Beyond The Abstract - Non-Steroidal Anti-Inflammatory Drugs In The Treatment Of Genitourinary Malignancies: Focus On Clinical Data

Main Category: Urology / Nephrology
Also Included In: Cancer / Oncology;  Clinical Trials / Drug Trials
Article Date: 16 Dec 2007 - 0:00 PST

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UroToday.com - Non-steroidal anti-inflammatory drugs (NSAIDs) have been available for many years and exert their anti-inflammatory effects primarily through inhibition of the cyclooxygenase (COX) enzymes. Accumulating evidence from animal models, epidemiologic studies and clinical trials, suggests that NSAIDs, either selective or non-selective for cyclooxygenase isozymes, may be useful in prevention or treatment of a variety of tumours including colorectal, breast, lung, gastric, oesophageal, liver, urogenital and head and neck.

An electronic search of the literature to identify reports on the use of NSAIDs in the treatment of urological malignancies, in particular, was performed. MEDLINE was searched for manuscripts and the American Society of Clinical Oncology website for meeting abstracts.

As far as epidemiologic data investigating an association between NSAID use and prostate cancer incidence are concerned one meta- analysis of 12 studies, 7 prospective and 5 retrospective, and two more prospective studies were identified. All showed a modest reduction of prostate cancer detection in patients using NSAIDs supporting an anti-tumour effect but results were not statistically significant. COX-2 over expression in malignant prostate tissue was found in several trials but others have contradicted these results.

As far as clinical trials on prostate cancer are concerned, 3 full papers have been published regarding use of Cox-2 inhibitors in biochemical relapse after initial treatment with curative intent. All showed a decrease in PSA progression rate or even PSA normalization but the clinical significance of this in terms of survival is not known.

Two abstracts and one full paper have been published regarding use of Cox-II inhibitor monotherapy in advanced hormone- refractory cancer and four more abstracts have evaluated NSAID use in combination with other treatment modalities in the same setting. All studies have used PSA response as an outcome measure and results were encouraging. Again the survival benefit is not known.

As far as bladder cancer is concerned, over-expression of Cox-II has been identified in bladder tumors and two epidemiological studies, one population-based, case-control and one retrospective analysis of prescription claims, suggest a reduction in incidence and recurrence of bladder tumors with NSAID use respectively. Nevertheless no clinical trials have tested therapeutic effectiveness of anti-inflammatory drugs in bladder cancer.

Three full pares have been published on the use of Cox-II inhibitors in the advanced renal cancer setting in combination with other modalities. The addition of NSAIDs did not significantly affect response. This, in combination with the introduction of well-tolerated and efficacious targeted therapies for advanced renal cancer, has made NSAIDs unattractive for further evaluation and development in this indication.

Given the above, it is difficult to predict the future of anti-inflammatory drugs in the treatment of genitourinary tumours. The rationale of their use is supported by preclinical data. Unfortunately, clinical evidence is scarce or non-existent with the exception of prostate cancer. In this case preliminary but largely positive data are published justifying further evaluation. The optimum NSAID, its dose, possible combinations with other treatment modalities and the clinical setting for its administration should be established after assessment of the risk/benefit ratio in well designed prospective trials. Clinical trials in bladder cancer patients are also needed to validate positive preclinical evidence. Unfortunately, limited efficacy discourages NSAID use in treatment of renal cancer.

Written by

Giannitsas K, MD, Konstantinopoulos A,MD, Perimenis P, MD, as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

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