Rachel P. Riechelmann

Effectiveness of Specialized Palliative Care : A Systematic Review

CONTEXTnSpecialized palliative care teams are increasingly providing care for the terminally ill. However, the impact of such teams on quality of life, satisfaction with care, and economic cost has not been examined systematically using detailed criteria for study quality.nnnOBJECTIVEnTo systematically review the evidence for effectiveness of specialized palliative care.nnnDATA SOURCESnWe performed a keyword search of the following databases from their inception to January 2008: MEDLINE, Ovid Healthstar, CINAHL, EMBASE, and the Cochrane Central Register of Controlled Trials.nnnSTUDY SELECTIONnWe included all randomized controlled trials in which specialized palliative care was the intervention and for which outcomes included quality of life, satisfaction with care, or economic cost.nnnDATA EXTRACTIONnData on population, intervention, outcome, methods, and methodological quality were extracted by 2 investigators using standardized criteria.nnnRESULTSnOf 396 reports of randomized controlled trials, 22 met our inclusion criteria. There was most consistent evidence for effectiveness of specialized palliative care in improvement of family satisfaction with care (7 of 10 studies favored the intervention). Only 4 of 13 studies assessing quality of life and 1 of 14 assessing symptoms showed a significant benefit of the intervention; however, most studies lacked statistical power to report conclusive results, and quality-of-life measures were not specific for terminally ill patients. There was evidence of significant cost savings of specialized palliative care in only 1 of the 7 studies that assessed this outcome. Methodological limitations were identified in all trials, including contamination of the control group, failure to account for clustering in cluster randomization studies, and substantial problems with recruitment, attrition, and adherence.nnnCONCLUSIONSnThe evidence for benefit from specialized palliative care is sparse and limited by methodological shortcomings. Carefully planned trials, using a standardized palliative care intervention and measures constructed specifically for this population, are needed.

Symptom and medication profiles among cancer patients attending a palliative care clinic

BackgroundPatients with advanced cancer frequently experience distressful symptoms and receive numerous medications. We describe the symptomatology and medication profile of ambulatory cancer patients receiving exclusively supportive care at the Princess Margaret Hospital.Materials and methodsThis was a retrospective, cross-sectional study. We reviewed the charts of consecutive adult cancer patients attending palliative care clinics and who were no longer receiving cancer-directed therapy. From the medical records, we collected information about self-reported symptoms [screened for with the numerical Edmonton symptom assessment system (ESAS) scale; range, 0–10, with 10=worst symptom] and medication profiles. Summary statistics were used to describe the results.ResultsTwo hundred fifty five patients met the inclusion criteria. The most frequent self-reported symptoms of any severity were fatigue (77%), pain (75%), and lack of appetite (66%). These were also the most severe symptoms: fatigue (median ESAS score=7), pain (median ESAS=5), and lack of appetite (median ESAS=5). The median number of medications per patient after consultation in the palliative care service was 6, and the most common classes of drugs prescribed were opioids (67%), laxatives/stool softeners (54%), corticosteroids (41%), and acetaminophen (41%). Palliative care physicians made at least one medication change in 75% of the patients, with the most frequent change being the addition of new medication(s); dexamethasone was the most commonly added individual drug (18% of the patients).ConclusionAmong patients with advanced cancer not receiving antineoplastic therapy, the most frequent and severe symptoms were fatigue, pain, and lack of appetite. The medication profile represented drugs that could both alleviate and contribute to these symptoms. Audit of patient symptoms and medication prescription in palliative care may inform clinical practice and help the development of research specific to patient symptoms.

Potential Drug Interactions in Cancer Patients Receiving Supportive Care Exclusively

Cancer patients at the end of life often take many medications and are at risk for drug interactions. The purpose of this study was to describe the epidemiology of potential drug interactions in cancer patients receiving supportive care exclusively. We retrospectively reviewed the charts of consecutive adult cancer outpatients attending palliative care clinics at the Princess Margaret Hospital, Toronto, Canada. Drugs were screened for interactions by the Drug Interaction Facts software, which classifies interactions by levels of severity (major, moderate, and minor) and scientific evidence (1-5, with 1=the strongest level of evidence). Among 372 eligible patients, 250 potential drug interactions were identified in 115 patients (31%, 95% confidence interval 26%-36%). The most common involved warfarin and phenytoin. Most interactions were classified as being of moderate severity (59%) and 42% of them were supported by Levels 1-3 of evidence. In multivariable analysis, increasing age (P<0.001), presence of comorbidity (P=0.001), cancer type (brain tumors, P<0.001), and increasing number of drugs (P<0.001) were associated with risk of drug interactions. Potential drug interactions are common in palliative care and mostly involve warfarin and anticonvulsants. Older patients, those with comorbid conditions, brain tumor patients, and those taking many medications are at greater risk of drug interactions.

Phase II trial of mirtazapine for cancer-related cachexia and anorexia.

We performed an open-label single-institution phase II trial of mirtazapine (15-30 mg by mouth [po] every day [qd]), a tetracyclic antidepressant that may lead to weight gain, for 8 weeks in nondepressed patients with cancer-related cachexia/anorexia (CRCA). The primary end point was the proportion of patients who gained ≥1 kg at week 4. Secondary end points were quality of life and appetite. From June 2006 to July 2007, 17 of 58 eligible patients were enrolled. On intention-to-treat analysis at week 4, 4 of 17 patients (24%) gained 1 kg or more, 1 patient maintained weight (gain of 400 g) and 2 patients lost weight (800 g and 1.2 kg); 24% and 6% improved appetite and health-related quality of life (HQOL), respectively. Mirtazapine is a promising agent for the treatment of CRCA.

Disclosure of Conflicts of Interest by Authors of Clinical Trials and Editorials in Oncology

PURPOSEnThere is concern that financial relationships between sponsors and investigators may bias research results. Our objective was to evaluate the epidemiology of conflicts of interest (COIs) among authors of clinical trials and editorials in oncology and the relationship between COI disclosure and source of funding.nnnMETHODSnWe did a cross-sectional survey of clinical trials and editorials of anticancer agents and supportive care medications published in the Journal of Clinical Oncology (JCO) during a 1-year period.nnnRESULTSnOf 1,533 articles published in JCO between January 1, 2005, and January 31, 2006, 332 met our inclusion criteria; 289 (87%) were clinical trials, and 43 (13%) were editorials. The pharmaceutical industry entirely or partially funded 44% of the clinical trials. At least one COI was disclosed in 69% of clinical trials and 51% of editorials. The most common types of COI reported by authors were consultancy fees, honoraria, and research funds. The highest monetary levels of interest reported by authors were for research grants, but the majority of authors with COIs received less than US

Sorafenib for metastatic renal cancer: the Princess Margaret experience.

10,000. In multivariable analysis, authors of clinical trials conducted in North America (North America v Europe: odds ratio [OR] = 2.9, P = .002) and authors of trials funded entirely (industry only v nonprofit: OR = 13.8, P < .001) or partially (both industry and nonprofit v nonprofit only: OR = 5.8, P < .001) by industry were more likely to report personal COIs.nnnCONCLUSIONnCOIs are common in clinical cancer research and usually take the form of consultancy fees, honoraria, and research funds. Source of study funding was significantly associated with COI disclosure.

Use of unnecessary medications by patients with advanced cancer: cross-sectional survey

Objective:Sorafenib, an oral multikinase inhibitor, prolonged progression-free survival when compared with placebo, as second-line therapy for patients with metastatic renal carcinoma (MRC). Grade 3/4 adverse events were reported in 12% of patients. This study presents sorafenibs efficacy and safety in a less selected cohort of patients enrolled in an expanded access program. Methods:Patients with MRC received sorafenib 400 mg twice daily until disease progression. Tumor response was evaluated by RECIST criteria. Adverse events were graded by NCI common toxicity criteria. Results:From November 2005 to August 2006, 58 patients were enrolled. The median progression-free survival was 7.5 months (95% CI: 5.4–11.3), and the best responses among 54 patients were 11 (20%) confirmed partial responses, 15 (28%) stable diseases for ≥6 months; 10 patients (18%) had early progression at 8 weeks. Grade 3/4 adverse events occurred in 37 patients (64%; 95% CI: 50%–76%), the most frequent being skin rash in 17 patients (29%), and hand-foot syndrome in 9 patients (15%). Thirty-six (62%) patients required dose reductions and/or treatment interruptions. Conclusions:Sorafenib is effective in a less selected patient population with MRC but leads to more toxicity than described previously.

Self-Reported Conflicts of Interest of Authors, Trial Sponsorship, and the Interpretation of Editorials and Related Phase III Trials in Oncology

BackgroundCancer patients at the end of life take numerous medications. However, it has not been assessed what proportion of patients take unnecessary medications and which patients are at risk for doing so.MethodsCross-sectional survey of medications utilized by terminally ill ambulatory cancer patients, with the aim of identifying medications considered unnecessary as per explicit criteria. The criteria took into account whether drugs could benefit patients with terminal cancer.ResultsAmong 87 patients, 21 (24%, 95% confidence interval [CI] 15.6–34.5%) were taking at least one unnecessary medication, the most common being gastric protectors. In multivariable analyses, patients with Charlson Comobidity Indexu2009≤u20091 (OR: 4.49, CI95% 1.32–15.26; pu2009=u20090.01) or whose medication list had not been reconciled by physicians (OR: 6.38, CI95% 1.21–33.40; pu2009=u20090.02) were more likely to use an unnecessary medication.ConclusionPatients with advanced cancer take many medications considered unnecessary. Medication reconciliation should be performed routinely for these patients.

Phase II trial of metformin and paclitaxel for patients with gemcitabine-refractory advanced adenocarcinoma of the pancreas.

PURPOSEnGrowing participation by industry in cancer research has resulted in increased reporting of conflicts of interest (COI). We aimed to test any association between authors conclusions and self-reported COI or trial sponsorship in cancer studies.nnnMETHODSnEditorials and related phase III trials published in six clinical oncology journals in the last 3.5 years were analyzed independently by two investigators who classified study conclusions according to authors endorsement of the experimental therapy. Logistic regression multivariable models were used to assess predictors of favorable conclusions of editorialists and of phase III authors.nnnRESULTSnFrom January 2008 to October 2011, 1,485 articles were retrieved: 150 phase III trials and 150 editorials were eligible. Among the phase III trials, 82 (54.7%) had positive results, and 78 (52.0%) were entirely or partially funded by industry. Any COI were disclosed in 103 phase III trials (68.7%) and in 71 editorials (47.3%). Multivariable analysis showed that phase III trial results were the only significant predictor for a positive conclusion by trial authors (odds ratio [OR], 92.2; 95% CI, 19.7 to 431.6; P < .001). Sponsorship did not predict for positive conclusion by phase III authors (OR, 0.86; 95% CI, 0.3 to 2.5; P = .788). The only factor associated with positive conclusions by editorial authors was a positive conclusion by phase III trial authors (OR, 36.3; 95% CI, 6.8 to 194.2; P < .001).nnnCONCLUSIONnThe interpretation of recently published phase III cancer trials by their authors or by editorialists was not influenced by financial relationships or industry sponsorship. Increased awareness of COI policies may have led to more integrity in cancer research reporting.

The impact of complete chemotherapy stop on the overall survival of patients with advanced colorectal cancer in first-line setting: A meta-analysis of randomized trials.

Background In patients with adenocarcinoma of the pancreas, there are no standard second-line regimens. Many pre-clinical studies have shown that metformin alone or when combined with paclitaxel has antitumour effects on this tumour. We have tested here the combination of paclitaxel and metformin for patients with gemcitabine-refractory pancreatic cancer. Methods An uncontrolled phase II trial was carried out based on a two–stage Simon’s design, with metformin and paclitaxel for patients with locally advanced or metastatic pancreatic cancer whose disease had progressed during first line treatment with a gemcitabine-based regimen. The primary endpoint was the disease control rate at eight weeks as per response evaluation criteria in solid tumours (RECIST) 1.1. Patients received paclitaxel 80 mg/m2 weekly for three weeks every 28 days and metformin 850 mg p.o. t.i.d. continuously until progression or intolerance state was reached. Results Twenty patients were enrolled from July 2011 to January 2014: N = 6 (31.6%) achieved the primary endpoint, with all presenting stable disease. Median overall survival (OS) was 128 days (range 17–697) and the median progression free survival (PFS) was 44 days (range 14–210). Eight patients (40%) presented treatment-related G3-4 toxicities with the most common one being diarrhoea. Conclusions Despite the encouraging pre-clinical evidence of the antitumour activity of metformin in adenocarcinoma of the pancreas, the primary endpoint of the disease control rate was not met. Besides, the treatment combination was poorly tolerated and could not be studied further. This study highlights the importance of performing clinical trials to reassure preclinical or observational data.