A double-blind evaluation of the analgesic efficacy and toxicity of oral ketorolac and diclofenac in cancer pain

Aim: To compare the analgesic efficacy and toxicity of the nonsteroidal ant i-inflammatory analgesic drug, ketorolac (Toradol(R), Recordati spa, Milan) 10 mg p.o. (t.i.d.) with diclofenac (Voltaren(R), Novartis Farma, Origgio, VA) 50 mg p.o. (t.i.d.) in cancer patients with moderate to severe chronic pain. Methods and study design: The Study was a multicenter randomized double bli nd cross-over trial. Each treatment lasted 7 days, after which the patients crossed over to the other drug. Pain intensity was evaluated by the visual analogue scale (VAS) after the first dose and by the B-point verbal rating scale (VRS) by the patient and by the physician following the 7;day treatm ent. Results and conclusions: A total of 138 advanced cancer patients were enrol led in the study. Overall 251 single-dose administration's (117 cross-over observations) and 257 multiple treatments (127 cross over experiments) were assessable. After a single administration of ketorolac and diclofenac, no significant difference could be observed in analgesic activity, as indicate d by the area under the pain-intensity time curve (AUC(0-5). a), in the max imum efficacy, or the duration of efficacy of the two drugs. The Westlake c onfidence intervals of the AUC(0-8) ratio (ketorolac : diclofenac) (1.07; 9 0% CI, 0.94-1.19), of the maximum efficacy ratio (1.03; 90% CI, 0.92-1.14), and the duration of efficacy ratio (1.05; 90% CI, 0.97-1.11) showed the bi oequivalence of the two drugs. Satisfactory pain relief was reported for mu ltiple 7-day treatments, with no significant differences between the two th erapies: according to the physician's evaluation, In 93/128 (73%; 95% CI, 6 5-80%) ketorolac treatments and 91/129 (71%; 95% CI, 63-78%) diclofenac tre atments: according to the patient's evaluation, in 83/128 cases (65%; 95% C I, 57-73%) after ketorolac and in 74/129 cases (57%; 95% CI, 49-66%) after diclofenac. Adverse symptoms were acceptable with both drugs. Interestingly , a pronounced sequence effect was found: gastric disturbances after ketoro lac were observed mainly (10 out of 15 observed events) when the drug was g iven to patients pretreated with diclofenac.