrent chemotherapy. Piroxicam administration was not significantly associated with hematologic, renal or hepatic toxicities. Adverse events were not correlated with dosage. Adverse events were reported in 29% of cats, and were generally mild and transient. Eight percent discontinued piroxicam due to adverse reaction, and 4% due to difficult administration. This study indicates that long-term daily piroxicam is generally well tolerated in cats at conventional doses.

Metronomic Therapy with Cyclophosphamide and Piroxicam Effectively Delays Tumor Recurrence in Dogs with Incompletely Resected Soft Tissue Sarcomas

Continuous administration of low doses of cyclophosphamide and standard doses of cyclooxygenase-inhibiting drugs has been shown to suppress tumor angiogenesis, reverse immunosuppression, and deplete regulatory T cells in cancer models. We hypothesized that continuous treatment with low-dose cyclophosphamide and full-dose piroxicam would delay tumor recurrence in dogs with soft tissue sarcomas (STS). Eighty-five dogs with incompletely resected STS, 30 treated dogs, and 55 contemporary control dogs. Treatment outcomes in 85 dogs with incompletely resected STS were evaluated in a retrospective study. Dogs in the treatment group received continuously administered low-dose cyclophosphamide (10 mg/m2) and standard dose piroxicam (0.3 mg/kg) therapy. Time to local tumor recurrence (disease-free interval; DFI) was compared between the 30 treated dogs and 55 untreated control dogs matched for age and tumor site and grade. DFI was significantly (P < .0001) prolonged for STS of all sites (trunk and extremity) in treated dogs compared with untreated control dogs. The DFI also was significantly longer in treated dogs when tumor site (trunk and extremity) was compared. Twelve treated dogs (40%) experienced mild toxicity (grade 1 and 2) at some point during treatment and 1 dog developed grade 4 cystitis. Every other day dosing was tolerated better than daily dosing. Metronomic therapy with cyclophosphamide and piroxicam was very effective in preventing tumor recurrence in dogs with incompletely resected STS. These findings suggest that further evaluation of this approach is warranted as adjuvant therapy in dogs with highly metastatic tumors such as osteosarcoma and melanoma.

Carboplatin and piroxicam therapy in 31 dogs with transitional cell carcinoma of the urinary bladder

Invasive transitional cell carcinoma (TCC) of the urinary bladder responds poorly to medical therapy. Combining platinum chemotherapy with a cyclooxygenase (cox) inhibitor has shown promise against canine TCC, where the disease closely mimics the human condition. A phase II clinical trial of carboplatin combined with the cox inhibitor, piroxicam, was performed in 31 dogs with naturally occurring, histopathologically confirmed, measurable TCC. Complete tumour staging was performed before and at 6-week intervals during therapy. Tumour responses in 29 dogs included 11 partial remissions, 13 stable disease and five progressive disease. Two of the 31 dogs were withdrawn prior to the re-staging of the tumour. Gastrointestinal toxicity was observed in 23 dogs. Hematologic toxicity was noted in 11 dogs. The median survival was 161 days from first carboplatin treatment to death. In conclusion, carboplatin/piroxicam induced remission in 40% of dogs providing evidence that a cox inhibitor enhances the antitumour activity of carboplatin. The frequent toxicity and limited survival, however, do not support the use of this specific protocol against TCC.

Antitumor effects of piroxicam in spontaneous canine invasive urinary bladder cancer, a relevant model of human invasive bladder cancer.

Invasive urinary bladder cancer results in >12,000 deaths each year in the US alone. More effective forms of therapy are needed to treat this cancer. Our interest in the antitumor activity of nonsteroidal antiinflammatory drugs (NSAIDs) began when we observed unexpected remission of naturally-occurring cancer in pet dogs who were receiving the NSAID piroxicam for pain relief. These observations led to phase I and II clinical trials of piroxicam in pet dogs with spontaneous cancer.1,2Gastrointestinal toxicity was dose limiting, but remission occurred at lower, less toxic doses.’ Invasive transitional cell carcinoma of the urinary bladder (TCC) was one of the forms of canine cancer that underwent remission with piroxicam therapy.2This finding is of particular interest because naturally-occurring canine TCC is very similar to human invasive urinary bladder cancer in histopathologic characteristics, biological behavior, and response to chemotherapy.3Canine TCC is a heterogenous, chemoresistant solid tumor with <20% of cases responding to single agent chemotherapy.3

Ulcerative esophagitis and stricture due to long-term piroxicam therapy

Ulcerative esophagitis and stricture due to long-term piroxicam therapy

Efficacy and Tolerability of Intramuscular and Oral Meloxicam in Patients with Acute Lumbago: A Comparison with Intramuscular and Oral Piroxicam

SummaryIn this controlled, randomised, parallel-group, multicentre study, the efficacy and tolerability of an intramuscular (i.m.) dose of meloxicam (15 mg) on Day 1 followed by seven days of oral meloxicam (15 mg/day) were compared with those of an i.m. dose of piroxicam (20 mg) on Day 1 followed by seven days of oral piroxicam (20 mg/day) therapy in a total of 169 outpatients with acute lumbago. Time to onset of analgesic action after i.m. injection was determined, and overall efficacy, pain on movement, limitation of daily activities, local tolerability at the injection site and overall tolerability were assessed by investigators and patients on verbal rating scales (VRSs). Adverse events and laboratory assessments were documented. Meloxicam and piroxicam showed a rapid onset of action after i.m. injection (40 and 45 minutes median time, respectively), overall efficacy of both therapies was highly rated, and limitations to daily life were greatly reduced in the majority of patients in both groups. There were no statistically significant differences in efficacy between meloxicam and piroxicam. Local and overall tolerabilities were equally good for the two drugs, but there were fewer gastrointestinal (GI) adverse events among meloxicam patients (1.2% of patients) than piroxicam patients (7.0% of patients). The improved tolerability profile of meloxicam may be explained by its selectivity towards cyclooxygenase-2 (COX-2).

Inhibition of Growth of a Murine Squamous Cell Carcinoma by a Cyclooxygenase Inhibitor Increases Leukotriene B4 Production

To determine the role of metabolites of arachidonic acid in the growth of squamous cell carcinomas of the head and neck. Investigation of the effect of a cyclooxygenase inhibitor, piroxicam, on the growth of squamous cell carcinoma in a murine model. C3H/HeJ mice bearing squamous cell carcinoma (SCCVII) were treated with piroxicam (0.08 mg/d, orally) for 30 days beginning 1 day before tumor inoculation. Decrease in tumor volumes and tumor growth rates. Significant inhibition of tumor growth (P = .002) and final tumor weight (P = .0007) was noted in the group receiving piroxicam therapy. Prostaglandin E2 levels in the tumor tissue were unrelated to treatment or tumor size. Increased levels of leukotriene B4 were observed in the piroxicam-treated group (P = .03), and larger tumors were associated with decreased leukotriene B4 levels (P = .0001). Cyclooxygenase inhibitors may be effective in the treatment of some squamous cell carcinomas. The therapeutic effect of cyclooxygenase inhibitors may result from shunting into the lipoxygenase pathway of arachidonic acid metabolism.

Nonsteroidal Anti-Inflammatory Drug-Induced Enteropathy: Case Discussion and Review of the Literature

Nonsteroidal Anti-Inflammatory Drug-Induced Enteropathy: Case Discussion and Review of the Literature

Efficacy and tolerability of long-term tenoxicam versus piroxicam in patients with rheumatoid arthritis or osteoarthritis

The efficacy and tolerability of long-term tenoxicam and piroxicam therapy were compared in patients with rheumatoid arthritis or degenerative osteoarthritis. Sixty consecutive patients were randomized to receive treatment with either oral tenoxicam or piroxicam; 30 patients had rheumatoid arthritis and 30 had osteoarthritis. Both drugs were given in a single daily dose of 20 mg for 12 months, and all patients enrolled in the study were evaluated for efficacy and tolerability on a monthly basis. The efficacy and tolerability of once-daily tenoxicam were found to be comparable to that of once-daily piroxicam therapy. Greater clinical improvement in the symptoms of rheumatoid arthritis and osteoarthritis was noted in the tenoxicam-treated patients.

Piroxicam Plasma Concentrations Following Repeated Topical Application of a Piroxicam 0.5% Gel

The pharmacokinetic parameters of a piroxicam 0.5% topical gel were determined in 20 healthy volunteers (6 women and 14 men) following application of multiple doses (20mg piroxicam daily) over 14 days. 21 blood samples were drawn from each patient beginning just before application of the first dose, with the final sample taken 14 days after application of the last dose. Plasma concentrations of piroxicam were determined by high-performance liquid chromatography using UV detection at 340nm. There was considerable interindividual variation in piroxicam half-lives with a mean of 79 hours. Mean piroxicam plasma concentrations at steady-state were between 300 and 400 ng/ml, which is about 5% of those observed after equivalent doses of oral or intramuscular piroxicam. No adverse experiences were reported during the study period. Thus, the results of this study confirm the minimal systemic absorption of piroxicam during multiple-dose application of the 0.5% topical gel and the excellent tolerability of this mode of piroxicam therapy.

Are leucocyte‐derived free radicals involved in ischaemia in human legs?

Leucocyte-derived free radicals were monitored in 30 stage II peripheral vascular disease (PVD) patients in an open placebo-controlled study. Linked to a transcutaneous oxygen pressure (TcPO2) monitor, they performed two consecutive standard treadmill tests (5 min, 2 km h-1, 12% slope) before and after 15-days treatment with placebo or a leucocyte-derived free radical scavenger (Piroxicam, 20 mg day-1), the second test being carried out at the TcPO2 half-recovery time. Blood samples were collected at baseline, at the maximum walking times and the TcPO2 half recovery times. The total and differential leucocyte counts, the percentage of cells with pseudopodia or cytoplasmatic irregularities, the filterability rates (using a positive pressure Nuclepore filter system) of the main leucocyte subfractions and plasma oxidant activity were monitored. Compared with values before treatment and with the placebo-treated group Piroxicam therapy significantly (P less than 0.001) reduced the final half-recovery time, the percentage of cells with pseudopodia and the level of plasma oxidant activity (P less than 0.01) and kept the granulocyte filterability rate stable, showing leucocyte-derived free radicals are involved in peripheral ischaemia.

Impairment of human antipyrine metabolism by piroxicam

The pharmacokinetics of a single oral dose of antipyrine was determined in healthy young volunteers (18-28 years), both 3 days before piroxicam, ketoprofen, or naproxen administration and on the following day of their discontinuation. In all subjects treated with piroxicam (10, 20, and 40 mg daily) for 5 consecutive days, the rate of salivary antipyrine elimination slowed. Antipyrine half-life was prolonged and metabolic clearance was reduced significantly (p less than 0.01) proportional to the dose administered. After piroxicam was discontinued, both pharmacokinetic parameters of antipyrine returned toward normal. No significant modification in antipyrine half-life or metabolic clearance rate was demonstrated after pretreatment with ketoprofen (50, 100, and 200 mg daily) or naproxen (250 and 500 mg daily). The impairment on antipyrine disposition produced by piroxicam has been interpreted as a consequence of a reduction in the activity of hepatic microsomal drug-metabolizing enzymes, particularly the cytochrome P-450 system. These results suggest the possibility of drug accumulation and toxicity when certain other therapeutic agents are administered simultaneously with piroxicam. For the same reason, it is recommended to bear in mind the potential danger of long-term piroxicam therapy on the oxidative degradation of steroid hormones and other endogenous compounds that are metabolized by the mixed-function oxidase system.

Effect of piroxicam therapy on granulocyte function and granulocyte elastase concentration in peripheral blood and synovial fluid of rheumatoid arthritis patients

The effect of piroxicam therapy (20 mg/day for 15 days) on various polymorphonuclear granulocyte (PMN) responses and on PMN elastase concentration was investigated in nine patients with active rheumatoid arthritis. Peripheral blood and synovial fluid samples were collected before starting therapy and 12 h after the last dose of the drug. All patients were evaluable for peripheral blood analysis and six for synovial fluid analysis. Piroxicam therapy had no effect on PMN random migration and phagocytosis, while it significantly reduced both FMLP-induced aggregation and FMLP-induced chemotaxis. This seems mainly due to an effect on FMLP binding, as no differences were observed after therapy in PMA- and PHA-induced aggregation as well as in serum-induced chemotaxis. In contrast, a marked impairment of NBT test and PMA- and FMLP-induced superoxide anion (O2-) production was found after piroxicam therapy. This effect was as evident in peripheral blood as in synovial fluid PMN. Also, a significant reduction in synovial fluid PMN number and synovial fluid PMN elastase concentration (elastase-alpha 1-proteinase complex) was found after treatment. It is concluded that piroxicam may act at different sites on various PMN responses. Its effect on O2- generation and PMN elastase concentration in synovial fluid may have an important role in reducing destruction of arthritic joint tissue.

International experience with etodolac therapy for rheumatoid arthritis: An interim report of comparative efficacy

Etodolac, a nonsteroidal anti-inflammatory drug (NSAID) of the pyranocarboxylic acid family, has been tested in international clinical trials as a therapy for rheumatoid arthritis (RA). Preliminary results of 8- to 12-week double-blind trials indicate that etodolac therapy (200 mg twice a day) compared favorably with piroxicam therapy (20 mg once a day) and diclofenac therapy (50 mg three times a day) as measured by improvement in scores of five efficacy assessments: number of painful joints, number of swollen joints, physician's global assessment, patient's global assessment, and pain intensity. Etodolac also was as effective as naproxen (500 mg twice a day) as measured by improvement in scores in the five efficacy assessments. The observation that etodolac is as efficacious as three commonly used NSAIDs should interest clinicians who attempt to tailor NSAID therapy to the needs of individual RA patients, since etodolac has previously demonstrated an excellent safety profile. However, these trials must be completed to verify these preliminary results in a greater number of patients.

Double-blind controlled clinical trial of oral S-adenosylmethionine versus piroxicam in knee osteoarthritis

A double-blind, randomized, 84-day controlled clinical trial was carried out to compare orally administered S-adenosylmethionine (SAMe) (1,200 mg per day) with oral piroxicam therapy (20 mg per day) in the management of unilateral knee osteoarthritis. The ability of each drug to maintain the results achieved at the end of the treatment period was also evaluated during a 56-day follow-up period. Forty-five patients completed the study, 22 in the SAMe group and 23 in the piroxicam group. Both SAMe and piroxicam proved effective in inducing a significant improvement in the total pain score after 28 days of treatment. With regard to the other clinical parameters (i.e., morning stiffness, the distance walked before the onset of pain, active and passive motility), improvement started from about Day 56 in both groups. No significant difference was found between the two treatments in terms of efficacy and tolerability. Patients treated with SAMe maintained clinical improvement achieved at the end of treatment longer than did patients receiving piroxicam.

Alterations in neutrophil superoxide production following piroxicam therapy in patients with rheumatoid arthritis.

Twenty patients with classical rheumatoid arthritis were enrolled in a study to determine the effects of piroxicam therapy on neutrophil function as defined by chemotaxis and superoxide anion (O2-) production. T-lymphocyte chemotaxis was also evaluated in these patients. Leukocytes were obtained from these subjects initially, after two weeks of placebo treatment, and subsequently after four and 10 weeks of piroxicam therapy (20 mg, once daily). Responses were compared to simultaneously tested normal controls and to the patient's own cells obtained at the different time points. Studies showed that four and 10 weeks of piroxicam therapy resulted in significantly suppressed neutrophil O2- production in response to phorbol myristate acetate (PMA) and formyl methionyl leucyl phenylalanine (FMLP). O2- production in response to opsonized zymosan was not significantly affected after four weeks of therapy, but was significantly reduced after 10 weeks of therapy when compared to the patient's own cell response after two weeks of placebo treatment. Unlike O2- production, PMN random migration and chemotaxis in response to C5a or FMLP did not differ significantly from normal or untreated patient controls. Analysis of T-lymphocyte migration showed that T-cell random migration or migration to the chemokinetic agent, casein, was not significantly altered by piroxicam therapy. However, when T lymphocytes were tested for chemotaxis in response to lymphocyte-derived chemotactic factor for T cells (LCF), T cell migration was significantly suppressed after 10 weeks of therapy. Furthermore, when T cells from these subjects were cultured for 24 h, random migration was significantly reduced after four and 10 weeks of piroxicam therapy when compared to the patient prior to therapy, and migration in response to LCF was suppressed after four weeks of therapy when compared to normal controls. These data indicate that in patients with rheumatoid arthritis, treatment with piroxicam will significantly suppress PMN O2- production and may also alter the locomotor capacity of T lymphocytes. These actions may contribute to the antiinflammatory effects of piroxicam.