Use of Non-Steroidal Anti-Inflammatory Drugs and Prostate Cancer Risk: A Population-Based Nested Case-Control Study

BACKGROUND: Despite strong laboratory evidence that non-steroidal anti-inflammatory drugs (NSAIDs) could prevent prostate cancer, epidemiological studies have so far reported conflicting results. Most studies were limited by lack of information on dosage and duration of use of the different classes of NSAIDs. METHODS: We conducted a nested case-control study using data from Saskatchewan Prescription Drug Plan (SPDP) and Cancer Registry to examine the effects of dose and duration of use of five classes of NSAIDs on prostate cancer risk. Cases (N = 9,007) were men aged ≥40 years diagnosed with prostatic carcinoma between 1985 and 2000, and were matched to four controls on age and duration of SPDP membership. Detailed histories of exposure to prescription NSAIDs and other drugs were obtained from the SPDP. RESULTS: Any use of propionates (e.g., ibuprofen, naproxen) was associated with a modest reduction in prostate cancer risk (Odds ratio = 0.90; 95%CI 0.84-0.95), whereas use of other NSAIDs was not. In particular, we did not observe the hypothesized inverse association with aspirin use (1.01; 0.95-1.07). There was no clear evidence of dose-response or duration-response relationships for any of the examined NSAID classes. CONCLUSIONS: Our findings suggest modest benefits of at least some NSAIDs in reducing prostate cancer risk

Impact of the frequency of online verifications on the patient set-up accuracy and set-up margins

<p>Abstract</p> <p>Purpose</p> <p>The purpose of the study was to evaluate the patient set-up error of different anatomical sites, to estimate the effect of different frequencies of online verifications on the patient set-up accuracy, and to calculate margins to accommodate for the patient set-up error (ICRU set-up margin, SM).</p> <p>Methods and materials</p> <p>Alignment data of 148 patients treated with inversed planned intensity modulated radiotherapy (IMRT) or three-dimensional conformal radiotherapy (3D-CRT) of the head and neck (n = 31), chest (n = 72), abdomen (n = 15), and pelvis (n = 30) were evaluated. The patient set-up accuracy was assessed using orthogonal megavoltage electronic portal images of 2328 fractions of 173 planning target volumes (PTV). In 25 patients, two PTVs were analyzed where the PTVs were located in different anatomical sites and treated in two different radiotherapy courses. The patient set-up error and the corresponding SM were retrospectively determined assuming no online verification, online verification once a week and online verification every other day.</p> <p>Results</p> <p>The SM could be effectively reduced with increasing frequency of online verifications. However, a significant frequency of relevant set-up errors remained even after online verification every other day. For example, residual set-up errors larger than 5 mm were observed on average in 18% to 27% of all fractions of patients treated in the chest, abdomen and pelvis, and in 10% of fractions of patients treated in the head and neck after online verification every other day.</p> <p>Conclusion</p> <p>In patients where high set-up accuracy is desired, daily online verification is highly recommended.</p

Potentiation of anti-cancer drug activity at low intratumoral pH induced by the mitochondrial inhibitor m-iodobenzylguanidine (MIBG) and its analogue benzylguanidine (BG)

Tumour-selective acidification is of potential interest for enhanced therapeutic gain of pH sensitive drugs. In this study, we investigated the feasibility of a tumour-selective reduction of the extracellular and intracellular pH and their effect on the tumour response of selected anti-cancer drugs. In an in vitro L1210 leukaemic cell model, we confirmed enhanced cytotoxicity of chlorambucil at low extracellular pH conditions. In contrast, the alkylating drugs melphalan and cisplatin, and bioreductive agents mitomycin C and its derivative EO9, required low intracellular pH conditions for enhanced activation. Furthermore, a strong and pH-independent synergism was observed between the pH-equilibrating drug nigericin and melphalan, of which the mechanism is unclear. In radiation-induced fibrosarcoma (RIF-1) tumour-bearing mice, the extracellular pH was reduced by the mitochondrial inhibitor m-iodobenzylguanidine (MIBG) or its analogue benzylguanidine (BG) plus glucose. To simultaneously reduce the intracellular pH, MIBG plus glucose were combined with the ionophore nigericin or the Na+/H+ exchanger inhibitor amiloride and the Na+-dependent HCO3−/Cl−exchanger inhibitor 4,4′-diisothiocyanostilbene-2,2′-disulphonic acid (DIDS). Biochemical studies confirmed an effective reduction of the extracellular pH to approximately 6.2, and anti-tumour responses to the interventions indicated a simultaneous reduction of the intracellular pH below 6.6 for at least 3 h. Combined reduction of extra- and intracellular tumour pH with melphalan increased the tumour regrowth time to 200% of the pretreatment volume from 5.7 ± 0.6 days for melphalan alone to 8.1 ± 0.7 days with pH manipulation (P< 0.05). Mitomycin C related tumour growth delay was enhanced by the combined interventions from 3.8 ± 0.5 to 5.2 ± 0.5 days (P< 0.05), but only in tumours of relatively large sizes. The interventions were non-toxic alone or in combination with the anti-cancer drugs and did not affect melphalan biodistribution. In conclusion, we have developed non-toxic interventions for sustained and selective reduction of extra- and intracellular tumour pH which potentiated the tumour responses to selected anti-cancer drugs. 1999 Cancer Research Campaig