Injectable ketoprofen vs. acetylsalicylic acid for the relief of severe cancer pain: a double-blind, crossover trial. Nimesulide and diclofenac in the control of cancer-related pain. Comparison between oral and rectal administration. Naproxen sodium in treatment of bone pain due to metastatic cancer. [Clinical testing of a new analgesic combination on cancer patients in chronic pain]. Flurbiprofen for the treatment of bone pain in patients with metastatic breast cancer. Efficacy and tolerance of oral dipyrone versus oral morphine for cancer pain. Analgesic efficacy of ketoprofen in postpartum, general surgery, and chronic cancer pain. Aspirin and pancreatic cancer pain. Ketorolac, a new non-opioid analgesic: a double-blind trial versus pentazocine in cancer pain. A double-blind study comparing two single-dose regimens of ketorolac with diclofenac in pain due to cancer. Double-blind evaluation of short-term analgesic efficacy of orally administered diclofenac, diclofenac plus codeine, and diclofenac plus imipramine in chronic cancer pain. A double-blind evaluation of the analgesic efficacy and toxicity of oral ketorolac and diclofenac in cancer pain. The TD/10 recordati Protocol Study Group. Combination therapy with ibuprofen and methadone for chronic cancer pain. Medical therapy of malignant nerve pain. A randomised double-blind explanatory trial with naproxen versus slow-release morphine. Ketorolac versus diclofenac sodium in cancer pain. The dose-response relationship of controlled-release codeine (Codeine Contin) in chronic cancer pain. Comparison of morphine and ketorolac for intravenous patient-controlled analgesia in postoperative cancer patients. The efficacy of choline magnesium trisalicylate (CMT) in the management of metastatic bone pain: a pilot study. Naproxen versus aspirin as analgesics in advanced malignant disease. Morphine-sparing effect of diclofenac in cancer pain. Sodium naproxen versus sodium diclofenac in cancer pain control. Non-steroidal anti-inflammatory drugs as the first step in cancer pain therapy: double-blind, within-patient study comparing nine drugs. A double-blind parallel evaluation of the efficacy and safety of a single dose of ketoprofen in cancer pain. A comparison of two nonsteroidal antiinflammatory drugs (diflunisal versus dipyrone) in the treatment of moderate to severe cancer pain: a randomized crossover study. Ketorolac tromethamine in cancer pain. A double-blind study with placebo control of intramuscular ketorolac tromethamine in the treatment of cancer pain. A multiinstitutional evaluation of the analgesic efficacy and safety of ketorolac tromethamine, acetaminophen plus codeine, and placebo in cancer pain. [Drug therapy in severe tumor pain. Comparative study of a new combination preparation versus diclofenac-Na]. Nimesulide in the treatment of advanced cancer pain. Double-blind comparison with naproxen. Comparison of piroxicam and acetylsalicylic acid for pain in head and neck cancers: a double-blind study. Double-blind evaluation of analgesic efficacy of orally administered diclofenac, nefopam, and acetylsalicylic acid (ASA) plus codeine in chronic cancer pain. Analgesia with oral narcotics and added ibuprofen in cancer patients.
Thirty-six patients suffering from severe pain due to bone involvement from cancer participated in an analgesic study that compared single doses of ketoprofen 100 or 400 mg iv or injectable acetylsalicylic acid 1 g. A double-blind, balanced incomplete block design was adopted, in which each patient received two of the three test treatments, with an interval of 24 hours. Ketoprofen 400 mg proved significantly superior to 100 mg of the same drug, and was superior to 1 g of the acetylsalicylic acid derivative in the patients' assessment of the overall response. This was expressed by a visual analog scale and preferences. No adverse reaction was observed with any treatment. 64 patients with pain associated with advanced cancer were treated with either nimesulide or diclofenac as initial analgesia. Patients were randomly allocated to 1 of 4 treatment groups: oral nimesulide 300 mg/day; oral diclofenac 150 mg/day; rectal nimesulide 400 mg/day; and rectal diclofenac 200 mg/day. After 1 week of treatment, both drugs provided an adequate degree of pain relief and allowed an increase in sleep duration. There were no significant differences in efficacy between the drugs or routes of administration. Fewer side effects were observed with nimesulide, giving this agent a better therapeutic index than the reference compound. This multicenter, double-blind, randomized, parallel study compared the efficacy and safety of two dosages of naproxen sodium (NS) in 100 patients with bone pain due to metastatic cancer. Patients were asked to rate their pain on a scale of 0-99; those patients with pain scores of 40 or more (indicating moderate to severe pain) were enrolled. Patients receiving the high-dosage regimen (HDR; n = 51) received NS 550 mg every 8 h for 3 days. Those receiving the low-dosage regimen (LDR; n = 49) received on day 1 an initial dose of NS 550 mg followed by NS 275 mg capsules every 8 h through day 3. Patients evaluated pain intensity 8 times/day. During use of NS, pain intensity scores decreased by approximately one-third in each treatment group. Among patients who responded to NS, pain relief with the HDR was significantly greater than with the LDR. Differences between regimens in adverse events during treatment were non-significant; complaints were mainly gastrointestinal and mild. nan Two investigators enrolled 26 women with metastatic breast carcinoma in a six-week, double-blind, placebo-controlled, crossover study of flurbiprofen (Ansaid, Upjohn) and placebo. The study was designed to determine the efficacy of flurbiprofen in reducing bone pain due to metastatic breast cancer. Pain score, overall performance, and concomitant use of narcotics were evaluated. The overall mean differences in pain scores between flurbiprofen and placebo showed better control of pain during treatment with flurbiprofen. None of these differences approached statistical significance. Evaluation of overall performance status reached statistical significance in one investigator's group. Three out of four patients reported decreased consumption of acetaminophen/aspirin plus codeine combinations while receiving flurbiprofen. In a double-blind, randomised and parallel clinical trial, two oral doses of dipyrone (1 and 2 g) administered every 8 h were compared with 10 mg of oral morphine given every 4 h for the relief of chronic cancer pain. A total of 121 patients with cancer pain without gastric involvement participated in a 7-day treatment course and were allocated to receive either dipyrone 1 g (n = 41), dipyrone 2 g (n = 38) or morphine (n = 42). Drug efficacy was analysed according to the degree of pain relief using a 100-mm visual analogue scale, and the number of patients who decided to increase the dose of the analgesic drug on day 4. The analgesic effect of dipyrone, 2 g every 8 h, was similar to that of morphine. The efficacy of both schedules was significantly greater than that of dipyrone, 1 g every 8 h. Dipyrone at either 1 or 2 g doses tended to be better tolerated than morphine, although the differences were not statistically significant. This article summarizes the results of five single-dose clinical studies of three pain models: postpartum, postoperative, and chronic cancer pain. The efficacy of ketoprofen (in varying doses from 25 to 225 mg) was compared with one of the following standards: aspirin (650 mg), codeine (90 mg), acetaminophen (650 mg) plus codeine (60 mg), and parenteral morphine (5 mg and 10 mg). The results indicate that ketoprofen in doses as low as 25 mg has analgesic properties significantly superior to those of placebo. For the treatment of postpartum pain, ketoprofen was significantly more effective than aspirin 650 mg but not significantly different from codeine 90 mg. Ketoprofen doses of 50 mg and 150 mg also provided analgesia superior to that with acetaminophen 650 mg plus codeine 60 mg for the management of moderate to severe postoperative pain. Moreover, oral doses of ketoprofen (75 and 225 mg) provided analgesia similar to that obtained with 5 and 10 mg parenteral doses of morphine. Adverse effects related to ketoprofen were relatively minor and infrequent. Ketoprofen was recently approved for use as an analgesic for treatment of mild to moderate pain in total daily doses up to 300 mg; the recommended initial dose is 25 to 50 mg every 6 to 8 hours as necessary. nan A randomized double-blind trial was performed to evaluate the efficacy of a new non-steroidal anti-inflammatory analgesic drug, ketorolac, in the treatment of cancer pain compared with the opioid pentazocine. A total of 40 patients with moderate to severe cancer pain were studied, 20 patients being treated with 10 mg ketorolac given orally every 6 h and 20 receiving 50 mg pentazocine given orally every 6 h for up to 7 days. A reduction in the severity of the pain was recorded in both treatment groups with no significant difference in efficacy being found between the two therapies, although withdrawals due to adverse reactions were significantly less in the ketorolac-treated group (p less than 0.005). It is concluded that ketorolac may be a useful and more acceptable alternative to opioids in the treatment of cancer pain. To compare the analgesic efficacy and safety of two single doses of ketorolac with diclofenac in acute cancer pain.
                Double-blind, randomized, clinical study.
                Hospital-based clinical research center.
                One hundred eighty patients suffering acute, moderate, or severe cancer pain.
                A single intramuscular injection of ketorolac 10 or 30 mg or diclofenac 75 mg.
                Pain intensity was assessed 30 minutes and 1, 2, 3, 4, 5, and 6 hours after injection or until rescue drug administration. In approximately 70% of patients all treatments provided prompt sustained pain relief throughout the 6-hour observation period. There were no statistically significant differences in any of the analyzed efficacy measures among the three groups.
                Intramuscular ketorolac 10 mg is adequate to relieve cancer pain, and is equivalent to ketorolac 30 mg and to diclofenac 75 mg. A prospective double-blind randomized trial was conducted on 184 cancer patients with moderate to severe chronic pain to evaluate the analgesic efficacy and tolerability of diclofenac alone (50 mg q.i.d.) or in combination with a weak opioid (codeine 40 mg q.i.d.), or with an anti-depressant (imipramine, 10 or 25 mg t.i.d.). All demographic and clinical characteristics including cancer type, presence of bone metastases, baseline pain severity, neuropathic and nociceptive pain, and depressive state, were well balanced between the three treatment groups. The main analysis of the study was on the VAS scores at visit 2 (day 4). The mean VAS values for both associations imipramine plus diclofenac and codeine plus diclofenac were similar to the association placebo plus diclofenac. Patients on imipramine plus diclofenac and on placebo plus diclofenac were withdrawn mainly for inadequate efficacy, while patients on codeine plus diclofenac discontinued equally for inadequate efficacy or adverse events. In conclusion, in a short-term evaluation the addition of a tricyclic anti-depressant or a weak opioid to diclofenac did not provide further analgesia with respect to diclofenac administration alone. To compare the analgesic efficacy and toxicity of the nonsteroidal anti-inflammatory analgesic drug, ketorolac (Toradol, Recordati spa, Milan) 10 mg p.o. (t.i.d.) with diclofenac (Voltaren, Novartis Farma, Origglo, VA) 50 mg p.o. (t.i.d.) in cancer patients with moderate to severe chronic pain.
                The study was a multicenter randomized double-blind 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 5-point verbal rating scale (VRS) by the patient and by the physician following the 7-day treatment.
                A total of 138 advanced cancer patients were enrolled in the study. Overall 251 single-dose administrations (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 indicated by the area under the pain-intensity time curve (AUC0-8), in the maximum efficacy, or the duration of efficacy of the two drugs. The Westlake confidence intervals of the AUC0-8 ratio (ketorolac: diclofenac) (1.07; 90% 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 bioequivalence of the two drugs. Satisfactory pain relief was reported for multiple 7-day treatments, with no significant differences between the two therapies: according to the physician's evaluation, in 93/128 (73%; 95% CI, 65-80%) ketorolac treatments and 91/129 (71%; 95% CI, 63-78%) diclofenac treatments; according to the patient's evaluation, in 83/128 cases (65%; 95% CI, 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 ketorolac were observed mainly (10 out of 15 observed events) when the drug was given to patients pretreated with diclofenac. This randomized double-blind crossover study compares the narcotic methadone alone with methadone in combination with the peripherally acting, antiprostaglandin agent ibuprofen (Motrin, Upjohn) in 28 patients with moderate to severe cancer-related pain, who were already using a narcotic for pain relief. Results show that the addition of 600 mg of ibuprofen to either 2.5 or 5 mg of methadone significantly increased analgesia, without concomitantly increasing side effects or euphoria. It is uncertain whether there exists a nociceptive component in malignant nerve pain responsive to NSAIDs and opioids. 20 patients with malignant nerve pain were randomly assigned to treatment with naproxen 1500 mg versus slow-release morphine 60 mg daily during 1 week, followed by cross-over medication during the second week in a double-blind, double-dummy protocol. In the 16 evaluable patients, a significant (P < 0.05) reduction of 26% (S.E. +/- 7.9) in pain intensity was reached at day 7, compared to baseline pain. At day 7, significant pain relief of 32% (P < 0.05) was observed in the naproxen group, but not in the morphine group (21%, P = 0.14). Patients using morphine needed approximately twice as much paracetamol rescue than patients using naproxen. Additional pain relief could be observed in 4/9 patients with cross-over medication. These data support the concept of a nociceptive component in malignant nerve pain responding to NSAIDs and opioids, and favour the combination of both an anti-inflammatory drug and an opioid for symptomatic pain relief. In a randomized single-blind study carried out simultaneously in five Departments for Pain Therapy and Palliative Care, the analgesic efficacy and side effects of oral ketorolac (ketorolac tromethamine, Tora-Dol, CAS 74103-07-4) and diclofenac sodium were compared in a population of 100 advanced cancer patients suffering from somatic and/or visceral pain. The treatment was carried out in agreement with the first step of the WHO pharmacological strategy in cancer pain. The administered dosage was 10 mg every 6 h for ketorolac and 50 mg every 8 h for diclofenac sodium. The study showed the efficacy of both drugs in cancer pain. A greater number of keterolac patients could pass to the second WHO step later than diclofenac patients. As to the tolerability, both drugs turned out to be similar, except for "sleepiness", which was four times more frequent (p < 0.05) in the diclofenac group. The improved pain control provided by regular dosing of opioid analgesics in patients with severe cancer pain has been well established. However, the treatment of mild-to-moderate cancer pain is often limited to "as needed" dosing with fixed combinations of codeine or oxycodone plus a nonopioid analgesic, which do not allow optimal titration of the individual components. This randomized double-blind study was designed to evaluate the efficacy of controlled-release codeine (Codeine Contin) in patients with cancer pain, and to estimate its dose equivalence to a standard combination of acetaminophen plus codeine. Twenty-four patients with at least moderate cancer pain were randomized to Codeine Contin 100, 200, or 300 mg every 12 hr or acetaminophen plus codeine (600 mg/60 mg) every 6 hr. On days 1 and 4 of dosing, pain intensity and pain relief were assessed hourly for 12 hr. The sum of pain intensity differences (SPID) from baseline and the total pain relief (TOTPAR) scores demonstrated a dose-response relationship for Codeine Contin on days 1 and 4 that was statistically significant on day 1 and suggested greater analgesic efficacy on day 4, compared with day 1. Codeine Contin 150 mg every 12 hr was estimated to be equianalgesic to acetaminophen plus codeine (600 mg/60 mg) given every 6 hr. Because a similar equivalence was also demonstrated from analysis of adverse event data, it is concluded that Codeine Contin 150 mg produces analgesia and a side-effect profile similar to a 40% lower dose of codeine provided by the combination.(ABSTRACT TRUNCATED AT 250 WORDS) To compare the effectiveness of intravenous patient-controlled (i.v.-PCA) ketorolac to i.v.-PCA morphine in the treatment of postoperative pain in cancer patients.
                In a double-blind, prospective, randomized trial, patients received either morphine in 1 mg/ml concentration or ketorolac 5 mg/ml for postoperative pain control. On arrival to the postanesthesia care unit (PACU), the patients received 2 ml of medication every 5 min, until satisfactory analgesia was achieved. If pain persisted after 20 ml of study drug had been administered, 0.1 mg/kg morphine was given i.m. On discharge from the PACU, the patients were placed on an i.v.-PCA pump. All patients received a basal infusion of 1 ml/h with a 1-ml on-demand bolus and a lockout interval of 10 min. Patients were offered 0.1 mg/kg morphine IM every 6 h, which they could refuse.
                University Cancer Center.
                Seventy patients scheduled for abdominal or truncal cancer operations.
                Visual analog pain scores (VAPS) and Visual analog sedation scores (VASS) were used to measure the quality of pain control achieved either with ketorolac or morphine. The incidence of side effects was documented.
                The VAPS were comparable between the groups. Patients in the ketorolac group requested more supplemental i.m. morphine. However, the total morphine dose and incidence of side effects was significantly higher in patients receiving i.v.-PCA morphine.
                These results indicate that ketorolac supplemented with small doses of morphine is associated with a lower incidence of nausea, vomiting, and pruritus compared to morphine alone. This combination should be considered where immunosuppression from operation and administration of morphine is undesirable. Twenty-six patients with painful, bony metastases were recruited into a randomized, double-blind, single dose, two-treatment, three-part crossover study of choline magnesium trisalicylate (CMT) and placebo. Assessments were made prior to and at one, two, three and four hours after dosing. Bone pain caused by metastatic cancer was significantly relieved one hour after the administration of 1500 mg CMT (p = 0.04). At all four time points the pain was less than baseline with CMT and at three time points greater than baseline with placebo but these results did not reach statistical significance. The summed pain intensity difference for patients was greater with CMT than with placebo, but this also did not reach significance. The incidence of volunteered side-effects was similar for both treatments. The results suggest that a nonacetylating, nonsteroidal anti-inflammatory drug may have a role complementary to that of an opioid in the management of metastatic bone pain. nan The effectiveness of diclofenac 50 mg t.i.d. as additive treatment to parenteral patient-controlled administration therapy (PCAT) with morphine in cancer pain has been investigated in a double-blind study. In the fifteen patients who completed the study, morphine i.v. was titrated to optimal pain relief over 5 days. The mean total morphine consumption was significantly reduced during diclofenac administration (82.8 mg morphine per day) compared to placebo (95.0 mg morphine per day). The reduction in mean morphine consumption during active treatment with diclofenac was independent of the initial dose of self-titrated morphine. Pain, self-assessed according to VAS, tended to be lower during the diclofenac period, although the difference did not reach statistical significance. No adverse events were recorded among the 15 patients who completed the study. The present findings show that a non-steroidal anti-inflammatory agent, such as diclofenac, has a morphine-sparing effect in morphine-treated patients with cancer pain. In a single-blind random study, simultaneously carried out by five Pain Therapy and Palliative Care Centres, the analgesic power and side-effects of sodium naproxen (CAS 26159-34-2) and sodium diclofenac (CAS 15307-86-5) by mouth were compared in a group of 100 advanced cancer patients. The patients complained of somatic and/or visceral pain and were treated with non-steroid anti-inflammatories as required. The dose administered amounted to 550 mg every 12 h for sodium naproxen and to 100 mg every 12 h for sodium diclofenac. The study stressed the similar analgesic effect of the two drugs--pain intensity and duration decreased by half in the first week of treatment--and a comparatively low morbidity rate. The efficacy and tolerability of acetylsalicylic acid, paracetamol, diclofenac, ibuprofen, indomethacin, pirprofen, sulindac, naproxen and suprofen were compared in the treatment of cancer pain. In a double-blind, within-patient randomized study, each drug was given for 1 week to eight patients and for another week to a further eight patients. A total of 65 patients were effectively treated; only 48 completed week 1 and 41 completed week 2. Naproxen, diclofenac and indomethacin were highly effective in pain relief (tested by means of a 100 mm visual analogue scale) and were relatively well tolerated. It is concluded that these non-steroidal anti-inflammatory drugs can be considered as first choice in the treatment of cancer pain. The analgesic effects of single oral doses of ketoprofen 100 and 300 mg, the combination of aspirin 650 mg plus codeine 60 mg, and placebo were compared under double-blind conditions in 160 hospitalized patients with cancer pain. At baseline and at 30 minutes and hourly for 6 hours after treatment, patients evaluated their pain intensity and pain relief. The 100 mg ketoprofen dose was significantly (P less than 0.05) superior to placebo for all 14 derived efficacy parameters; the 300 mg dose was significantly superior to placebo in all assessments except derived onset of relief. Aspirin plus codeine was significantly (P less than 0.05) superior to placebo for nine of the 14 assessments. No statistically significant differences were observed among active treatments for any of the 14 derived parameters. The number of patients with a "good" response was greatest in the ketoprofen 100 mg group (55%); the numbers of good responders in the aspirin plus codeine (37.5%) and the ketoprofen 300 mg (30%) groups were comparable. The three active treatment groups were not significantly different from each other for patient response. The numbers of patients requiring rescue analgesic were significantly (P less than 0.05) lower for both ketoprofen groups, but not for the aspirin plus codeine group, as compared with the placebo group. Twenty-three percent of the 160 patients reported adverse experiences, but there were no significant differences between the treatment groups in the number or type of experience. These results show that ketoprofen is as effective and well tolerated as aspirin plus codeine in relieving cancer pain. The efficacy of diflunisal in cancer pain was evaluated and compared with dipyrone. Diflunisal was given at the dosage of 500 mg perorally twice a day, and dipyrone was given at the dosage of 500 mg perorally three times a day. Duration of each treatment was 7 days; after a 12-hour wash-out period, patients were given the other drug for another 7 days. A total of 50 patients were enrolled in the study. Pain intensity was assessed by 10-point visual analog scale (VAS). Patients who had a VAS score higher than 5 were included. A total of 47 patients were evaluable. Initial VAS score was a mean of 8.57+/-1.33. Diflunisal reduced the pain score by a mean of 4.65+/-3.10, whereas dipyrone reduced the pain score by a mean of 3.25 < or = 2.85 (p < 0.001). Patients were also analyzed in three subgroups according to the presence of nonmetastatic, metastatic, and bone metastatic diseases. In each of these subgroups, diflunisal reduced the pain score more than dipyrone; however, the difference was statistically significant only in patients who had bone metastasis. Adverse reactions were rare and acceptable with both drugs. Diflusinal is superior to dipyrone at this dosage and schedule in the treatment of moderate to severe cancer pain. nan The analgesic efficacy of ketorolac tromethamine was compared to placebo in 126 patients suffering moderate or severe chronic pain due to cancer in a double-blind parallel randomized study. Ketorolac was administered intramuscularly in doses of 10, 30 or 90 mg. Pain intensity and pain relief were assessed for 6 hours by scoring standard verbal scales and an overall assessment of the medication was given by the patients and the observer on completion of the study. Each dose of ketorolac was statistically superior to placebo for the sum of pain intensity difference (SPID) but no difference was seen between the three ketorolac regimens. When the ketorolac groups are combined, there was a significantly better pain relief as compared to placebo. The global evaluation scores were also statistically superior in the ketorolac groups combined than in the placebo group. A total of 15 patients reported minor adverse events, 10 being after ketorolac doses. This study shows that single intramuscular doses of ketorolac of 10 mg and above are effective in the relief of cancer pain, and are associated with a low incidence of side-effects. Seventy-five patients with moderate to severe cancer pain were randomly assigned in a double-blind fashion to receive first-dose ketorolac tromethamine 10 mg orally, acetaminophen 600 mg plus codeine 60 mg orally, or placebo, followed by subsequent doses of ketorolac or acetaminophen plus codeine four times daily for 7 days. Patient characteristics were similar among the treatment groups. The first-dose observation documented that both ketorolac and acetaminophen plus codeine produced an equivalent reduction in cancer pain and were superior to placebo as measured by pain intensity differences and pain relief. Multidose comparison documented a small but statistically significant advantage in mean daily pain relief favoring acetaminophen plus codeine, although there were no differences in mean daily ratings of overall effects for either study medication. Adverse symptoms were acceptable with both ketorolac and acetaminophen plus codeine. We conclude that ketorolac has significant analgesic activity in patients with cancer pain, although its precise role in the treatment regimen of these patients remains undefined. In a multicentric, interindividual, double-blind study, the analgesic action, duration of effect, tolerability and side effects of the new combination preparation, Combaren (diclofenac-Na 50 mg+codeine phosphate 50 mg), were compared with those of diclofenac-Na 50 mg (Voltaren 50) in 184 patients with severe tumor-related pain. The results show that Combaren is a highly effective preparation for the treatment of severe tumor pain. The combination of diclofenac-Na with codeine phosphate leads to a clear, statistically significant, augmentation of the effectiveness of additionally used analgesics on pain severity, and the general effectiveness of the combination is more positively assessed that that of monotherapy with diclofenac (also effective). In the staged approach to the treatment of malignancy-related pain in which the aim is to provide continuous, preventive analgesia rather than ad hoc treatment of newly developing or worsening pain, this combination preparation will presumably find a permanent place in stage I/II of the generally accepted staged pain-treatment scheme. In a clinical double-blind study, the analgesic efficacy and the side-effects of nimesulide (Aulin, CAS 51803-78-2) and naproxen administered to 68 patients affected by advanced cancer pain were compared. Patients were treated with non-steroidal anti-inflammatory drugs according to the first step of the pharmacological analgesic scale of the WHO. The dose administered was 200 mg b.i.d. (every 12 h) for nimesulide and 500 mg b.i.d. (every 12 h) for naproxen. From this study the analgesic effect and the tolerability of the two drugs appeared to be similar. Both drugs resulted to be effective with a low incidence of adverse events that may be related to their use. This double-blind, placebo controlled study compared the analgesic efficacy of piroxicam with acetylsalicylic acid (ASA) in patients having continuous pain with advanced head and neck cancers. They were randomly divided into two groups of 25 patients each; 36 of these 50 patients completed the study. After four days of treatment, there was a significant reduction in a modified numerical rating scale (NRS) of pain in the piroxicam group as well as in the ASA group. There was a concomitant increase in the hours of sleep in the piroxicam group and in the ASA group. The decrease in NRS and the increase in sleeping hours was not statistically significantly different between the two groups. Patients receiving piroxicam had a low incidence of upper gastrointestinal side-effects compared with those receiving ASA. The results of this study suggest that piroxicam can be used as first line treatment in place of ASA in patients with head and neck cancers suffering from moderate to severe pain. The advantages are less frequent dosing, better patient compliance and few side-effects. The analgesic efficacy and toxicity of oral diclofenac sodium 50 mg (q.i.d.) vs. nefopam 60 mg (q.i.d.) and a combination of 640 mg ASA and 40 mg codeine (q.i.d.) in cancer patients with moderate to severe chronic pain has been evaluated in a randomized double-blind study. Planned duration of treatment was 10 days. Pain intensity was evaluated by a visual analog scale. The length of patient participation in the trial, the patient's final global evaluation and the incidence of side effects were also evaluated. Ninety-nine patients were enrolled in the study. All treatments produced a statistically significant pain relief (P less than 0.01) without differences among groups but only 26 of 99 patients (26.3%) completed the planned treatment period. Mean time in the study was 4.65 days. Inefficacy and side effects were the main reasons for premature treatment interruption. Patients treated with nefopam had a significantly shorter period in the study than patients treated with the other 2 treatments. Adverse effects were slightly more frequent with the nefopam and ASA + codeine regimens. The 3 therapeutic regimens appear to be similar as to analgesic efficacy, but diclofenac presents the advantage of a slightly better safety profile than nefopam and the ASA + codeine combination. A scheduled regimen of oral narcotic analgesics was compared with a regimen of oral narcotic analgesics plus ibuprofen for analgesic efficacy in patients with cancer. Ten patients with metastatic cancer were randomly assigned to receive either ibuprofen 400 mg or a look-alike placebo four times daily in addition to each patient's existing regimen of scheduled oral narcotics. A two-period changeover study design was used. The 24-hour narcotic intake equated to injectable morphine was computed for each patient at baseline and during the nine study days. A visual analogue scale was used to evaluate pain relief, nausea, mood depression, daytime drowsiness and nighttime sleeplessness. The analgesic efficacy of the narcotic-ibuprofen combination was significantly greater than the analgesic efficacy of the narcotic-placebo combination. Eight patients demonstrated a positive treatment effect with added ibuprofen; the overall improvement in analgesia averaged 39.1% in these patients. There was no significant increase from baseline in the incidence of nausea, mood depression, daytime drowsiness or nighttime sleeplessness. At the doses used in this study, a treatment regimen of oral narcotic analgesics plus ibuprofen was more effective than oral narcotics alone in relieving pain associated with cancer.
Based upon limited data, NSAIDs appear to be more effective than placebo for cancer pain; clear evidence to support superior safety or efficacy of one NSAID over another is lacking; and trials of combinations of an NSAID with an opioid have disclosed either no difference (4 out of 14 papers), a statistically insignificant trend towards superiority (1 out of 14 papers), or at most a slight but statistically significant advantage (9 out of 14 papers), compared with either single entity. The short duration of studies undermines generalization of their findings on efficacy and safety of NSAIDs for cancer pain.