Marko Popovic

Efficacy and safety of palonosetron for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV): a systematic review and meta-analysis of randomized controlled trials

PurposePalonosetron, a 5-hydroxytryptamine 3 receptor antagonist (5-HT3RA) with a strong binding affinity and long half-life, has been used in numerous trials for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV). We systematically reviewed the efficacy and safety of palonosetron compared to other 5-HT3RAs in CINV prophylaxis.MethodsA literature search of Ovid MEDLINE, EMBASE, and CENTRAL was conducted to identify randomized controlled trials (RCTs) comparing palonosetron to other 5-HT3RAs in CINV prophylaxis. Primary endpoints were the percentage of patients achieving a complete response (CR), complete control (CC), no emesis, no nausea, or taking no rescue medications. Secondary endpoints were the percentage of patients suffering from 5-HT3RA-related adverse events.ResultsSixteen RCTs were identified with 2,896 patients randomized to palonosetron and 3,187 patients randomized to other 5-HT3RAs. Palonosetron was consistently statistically superior in CR, CC, no emesis, or no nausea and was sometimes superior in no rescue medication. Subgroup analyses demonstrated similarity in efficacy between highly and moderately emetogenic chemotherapy cohorts. In the acute phase, statistical superiority of palonosetron was found for trials that did not allow dexamethasone; conversely, RCTs that administered dexamethasone to all patients were nonsignificant. Palonosetron was statistically significantly safer in dizziness and mean QTc interval change and similar in constipation, headache, and diarrhea. Clinical superiority of palonosetron was reached in 3 of 19 analyzed efficacy and safety endpoints.ConclusionsPalonosetron is safer and more efficacious than other 5-HT3RAs. Future antiemetic guidelines should discuss the merits of including palonosetron as a first-line treatment.

Efficacy of olanzapine for the prophylaxis and rescue of chemotherapy-induced nausea and vomiting (CINV): a systematic review and meta-analysis

PurposeOlanzapine is a potent antipsychotic medication that inhibits a wide variety of receptors. It has been used in trials for the prophylaxis and rescue of chemotherapy-induced nausea and vomiting (CINV). This study systematically investigates the efficacy of olanzapine in relation to other antiemetics in the prophylaxis and rescue of CINV.MethodsA literature search of Ovid MEDLINE, EMBASE, and CENTRAL was conducted to identify randomized controlled trials (RCTs) comparing olanzapine to other standard antiemetics for either prevention or rescue. The primary endpoints were the percentage of patients achieving no emesis or no nausea, in the acute, delayed, and overall phases.ResultsTen RCTs in the preventative setting and three RCTs in the breakthrough setting were identified. Subgroup analysis demonstrated a similar degree of benefit from a 5- and 10-mg dose of olanzapine for the no emesis endpoint in the overall phase. In the prophylaxis setting, olanzapine was statistically superior in five of six endpoints and clinically superior in four of six endpoints. In the breakthrough setting, olanzapine was statistically and clinically superior in the only endpoint analyzed: no emesis.ConclusionOlanzapine is more efficacious than other standard antiemeticsxa0for the rescue of CINV and its inclusion improves control in the prevention setting. Given the possible reduction in side effects, the use of a 5-mg dose of olanzapine should be considered. Future RCTs should compare the 5-mg versus the 10-mg dosages further and report on the efficacy and percentage of patients developing side effects. Further analyses should be done without the influence of corticosteroids.

Efficacy and Safety of Femtosecond Laser-Assisted Cataract Surgery Compared with Manual Cataract Surgery: A Meta-Analysis of 14 567 Eyes

TOPICnTo investigate the efficacy and safety of femtosecond laser-assisted cataract surgery (FLACS) relative to manual cataract surgery (MCS).nnnCLINICAL RELEVANCEnIt is unclear whether FLACS is more efficacious and safe relative to MCS.nnnMETHODSnA literature search of MEDLINE, EMBASE, and Scopus from 2007 to March 2016 was conducted. Studies containing both FLACS and MCS arms that reported on relevant efficacy and/or safety parameters were included. Weighted mean differences (WMDs) and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated.nnnRESULTSnFrom 2802 screened articles, 14u2009567 eyes from 15 randomized controlled trials and 22 observational cohort studies were included. For primary visual and refractive outcomes, no statistically significant difference was detected between FLACS and MCS in uncorrected distance visual acuity (WMD,xa0-0.02; 95% CI,xa0-0.04 to 0.01; Pxa0= 0.19), corrected distance visual acuity (WMD,xa0-0.01; 95% CI,xa0-0.02 to 0.01; Pxa0= 0.26), and mean absolute error (WMD,xa0-0.02; 95% CI,xa0-0.07 to 0.04; Pxa0= 0.57). In terms of secondary surgical end points, there was a statistically significant difference in favor of FLACS over MCS for effective phacoemulsification timexa0(WMD,xa0-3.03; 95% CI,xa0-3.80 toxa0-2.25; P < 0.001), capsulotomy circularity (WMD, 0.16; 95% CI, 0.11-0.21; P < 0.001), postoperative central corneal thickness (WMD,xa0-6.37; 95% CI,xa0-11.88 toxa0-0.86; Pxa0= 0.02), and corneal endothelial cell reduction (WMD,xa0-55.43; 95% CI,xa0-95.18 toxa0-15.69; Pxa0= 0.006). There was no statistically significant difference between FLACS and MCS for total surgery time (WMD, 1.25; 95% CI,xa0-0.08 to 2.59; Pxa0= 0.07), capsulotomy circularity using a second formula (WMD, 0.05; 95% CI,xa0-0.01 to 0.12; Pxa0= 0.10), and corneal endothelial cell count (WMD, 73.39; 95% CI,xa0-6.28 to 153.07; Pxa0= 0.07). As well, there was a significantly higher concentration of prostaglandins after FLACS relative to MCS (WMD, 198.34; 95% CI, 129.99-266.69; Pxa0<xa00.001). Analysis of safety parameters revealed that there were no statistically significant differences in the incidence of overall complications between FLACS and MCS (RR, 2.15; 95% CI, 0.74 to 6.23; Pxa0= 0.16); however, posterior capsular tears were significantly more common in FLACS versus MCS (RR, 3.73; 95% CI, 1.50-9.25; Pxa0= 0.005).nnnCONCLUSIONSnThere were no statistically significant differences detected between FLACS and MCS in terms of patient-important visual and refractive outcomes and overall complications. Although FLACS did show a statistically significant difference for several secondary surgical outcomes, it was associated with higher prostaglandin concentrations and higher rates of posterior capsular tears.

Original articleEfficacy and Safety of Femtosecond Laser-Assisted Cataract Surgery Compared with Manual Cataract Surgery: A Meta-Analysis of 14 567 Eyes

TOPICnTo investigate the efficacy and safety of femtosecond laser-assisted cataract surgery (FLACS) relative to manual cataract surgery (MCS).nnnCLINICAL RELEVANCEnIt is unclear whether FLACS is more efficacious and safe relative to MCS.nnnMETHODSnA literature search of MEDLINE, EMBASE, and Scopus from 2007 to March 2016 was conducted. Studies containing both FLACS and MCS arms that reported on relevant efficacy and/or safety parameters were included. Weighted mean differences (WMDs) and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated.nnnRESULTSnFrom 2802 screened articles, 14u2009567 eyes from 15 randomized controlled trials and 22 observational cohort studies were included. For primary visual and refractive outcomes, no statistically significant difference was detected between FLACS and MCS in uncorrected distance visual acuity (WMD,xa0-0.02; 95% CI,xa0-0.04 to 0.01; Pxa0= 0.19), corrected distance visual acuity (WMD,xa0-0.01; 95% CI,xa0-0.02 to 0.01; Pxa0= 0.26), and mean absolute error (WMD,xa0-0.02; 95% CI,xa0-0.07 to 0.04; Pxa0= 0.57). In terms of secondary surgical end points, there was a statistically significant difference in favor of FLACS over MCS for effective phacoemulsification timexa0(WMD,xa0-3.03; 95% CI,xa0-3.80 toxa0-2.25; P < 0.001), capsulotomy circularity (WMD, 0.16; 95% CI, 0.11-0.21; P < 0.001), postoperative central corneal thickness (WMD,xa0-6.37; 95% CI,xa0-11.88 toxa0-0.86; Pxa0= 0.02), and corneal endothelial cell reduction (WMD,xa0-55.43; 95% CI,xa0-95.18 toxa0-15.69; Pxa0= 0.006). There was no statistically significant difference between FLACS and MCS for total surgery time (WMD, 1.25; 95% CI,xa0-0.08 to 2.59; Pxa0= 0.07), capsulotomy circularity using a second formula (WMD, 0.05; 95% CI,xa0-0.01 to 0.12; Pxa0= 0.10), and corneal endothelial cell count (WMD, 73.39; 95% CI,xa0-6.28 to 153.07; Pxa0= 0.07). As well, there was a significantly higher concentration of prostaglandins after FLACS relative to MCS (WMD, 198.34; 95% CI, 129.99-266.69; Pxa0<xa00.001). Analysis of safety parameters revealed that there were no statistically significant differences in the incidence of overall complications between FLACS and MCS (RR, 2.15; 95% CI, 0.74 to 6.23; Pxa0= 0.16); however, posterior capsular tears were significantly more common in FLACS versus MCS (RR, 3.73; 95% CI, 1.50-9.25; Pxa0= 0.005).nnnCONCLUSIONSnThere were no statistically significant differences detected between FLACS and MCS in terms of patient-important visual and refractive outcomes and overall complications. Although FLACS did show a statistically significant difference for several secondary surgical outcomes, it was associated with higher prostaglandin concentrations and higher rates of posterior capsular tears.

EORTC QLQ-BR23 and FACT-B for the assessment of quality of life in patients with breast cancer: a literature review

BACKGROUNDnThis study aims to compare the development, characteristics and validity of two widely used tools in the breast cancer population, the EORTC QLQ-BR23 and the FACT-B.nnnMETHODSnA literature search was conducted using Ovid MEDLINE, OLDMEDLINE, Embase, Embase Classic and the Cochrane Central Register of Controlled Trials to identify relevant studies.nnnRESULTSnBoth tools were found to be reliable and valid. The QLQ-BR23 focuses on physical function, whereas the FACT-B emphasizes emotional well-being. Scoring, item format, organization and response options differ between questionnaires.nnnCONCLUSIONnOverall, both questionnaires are effective in assessing breast cancer-specific quality of life. Clear similarities and differences between the two tools exist. Decision-making between the questionnaires should be based on the purpose and design of the study.

Efficacy and safety of olanzapine for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) as reported in phase I and II studies: a systematic review

IntroductionOlanzapine is an atypical antipsychotic drug that inhibits serotonergic, dopaminergic, alpha-1 adrenergic, histaminic, and muscarinic receptors. Several phase I and II trials have been published documenting the use of olanzapine in controlling chemotherapy-induced nausea and vomiting (CINV). This review aims to summarize all phase I and II trials that reported on olanzapine for the prophylaxis of CINV.MethodsA literature search was conducted in Ovid MEDLINE from 1946 to July week 1 2015, Embase Classic and Embase from 1947 to 2015 week 28, and the Cochrane Central Register of Controlled Trials up until June 2015. Phase I and II trials reporting on olanzapine for the prophylaxis for CINV were included if they reported on at least one of four primary endpoints: complete response (CR), complete control (CC), no nausea, and no emesis. Other endpoints of interest included the safety of olanzapine as measured by the M.D. Anderson Symptom Inventory.ResultsAcross the seven included studies, there were a total of 201 patients. The CR across four studies was 97.2, 83.1, and 82.8xa0% for the acute, delayed, and overall phases, respectively. The CC for acute, delayed, and overall phases was 92.5, 87.5, and 82.5xa0%, respectively. The overall no nausea rate was 92.7, 71.8, and 70.6xa0% for the acute, delayed, and overall phases, respectively. The overall no emesis rates for the acute, delayed, and overall phases were 100, 94.5, and 90.4xa0%, respectively. Fatigue, drowsiness, and disturbed sleep were common side effects.ConclusionOlanzapine is efficacious and safe when used as a prophylaxis for CINV.

Update on the management of chemotherapy-induced nausea and vomiting – focus on palonosetron

Purpose Nausea and vomiting are major adverse effects of chemotherapy and can greatly impact patients’ quality of life. Although chemotherapy-induced nausea and vomiting (CINV) prevalence is high, treatment remains difficult. Palonosetron is a 5-hydroxytryptamine receptor antagonist (5-HT3RA) approved for treatment of CINV. The purpose of this review is to discuss existing and emerging therapeutic options, and examine studies focusing on palonosetron with regards to efficacy, pharmacology, tolerability, safety, and patient-derived outcomes. Methods A literature search was conducted using Ovid MEDLINE and EMBASE to identify relevant studies using palonosetron alone or in combination with other antiemetics. Studies were extracted if they included complete response (CR), complete control (CC), no nausea, no vomiting, and no rescue medications as an endpoint. Studies were also included if safety endpoints were examined. Results Palonosetron alone has been shown to improve CR and CC rates for patients receiving low, moderate, or high emetogenic chemotherapy. Rates were further improved with the addition of dexamethasone, a corticosteroid. Furthermore, the addition of neurokinin-1 receptor antagonists, such as netupitant markedly improved efficacy profiles compared to palonosetron alone. Aprepitant is an antiemetic that has exhibited positive results in combination with palonosetron. Recently, a new drug consisting of netupitant and palonosetron (NEPA) has demonstrated significantly more efficacious prevention of CINV. Regardless of the combination, palonosetron has been well tolerated. The most common adverse events were constipation, headache, fatigue, and dizziness, with the majority of patients describing them as only mild or moderate. Conclusion Palonosetron, alone or with other antiemetics, has improved CINV treatment due to its ability to significantly reduce delayed phases of CINV, compared to similar 5-HT3RAs. Palonosetron is both more effective than first generation 5-HT3RAs and safer, as it results in a smaller prolongation of the QTc interval, compared to other 5-HT3RAs.

The accuracy of clinicians’ predictions of survival in advanced cancer: a review

The process of formulating an accurate survival prediction is often difficult but important, as it influences the decisions of clinicians, patients, and their families. The current article aims to review the accuracy of clinicians predictions of survival (CPS) in advanced cancer patients. A literature search of Cochrane CENTRAL, EMBASE, and MEDLINE was conducted to identify studies that reported clinicians prediction of survival in advanced cancer patients. Studies were included if the subjects consisted of advanced cancer patients and the data reported on the ability of clinicians to predict survival, with both estimated and observed survival data present. Studies reporting on the ability of biological and molecular markers to predict survival were excluded. Fifteen studies that met the inclusion and exclusion criteria were identified. Clinicians in five studies underestimated patients survival (estimated to observed survival ratio between 0.5 and 0.92). In contrast, 12 studies reported clinicians overestimation of survival (ratio between 1.06 and 6). CPS in advanced cancer patients is often inaccurate and overestimated. Given these findings, clinicians should be aware of their tendency to be overoptimistic. Further investigation of predictive patient and clinician characteristics is warranted to improve clinicians ability to predict survival.

Breakthrough cancer pain: a comparison of surveys with European and Canadian patients

IntroductionBreakthrough cancer pain is defined as a transient exacerbation of pain that occurs spontaneously or in response to a trigger, despite stable and controlled background pain. Breakthrough pain often causes significant functional impairments for patients and can decrease quality of life.ObjectiveThe objective of the study was to determine differences between breakthrough cancer pain incidence and management in Canada and Europe.MethodsData collected from previous studies of breakthrough cancer pain in Canada and Europe was compared. A standard survey with identical inclusion/exclusion criteria was utilized for both patient populations.ResultsBoth groups of patients had a similar number and duration of breakthrough pain episodes, and similar pain intensity and pain interference with their daily activities. European patients reported better analgesic efficacy and satisfaction with management, and a greater percentage of European patients were prescribed a transmucosal fentanyl formulation (19.1 vs 2.9xa0%). More European patients (55xa0%) than Canadian patients (32.5xa0%) took their rescue medication every time they had a breakthrough pain episode.ConclusionsBreakthrough cancer pain in both Canadian and European patients greatly impacts their daily living, and both groups of patients had similar experiences with breakthrough cancer pain. Currently, this pain is not adequately managed for many patients. The role for new analgesic treatments in management of breakthrough cancer pain needs further study.

A prospective study of gastrointestinal radiation therapy-induced nausea and vomiting

ObjectiveNausea and vomiting are common side effects from radiotherapy that can interfere with gastrointestinal (GI) cancer patients’ quality of life (QOL). A prospective study among patients with GI cancers was conducted to document the timing, incidence and risk factors of radiation therapy-induced nausea and vomiting (RINV).MethodsForty-eight patients planned to receive curative or palliative intent abdominal and/or pelvic radiotherapy alone or with concomitant chemoradiotherapy were followed prospectively. All episodes of nausea, vomiting, retching and antiemetic use were recorded daily for the entire treatment period and for the week following completion of therapy. QOL was assessed weekly using the Functional Living Index—Emesis Quality of Life Tool and the EORTC QLQ-C30 core questionnaire.ResultsNausea occurred in 83xa0% of patients and emesis in 54xa0%. Pancreatic cancer was significantly correlated to higher proportions of nausea and emesis (pu2009=u20090.002 and pu2009=u20090.0003) compared to other primary sites. There were no significant difference between concomitant chemoradiotherapy and radiotherapy only patients for nausea and emesis. Patients had significantly greater proportions of RINV during the first, second and fifth weeks of treatment and during the first week following treatment. Vomiting was found to impair patients’ usual recreation or leisure activities and enjoyment of their meals. Worse physical, role and social functioning and greater fatigue and appetite loss over the course of treatment correlated directly with the timing of RINV symptoms.ConclusionRINV worsened QOL and was experienced even after treatment was completed; physicians should therefore be cognizant and monitor patients in the week following radiotherapy. Concomitant chemoradiotherapy should potentially be included in the moderate emetogenic risk category.