METHODS: We searched PubMed, Embase and the Cochrane Central systematically for the randomised control trials (RCTs) of interventions for preventing OM. Network meta-analysis (NMA) was performed to estimate risk ratios (RR) and 95% confidence intervals (CI) from both direct and indirect evidence. The primary outcome was any grade of OM. Secondary outcomes were mild-moderate OM, severe OM and adverse events, such as taste disturbance and gastrointestinal adverse events. This study was registered with PROSPERO, number CRD42016052489.
RESULTS: A total of 29 RCTs with 2348 patients (median age, 56.1 years; 57.5% male) were included. Cryotherapy was associated with a significantly lower risk of OM than control (RR 0.51, 95% CI 0.38 to 0.68), and zinc sulphate (RR 0.47, 95% CI 0.23 to 0.97), but not significantly lower than sucralfate and palifermin. No significant differences were observed between cryotherapy and control for taste disturbance and gastrointestinal adverse events. Palifermin was associated with the highest risk of taste disturbance.
CONCLUSIONS: This NMA suggests that cryotherapy was the most effective intervention for preventing chemotherapy-induced OM with a safety profile similar to control, but not significantly lower than sucralfate and palifermin. Large RCTs are needed to confirm these findings.
MATERIALS AND METHODS: Participants were 303 consecutive adult cancer patients undergoing chemotherapy in an academic medical center. The short form Memorial Symptom Assessment Scale (MSAS-SF), which covers three domains of symptoms (global distress, physical- and psychological symptoms) was used to cross-sectionally measure symptom frequency and associated distress via self-reporting. One-way ANOVA and t-tests were used to test mean differences among MSAS-SF subscale scores.
RESULTS: Complete data were available for 303 patients. The mean number of symptoms was 14.5. The five most prevalent were fatigue, dry mouth, hair loss, drowsiness and lack of appetite. Overall, symptom burden and frequency were higher than in other published MSAS-SF studies. Higher symptom frequency was also found to be significantly related to greater distress in cancer patients undergoing chemotherapy.
CONCLUSIONS: Patients undergoing chemotherapy suffer from multiple physical and psychological symptoms. Better symptom control or palliative care is needed. Greater frequency of reported symptoms may also indicate a subconscious bid by patients for care and reassurance - thus tailored intervention to manage distress should be offered.
METHODS: In this double-blind, phase 3 trial, we randomly assigned 556 patients with previously untreated, EGFR mutation-positive (exon 19 deletion or L858R) advanced NSCLC in a 1:1 ratio to receive either osimertinib (at a dose of 80 mg once daily) or a standard EGFR-TKI (gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily). The primary end point was investigator-assessed progression-free survival.
RESULTS: The median progression-free survival was significantly longer with osimertinib than with standard EGFR-TKIs (18.9 months vs. 10.2 months; hazard ratio for disease progression or death, 0.46; 95% confidence interval [CI], 0.37 to 0.57; P<0.001). The objective response rate was similar in the two groups: 80% with osimertinib and 76% with standard EGFR-TKIs (odds ratio, 1.27; 95% CI, 0.85 to 1.90; P=0.24). The median duration of response was 17.2 months (95% CI, 13.8 to 22.0) with osimertinib versus 8.5 months (95% CI, 7.3 to 9.8) with standard EGFR-TKIs. Data on overall survival were immature at the interim analysis (25% maturity). The survival rate at 18 months was 83% (95% CI, 78 to 87) with osimertinib and 71% (95% CI, 65 to 76) with standard EGFR-TKIs (hazard ratio for death, 0.63; 95% CI, 0.45 to 0.88; P=0.007 [nonsignificant in the interim analysis]). Adverse events of grade 3 or higher were less frequent with osimertinib than with standard EGFR-TKIs (34% vs. 45%).
CONCLUSIONS: Osimertinib showed efficacy superior to that of standard EGFR-TKIs in the first-line treatment of EGFR mutation-positive advanced NSCLC, with a similar safety profile and lower rates of serious adverse events. (Funded by AstraZeneca; FLAURA ClinicalTrials.gov number, NCT02296125 .).
OBJECTIVE: This review aimed to summarize the current evidence base of reported utility values for chemotherapy-related ADEs.
METHODS: A structured electronic search combining terms for utility, utility valuation methods and generic terms for cancer treatment was conducted in MEDLINE and EMBASE in June 2011. Inclusion criteria were: (1) elicitation of utility values for chemotherapy-related ADEs and (2) primary data. Two reviewers identified studies and extracted data independently. Any disagreements were resolved by a third reviewer.
RESULTS: Eighteen studies met the inclusion criteria from the 853 abstracts initially identified, collectively reporting 218 utility values for chemotherapy-related ADEs. All 18 studies used short descriptions (vignettes) to obtain the utility values, with nine studies presenting the vignettes used in the valuation exercises. Of the 218 utility values, 178 were elicited using standard gamble (SG) or time trade-off (TTO) approaches, while 40 were elicited using visual analogue scales (VAS). There were 169 utility values of specific chemotherapy-related ADEs (with the top ten being anaemia [34 values], nausea and/or vomiting [32 values], neuropathy [21 values], neutropenia [12 values], diarrhoea [12 values], stomatitis [10 values], fatigue [8 values], alopecia [7 values], hand-foot syndrome [5 values] and skin reaction [5 values]) and 49 of non-specific chemotherapy-related adverse events. In most cases, it was difficult to directly compare the utility values as various definitions and study-specific vignettes were used for the ADEs of interest.
LIMITATIONS: This review was designed to provide an overall description of existing literature reporting utility values for chemotherapy-related ADEs. The findings were not exhaustive and were limited to publications that could be identified using the search strategy employed and those reported in the English language.
CONCLUSIONS: This review identified wide ranges in the utility values reported for broad categories of specific chemotherapy-related ADEs. There were difficulties in comparing the values directly as various study-specific definitions were used for these ADEs and most studies did not make the vignettes used in the valuation exercises available. It is recommended that a basic minimum requirement be developed for the transparent reporting of study designs eliciting utility values, incorporating key criteria such as reporting how the vignettes were developed and presenting the vignettes used in the valuation tasks as well as valuing and reporting the utility values of the ADE-free base states. It is also recommended, in the future, for studies valuing the utilities of chemotherapy-related ADEs to define the ADEs according to the National Cancer Institute (NCI) definitions for chemotherapy-related ADEs as the use of the same definition across studies would ease the comparison and selection of utility values and make the overall inclusion of adverse events within economic models of chemotherapy agents much more straightforward.
METHODS: This observational retrospective study was conducted on files of all solid cancer patients who admitted to a general hospital between 1 January 2003 and 31 December 2006. All data were categorical and analyzed for association with neutropenia.
RESULTS: 117 neutropenic patients were studied, 83 (70.9%) of them suffering from fever ranging between 38.5-39 °C, with hypotension (53; 27.3%) and headache 51 (26.3%) as the most common clinical signs. Only 34 (29.1%) neutropenic patients underwent culture testing and only 14 (41.2%) showed positive growth, gram negative types predominating (9; 64.2%), mainly Escherichia coli (5; 35.7%), with gram positive only in 5 (35.7%). Significant associations were found for fever and clinical signs with neutropenia severity (P<0.05), but not neutropenia onset (P>0.05). Logistic regression results showed strong significant association between presence of fever (P=0.02, OR=1.3) (95% confidence interval (CI)) hypotension and headache (P=0.001, OR=1.148) (95% CI) with neutropenia severity.
CONCLUSION: Fever and clinical signs specifically headache and hypotension are symptoms associated with severe neutropenia in solid cancer patients. Both may primarily result from bacterial infection, particularly gram negative forms.