A phase II study of ondansetron as antiemetic prophylaxis in patients receiving high-dose polychemotherapy and stem cell transplantation

The field of high-dose chemotherapy with stem cell transplantation has been expanded recently as a treatment for solid tumors and hematological malignancies. Severe emesis remains one of the main extramedullary side-effects of high-dose regimens during the first week of treatment. Traditional antiemetics such as chlorpromazine, diazepam, and phenothiazines are extensively used but are unable to control emesis. The new antiemetic ondansetron, a serotonin receptor (5HT₃) antagonist appears to be superior to these drugs for cisplatin-induced emesis. The study we present here is an attempt to control emesis following high-dose regimens, during bone marrow or peripheral stem cell transplantation, with ondansetron. To our knowledge no other paper has reported the efficacy of this antiemetic in such group of patients. A total of 29 patients who received highly emetogenic polychemotherapy as conditioning regimens for bone marrow transplantation were treated with ondansetron, which was given as an 8-mg i.v. short infusion prior the initiation of treatment and every 6 h thereafter for 3 days, and an 8-mg dose every 8 h for 5 additional days. All the patients had previously been treated with chemotherapy and were evaluable for response and toxicity. Complete and major protection of vomiting on day 1 was achieved by 76% of the patients, 58% on day 2 and 52% on day 3. Nausea was absent or mild in 79% of patients on day 1, 45% on day 2 and 41% on day 3. For the days 4–8 as a whole, complete and major protection against vomiting was achieved by 59%–86% of the patients, while 51%–90% of patients had no or mild nausea. The most frequent side-effects were headache (24%) and constipation (17%). On the basis of these results we conclude that ondasetron can be succesfully used as an effective antiemetic prophylaxis for patients who receive megatherapy and bone marrow rescue, and should allow the majority of these patients to receive their treatment without serious side-effects and discomfort.     

The antiemetic activity of high-dose alizapride and high-dose metoclopramide in patients receiving cancer chemotherapy: a prospective, randomized, double-blind trial

Alizapride is a new substituted benzamide with suggested superior antiemetic efficacy to and fewer side effects than metoclopramide. High-dose alizapride (4 mg/kg X five doses) was compared with high-dose metoclopramide (2 mg/kg X five doses) in a prospective, randomized, double-blind trial in 62 evaluable patients undergoing strongly emetic cancer chemotherapy. Patients receiving metoclopramide experienced significantly fewer vomiting episodes than patients receiving alizapride (median of three episodes vs. eight episodes; P less than 0.001). Metoclopramide was more effective in decreasing the volume of emesis than was alizapride (median of 100 ml vs. 360 ml; P less than 0.02). Seventy-two percent of the patients receiving alizapride and 57% of those receiving metoclopramide experienced side effects. High-dose metoclopramide is an effective antiemetic in patients receiving cancer chemotherapy. Alizapride is less effective and has more side effects than metoclopramide. We do not recommend the further use of alizapride.     

A dose-finding study of granisetron,a novel antiemetic,in patients receiving high-dose cisplatin

In this double-blind study, the efficacy and safety of a single intravenous dose of a novel antiemetic, granisetron, was assessed at two dose levels (40 g/kg and 160 g/kg). A group of 355 patients were given prophylactic granisetron prior to receiving highdose cisplatin chemotherapy. In the first 24 h, 57% and 59% of patients, respectively, experienced no vomiting and no more than mild nausea. Two further doses of granisetron (40 g/kg) were permitted in the first 24 h to treat any emergent symptoms of nausea and vomiting; 66 patients (39%) in the 40-g/kg treatment group and 56 patients (34%) in the 160-g/kg group received at least one additional dose. Additional treatment with granisetron resulted in resolution or improvement of symptoms in at least 73% of these patients. Over the 7-day study period, 52% of patients in the lower-dose group and 48% in the higher required no further conventional antiemetic therapy. The two different dose levels were equal both in terms in efficacy and safety. Granisetron was well tolerated throughout the dose range of the study [40–240 g kg^-1 (24 h)^-1]. The commonest adverse event was headache, seen in 14%–16% of patients. In all but one case this resolved spontaneously or responded to simple treatment.on behalf of the Granisetron Study Group     

Evaluation of ethanol as an antiemetic in patients receiving cisplatin

Nausea and vomiting are common complications of cisplatin chemotherapy. Patients with a history of chronic, heavy alcohol intake experience less nausea and vomiting from cisplatin than do those who are not heavy drinkers. Four patients being treated with cisplatin who had not obtained satisfactory control of nausea and vomiting with high-dose metoclopramide were given intravenous ethanol to alleviate their symptoms. In each case, the control of nausea and vomiting was inferior to that previously achieved with metoclopramide. It is concluded that acute ethanol administration has no clinically significant antiemetic effect in patients receiving cisplatin.     

A randomized, placebo-controlled trial of ondansetron, metoclopramide, and promethazine in adults

Objectives

The objective of the study was to assess whether ondansetron has superior nausea reduction compared with metoclopramide, promethazine, or saline placebo in emergency department (ED) adults.

Methods

This randomized, placebo-controlled, double-blinded superiority trial was intended to enroll a convenience sample of 600 patients. Nausea was evaluated on a 100-mm visual analog scale (VAS) at baseline and 30 minutes after treatment. Patients with a minimum preenrollment VAS of 40 mm were randomized to intravenous ondansetron 4 mg, metoclopramide 10 mg, promethazine 12.5 mg, or saline placebo. A 12-mm VAS improvement in nausea severity was deemed clinically important. We measured potential drug adverse effects at baseline and 30 minutes. Patients received approximately 500 mL of saline hydration during the initial 30 minutes.

Results

Of 180 subjects who consented, 163 completed the study. The median age was 32 years (interquartile range, 23-47), and 68% were female. The median 30-minute VAS reductions (95% confidence intervals) and saline volume given for ondansetron, metoclopramide, promethazine, and saline were −22 (−32 to −15), −30 (−38 to −25.5), −29 (−40 to −21), and −16 (−25 to −3), and 500, 500, 500, and 450, respectively. The median 30-minute VAS differences (95% confidence intervals) between ondansetron and metoclopramide, promethazine, and saline were −8 (−18.5 to 3), −7 (−21 to −5.5), and 6 (−7 to 20), respectively. We compared the antiemetic efficacy across all treatments with the Kruskal-Wallis test (P = .16).

Conclusions

Our study shows no evidence that ondansetron is superior to metoclopramide and promethazine in reducing nausea in ED adults. Early study termination may have limited detection of ondansetron's superior nausea reduction over saline.     

Ondansetron plus dexamethasone versus metoclopramide plus dexamethasone plus diphenhydramine in cisplatin-treated patients with ovarian cancer

Female patients with ovarian cancer are at high risk for emesis. A study evaluating the antiemetic activity and tolerability of ondansetron plus dexamethasone compared to metoclopramide plus dexamethasone plus diphenhydramine in this group of patients has been performed. A group of 63 patients with ovarian cancer undergoing cisplatin treatment were enrolled in the study. Vomiting, nausea and other side-effects were evaluated by the investigators during the first 24 h and recorded by the patients on a diary card on days 2–4. Ondansetron plus dexamethasone showed a higher antiemetic activity during the first 24 h after cisplatin administration in all three cycles of cisplatin treatment, giving over 90% complete protection from vomiting at the first cycle. The efficacy of ondansetron plus dexamethasone decreased at the second cycle, but the percentage of complete protection from vomiting always remained better than 70%; there was poorer protection in the metoclopramide group, and its effect was similar during all three cycles. Ondansetron plus dexamethasone was also found to be more efficacious than the metoclopramide regimen on the second day after cisplatin administration, while on days 3–4 a high rate of complete protection from emesis was achieved by both antiemetic therapies (>80%). About 40%–55% of patients receiving ondansetron plus dexamethasone and about 65%–85% of patients treated with metoclopramide plus dexamethasone plus diphenhydramine reported nausea or vomiting during days 1–4. Ondansetron plus dexamethasone is more efficacious than metoclopramide plus dexamethasone plus diphenhydramine but new strategies to improve antiemetic efficacy in ovarian cancer patients must be outlined.     

Randomized,double-blind trial comparing the antiemetic effect of tropisetron plus metopimazine with tropisetron plus placebo in patients receiving multiple cycles of multiple-day cisplatin-based chemotherapy

Purpose To compare the antiemetic efficacy and tolerability of tropisetron plus metopimazine with tropisetron plus placebo during 4 cycles of multiple-day, cisplatin-based chemotherapy. Materials and methods 82 chemotherapy-naive patients with germ cell cancer scheduled to 4 cycles of multiple-day cisplatin-based chemotherapy (20 or 40 mg/m²/day for 5 days) given every 3 weeks were included. A double-blind parallel trial design was used and patients randomized to tropisetron plus metopimazine or tropisetron plus placebo. Tropisetron was administered as a single 5 mg intravenous dose on days 1–5 and a single 5 mg oral dose on day 6, and metopimazine as 30 mg orally t.i.d. on day 1, and q.i.d on days 2–6. Results Patients were evaluable for efficacy during a total of 195 cycles. Small, but certain advantages were obtained with the combination. In cycle 1, complete protection from emetic episodes on day 1, days 1–5, days 6–9 and days 1–9 was achieved in 85.7%, 42.9%, 86.2% and 40.5% with tropisetron plus metopimazine and in 90.0%, 22.5%, 64.3% and 17.5% with tropisetron plus placebo, respectively. This difference achieved statistical significance in the overall period, days 1–9 (P = 0.029). During the entire period (days 1–9), significantly less nausea was seen in patients receiving tropisetron plus metopimazine (P = 0.027), whereas other nausea parameters did not reach statistical significance. The cumulative emetic protection rate after 4 cycles was 0.51 with tropisetron plus metopimazine and 0.25 with tropisetron plus placebo (P = 0.037). Side effects were generally few and mild with both treatments and no significant differences were seen. Conclusion Tropisetron plus metopimazine is superior to tropisetron during 4 cycles of multiple-day cisplatin-based chemotherapy, but both treatments are ineffective in a number of patients. The effect of the combination seems comparable to that of ondansetron plus dexamethasone. Newer drugs such as the neurokinin₁ receptor antagonist, aprepitant, should be investigated to optimize antiemetic therapy in patients receiving multiple-day chemotherapy.     

Combination of aprepitant, palonosetron and dexamethasone as antiemetic prophylaxis in lung cancer patients receiving multiple cycles of cisplatin-based chemotherapy

Introduction: With repeated courses of chemotherapy, chemotherapy‐induced nausea and vomiting (CINV) becomes progressively more difficult to control. The aim of this study was to evaluate whether the antiemetic efficacy of the triple combination aprepitant, palonosetron and dexamethasone could be sustained for up to six cycles of highly emetogenic chemotherapy (HEC) (cisplatin ≥ 50 mg/m²). Methods: Chemotherapy‐naive patients receiving cisplatin‐based HEC, were treated with palonosetron 0.25 mg/i.v., dexamethasone 20 mg/i.v. and aprepitant 125 mg/p.o. 1 h before chemotherapy. Aprepitant 80 mg/p.o. and dexamethasone 4 mg/p.o. were administered on days 2–3. The primary endpoint was complete response (CR, no vomiting and no use of rescue medication), over 5 days following HEC in up to six cycles. Secondary endpoints were emesis‐free and nausea‐free rates. Safety was also evaluated. Results: One hundred and fifty six lung cancer patients were included in the study; the median age was 64 years and 76.9% were men. The minimum cisplatin dosage was 75 mg/m², and in most patients was combined with another drug (87.4%). CR ranged from 74.4% (first cycle) to 82% (sixth cycle). More than 90% and 60% of patients were emesis‐free and nausea‐free during all chemotherapy cycles. The most commonly reported side effects were constipation and headache. Conclusions: The triple combination of aprepitant, palonosetron and dexamethasone enhanced not only the antiemetic protection during the first cycle, but its efficacy was also sustained for up to six cycles of cisplatin‐based HEC in lung cancer patients.     

Randomized, double-blind comparison of granisetron versus granisetron plus prednisolone as antiemetic prophylaxis during multiple-day cisplatin-based chemotherapy

 Ninety chemotherapy-naive cancer patients receiving cisplatin-based (≥50 mg/m²) chemotherapy participated in a randomized, double-blind, cross-over study comparing the safety and efficacy of granisetron (GRA) versus granisetron plus prednisolone (GRA+PRE). All patients received i.v. granisetron 3 mg and were randomly allocated to oral prednisolone 50 mg or placebo prior to chemotherapy. At the subsequent cycle of chemotherapy, patients were crossed over to the other antiemetic treatment. A complete response, defined as no eme- tic episodes and no worse than mild nausea, was obtained in 63% in the GRA group and in 79% of the patients in the GRA+PRE group day 1 (P=0.013). Complete response rates on days 1–3 were 16% vs 27% (P=0.251). Significantly less nausea and vomiting was seen with the combination in the first 24 h after cisplatin (P=0.001 and P=0.0003) and during days 1–3 (P=0.005 and 0.044). Patient preference was 51.5% for the combination and 26.5% for granisetron alone, whereas 22% had no preference (P=0.0270). Adverse reactions were mild and comparable; headache and constipation were the ones most frequently reported. Prednisolone significantly improves the antiemetic effect of granisetron in patients receiving cisplatin-based chemotherapy, but the study also emphasizes the poor complete protection rate in patients receiving multiple-day cisplatin-based chemotherapy.     

The antiemetic efficacy of granisetron plus dexamethasone, haloperidol and loracepam in breast cancer patients treated with high-dose chemotherapy with peripheral blood stem-cell support

There has recently been a marked trend to increasing dose intensity in cancer chemotherapy, with or without peripheral blood stem-cell support, which has been associated with a higher frequency of nausea and vomiting. Antiemetic treatment in this setting has not been extensively analysed. From October 1995 to January 1997, prevention of emesis with granisetron 3 mg/12 h IV, dexamethasone 12 mg/24 h IV, haloperidol 0.5 mg/12 h PO, and loracepam 1 mg/24 h PO was instituted in 30 breast cancer patients treated with high-dose chemotherapy (a 4-day intravenous continuous infusion of cyclophosphamide 1500 mg/m² per day, thio-TEPA 125 mg/m² per day and carboplatin 200 mg/m² per day).A total of 30% of the patients (9/30) obtained complete or major protection on the 4 days of chemotherapy treatment (96.7% (29/30) on day 1, 86.7% (26/30) on day 2, 70% (21/30) on day 3, and 50% (15/30) on day 4). On the days following chemotherapy, 46.7% (14/30) presented fewer than two emetic episodes on day 5, 70% (21/30) on day 6, 83.4% (25/30) on day 7 and, 93.3% (28/30) on day 8. This energic antiemetic combination treatment has hardly any effect in the prevention of emesis, providing complete or major protection of 30% for the 4 days of chemotherapy treatment. Further investigation aimed at improving antiemetic treatment results is necessary.     

Impact of initiating antiemetic prophylaxis with palonosetron versus ondansetron on risk of uncontrolled chemotherapy-induced nausea and vomiting in patients with lung cancer receiving multi-day chemotherapy

Purpose  

The purpose of this study is to examine the risk of uncontrolled chemotherapy-induced nausea/vomiting (CINV) among lung cancer patients receiving multi-day chemotherapy and ondansetron- or palonosetron-initiated prophylactic antiemetic regimens in a community oncology setting.     

A double-blind, multicentre comparison of intravenous dolasetron mesilate and metoclopramide in the prevention of nausea and vomiting in cancer patients receiving high-dose cisplatin chemotherapy

The potent serotonin receptor (5-HT₃) antagonists are new highly selective agents for the prevention and control of chemotherapy-induced nausea and vomiting that have been shown to be comparable to or more effective than traditional metoclopramide regimens. This study was designed to compare the antiemetic efficacy of dolasetron and metoclopramide in chemotherapy-naive and non-naive cancer patients receiving high-dose cisplatin-containing chemotherapy. This multicentre, double-blind, randomized trial compared the efficacy and safety of single i.v. doses of dolasetron mesilate salt (1.2 or 1.8 mg/kg) and metoclopramide (7 mg/kg) in 226 patients for the prevention of acute emesis and nausea associated with the administration of high-dose (80 mg/m²) cisplatin. Efficacy and safety were evaluated for 24 h. Complete responses were achieved by 57%, 48%, and 35% of patients given dolasetron mesilate 1.8 mg/kg (P=0.0009 vs metoclopramide), dolasetron mesilate 1.2 mg/kg (P=0.0058 vs metoclopramide), and metoclopramide, respectively. Overall, dolasetron was significantly more effective than metoclopramide for time to first emetic episode, nausea, patient satisfaction, and investigator global assessment of efficacy. Males, chemotherapy-naive patients, and alcoholics had higher response rates. Dolasetron was well tolerated, with mild-to-moderate headache most commonly reported. Twelve percent of patients receiving metoclopramide reported extrapyramidal symptoms compared with 0% of patients receiving dolasetron. In conclusion, dolasetron mesilate was effective for the prevention of CINV with high-dose cisplatin. Single i.v. doses of dolasetron mesilate were more effective than 7 mg/kg metoclopramide in preventing nausea and vomiting induced by highly emetogenic cisplatin-containing chemotherapy. In addition, 1.8 mg/kg dolasetron mesilate consistently produced the highest response rates and appears to be the most effective dose for further clinical development.     

Palonosetron plus dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients receiving multiple-day cisplatin chemotherapy for germ cell cancer

GOALS OF WORK: The aims of this study were to assess the safety and antiemetic efficacy of multiple-day dosing of palonosetron plus dexamethasone in patients receiving highly emetogenic multiple-day cisplatin-based chemotherapy for germ cell tumors. MATERIALS AND METHODS: Forty-one men undergoing 5-day cisplatin-based chemotherapy for testicular cancer received palonosetron 0.25 mg IV once daily 30 min before chemotherapy on days 1, 3, and 5 plus IV dexamethasone 20 mg before chemotherapy on days 1 and 2, and 8 mg PO bid on days 6 and 7 and 4 mg bid on day 8. Safety and efficacy were assessed in 24-h intervals for 9 days. Efficacy endpoints included emesis, intensity of nausea and its interference with patient functioning, and rescue antiemetic use. A subset of patients (n = 11) was studied for electrocardiograph effects and pharmacokinetic evaluation. MAIN RESULTS: This multiple-day antiemetic regimen was safe, with headache and constipation the most common treatment-related adverse events, mostly mild. Neither adverse events nor electrocardiographic changes appeared to increase in frequency, duration, or intensity over time despite a 1.42-fold systemic accumulation of palonosetron with repeated doses. The majority of patients had no emesis at any time throughout days 1-5 (51%) or days 6-9 (83%), had no moderate-to-severe nausea, and did not require rescue medication. Most patients reported that nausea had no significant effect on daily functioning on days 1-4 (72%) and days 5-9 (85%). CONCLUSIONS: Palonosetron on days 1, 3, and 5, along with a regimen of dexamethasone, was safe and well tolerated and effectively controlled both nausea and emesis in patients undergoing 5-day cisplatin-based chemotherapy for testicular cancer.     

Randomized placebo-controlled trial of perindopril in normotensive, normoalbuminuric patients with type 1 diabetes mellitus

Diabetic nephropathy is one of the leading causes of end-stage renal disease. We examined whether ACE inhibitor treatment may have a nephroprotective effect in normotensive insulin-dependent diabetic patients without microalbuminuria and with normal glomerular filtration rate (GFR), and whether any effect was associated with the ACE genotype. In a prospective double-blind randomized study, normotensive patients with type 1 diabetes mellitus with normal serum creatinine and no microalbuminuria were treated with either placebo or perindopril, an ACE inhibitor. Urine albumine/creatinine ratio (ACR), mean blood pressure (MBP) and index of glomerular filtration rate (GFR) based on S-creatinine were determined. ACE genotype was determined by electrophoresis. ACR was higher in the placebo group than in the perindopril group after 4 months, and continued to increase during the study period. After 36 months of observation, ACR in the placebo group was 1.7+/-1.1 mg/mmol, and 0.6+/-0.2 mg/mmol in the ACE-inhibitor-treated group (p<0.001, Mann-Whitney test). During treatment, a significant increase in ACR in the placebo group (p=0.007), Wilcoxon matched paired test) was observed. There were no differences between the groups regarding MBP or GFR. The nephroprotective effects of ACE inhibitor treatment was not associated with the ACE genotype (II, ID, DD).     

阿德福韦酯治疗HBeAg阳性慢性乙型肝炎的疗效和安全性研究

目的评价一种国产阿德福韦酯用于治疗HBeAg阳性慢性乙型肝炎患者的疗效和安全性。方法采用多中心、随机、双盲、安慰剂对照的临床试验,选择HBeAg阳性的慢性乙型肝炎患者211例,按1∶1的比例随机分为阿德福韦酯组和拉米夫定组。完成12周治疗后均进入阿德福韦酯开放治疗期。完成12周和48周治疗时,检测血清HBVDNA及ALT水平。结果治疗12周时阿德福韦酯组（107例）血清HBVDNA水平平均下降2.94log10拷贝/ml,77.6%的受试者血清HBVDNA水平下降≥2log10拷贝/ml或血清HBVDNA≤104拷贝/ml,ALT均值下降76.9IU/L;而安慰剂组（104例）血清HBVDNA水平平均下降0.57log10拷贝/ml,血清HBVDNA水平下降≥2log10拷贝/ml或血清HBVDNA≤104拷贝/ml的受试者比例仅为13.5%,ALT均值下降20.9IU/L。两组血清HBVDNA水平下降值和血清ALT下降值比较,差异均有统计学意义（P〈0.05）。治疗48周时,阿德福韦酯组血清HBVDNA水平平均下降3.54log10拷贝/ml,ALT均值下降100.6IU/L;安慰剂组血清HBVDNA水平平均下降3.28log10拷贝/ml,ALT均值下降92.7IU/L;两组血清HBVDNA水平下降值和血清ALT下降值比较,差异无统计学意义（P〉0.05）。阿德福韦酯组不良事件发生率与安慰剂组相比,差异无统计学意义（P〉0.05）。结论阿德福韦酯治疗HBeAg阳性慢性乙型肝炎可在病毒学及生化学方面取得较好疗效,且安全性良好。     

Intravenous dexamethasone vs placebo as adjunctive therapy to reduce the recurrence rate of acute migraine headaches: a multicenter, double-blinded, placebo-controlled randomized clinical trial

Objectives

Some physicians prescribe corticosteroids as adjunctive therapy for patients with migraine headaches to decrease the rate of rebound headache. The efficacy of this practice has not been tested. Our objective is to determine the efficacy of single-dose dexamethasone as adjunctive therapy for emergency medicine patients with migraine headache in preventing headache recurrence at 3 and 30 days posttreatment.

Methods

From November 2004 to November 2005, we conducted a multicenter, double-blinded, placebo-controlled randomized clinical trial of adult patients who met the International Headache Society definition of migraine headache. After informed consent, patients were randomly assigned to one of two groups: receiving either placebo or 24 mg dexamethasone intravenously. To ensure generalizability, all other aspects of patient care were left to the discretion of the emergency physician. Clinical and demographic information was obtained; and patients were subsequently contacted at both 3 and 30 days to determine headache recurrence, current functional disability, and need for return to the ED. Our primary outcome measures were the recurrence of migraine headache at 3 and 30 days. We used Fisher exact to test for statistical significance.

Results

A total of 115 patients were enrolled, with 16 patients lost to follow-up at 3 days and 3 additional patients lost at 30 days. Baseline characteristics as well as adverse event profiles were equivalent in both study groups. At 3-day follow-up, 45% (95% confidence interval [CI] 31%-60%) of the placebo group had recurrence of their migraine compared with 35% (95% CI 24%-48%) in the dexamethasone group (P = .68). At 30-day follow-up, this relative reduction in migraine recurrence decreased to a 4% difference between the 2 groups (P = .68). Limitations include small sample size and significant proportion lost to follow-up.

Conclusion

A single dose of dexamethasone as adjunctive therapy for migraine headache does not decrease the recurrence of migraines at 3 or 30 days.     

Efficacy of oxycodone/paracetamol for patients with bone-cancer pain: a multicenter, randomized, double-blinded, placebo-controlled trial

What is known and Objective: Bone‐cancer pain is a common and refractory cancer pain. Opioids, on their own, do not control this type of pain well enough, and co‐analgesics are necessary. Methods: Patients with bone metastasis‐related pain at Numeric Rating Scale ≥4 were enrolled to this randomized placebo‐controlled trial. They had also received morphine or transdermal fentanyl patches for at least 1 week. During the 3‐day efficacy phase, patients received placebo or 1–3 tablets of oxycodone/paracetamol (5/325 mg), four times daily for 3 days. All patients kept a daily pain diary. The primary endpoint was the Pain Intensity Difference (PID). Secondary endpoints were cases of breakthrough pain and rescue morphine consumption. Additional analyses included the Short Form‐6 Dimensions (SF‐6D) quality‐of‐life scale and a general impression (GI) of patient satisfaction with treatment at the end of the phase. Results and Discussion: Of the 246 patients in the intent‐to‐treat set, 89·4% completed the 3‐day efficacy phase. PIDs were 0·9 and 0·3 in the oxycodone/paracetamol and placebo groups respectively, on day 1 (P < 0·001), and 1·5 and 0·3 respectively on day 3 (P < 0·001). Thirty‐eight patients in the treatment group, and 58 in the placebo group, suffered breakthrough pain on day 3 (P < 0·001). The SF‐6D score decreased to 21·2 ± 2·5 in the oxycodone/paracetamol group at the end of the phase (P = 0·001). In the oxycodone/paracetamol group, 67% rated GI as good, very good, or excellent. What is new and Conclusion: Patients with bone‐cancer pain, already on opioids, obtain clinically important, additional pain‐control, with regular oxycodone/paracetamol dosing.     

Efficacy of the NMDA-receptor antagonist memantine in patients with chronic phantom limb pain--results of a randomized double-blinded,placebo-controlled trial

Phantom limb pain (PLP) associated neuroplastic changes are partly mediated by excitatory amino acids at NMDA receptor sites. This study was undertaken to deduce if NMDA-receptor antagonists may be effective in patients with chronic PLP. Therefore a four week double-blinded, randomized placebo-controlled trial was performed to evaluate the efficacy of 30 mg memantine/day, an orally administrable NMDA receptor antagonist.Thirty-six patients, 18 per group, with a history of at least 12 months PLP and an average pain of at least 4 on the 11-point numeric rating scale (NRS) were enrolled. The patients completed a standardized questionnaire before the trial. PLP intensity and the level of eight complaints were assessed during the trial. Number needed to treat (NNT) was calculated based on the average PLP during the 3rd week (steady state). In both groups, PLP declined significantly in comparison with the baseline (verum: 5.1 (+/-2.1) to 3,8 (+/-2,3), placebo from 5.1 (+/-2.0) to 3.2 (+/-1,46) NRS) without a re-rising of the PLP during the washout period. Mean pain relief was 47% in the memantine group (10 patients reported more than 50% relief), 40% in the placebo group (6>50%): NNT were 4.5 (KI: 2.1-10.6). Analysis of covariance demonstrated a significant impact only on the prior PLP intensity, but no treatment effect. Two patients have demonstrated long-term pain relief under memantine until now (16 months). The total number of slight adverse events were comparable in both groups, but the overall number of severe events was higher in the memantine group (P<0.05). This trial failed to demonstrate a significant clinical benefit of the NMDA-receptor antagonist memantine in chronic PLP. The administration of a higher dosage is probably not tolerable.