Cachexia is an old disease but a new research area that has recently been vigorously investigated. The diagnostic and staging criteria for cancer-associated cachexia have been established through an ...international consensus report (CR) published in 2011, which may greatly influence the designs and interventions of future clinical trials. However, no standard treatment has been established so far. This may be partially due to the lack of a widely accepted common endpoint for clinical trials. This review aimed to summarize designs and endpoints of 65 randomized controlled trials for cancer cachexia in the past 16 years and seek clinically relevant patient-centered outcomes for future clinical trials. Compared with trials before the CR, trials after the report revealed that the study populations tended to be at the earlier stage of cachexia and included patients with precachexia or those at risk for cachexia. Nonpharmacological interventions have been widely tested, and functional endpoints have increasingly been selected in combination with standard endpoints of body mass or lean body mass. Disability-free survival has recently been used as a functional endpoint in clinical trials in several research fields. It might be also a suitable patient-centered outcome responsive to multiple physical changes in cancer cachexia, and patients might find it more acceptable than other classical endpoints. More efforts would be needed to identify an optimal measurable endpoint and establish a better combination of pharmacological and nonpharmacological interventions to improve the functional prognosis for patients with cancer cachexia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cancer cachexia is a hypercatabolic state associated with malignant tumors and is frequently observed in newly diagnosed advanced lung cancer. 1 A clinically significant decline in physical ...performance is a serious consequence of cancer cachexia, especially in the elderly population 2; however, no existing pharmacological or nonpharmacological interventions can mitigate or prevent this essential outcome. 3 Multimodal interventions, which utilize the synergetic interaction of exercise and nutritional advice with optimal protein supplementation, were shown to enhance the physical performance of athletes and sarcopenic individuals. 4,5 Thus, this combination has been suggested to have potential in the treatment of cancer cachexia. 6 However, while the nutritional advice with oral nutritional supplements was somewhat standardized and shown to increase weight in cancer cachexia, evidence relating to its exercise counterpart is still lacking. 7 The optimal combination of exercise and nutritional intervention has been tested in ongoing trials for patients at high risk for cachexia in advanced cancers. ...this novel agent has the potential to provide an opportunity for the next generation of multimodal interventions, which combine pharmacological and nonpharmacological interventions in cancer cachexia. The most meaningful endpoint of cancer cachexia care might be prolonging active life with satisfying quality of life. 2 However, increasing lean body mass, the standard endpoint in cachexia trials, may not always contribute to an ultimate endpoint, as shown in the anamorelin trials. 3 In addition, each intervention component, including medication, exercise, or nutrition, is insufficient to improve physical function in cancer cachexia when used alone. ...is the time to attempt to enhance the physical performance of patients with cancer cachexia and seek an advance in the quality of their care using a tri-combination strategy.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The efficacy of gefitinib for patients with non‐adenocarcinoma non‐small‐cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations is unclear, because only a small ...percentage of patients enrolled in the clinical trials to evaluate the efficacy of gefitinib for tumors harboring EGFR mutation were non‐adenocarcinoma NSCLC. A pooled analysis was conducted to clarify the efficacy of gefitinib for non‐adenocarcinoma NSCLC patients harboring EGFR mutations. A systematic search of the PUBMED databases was conducted to identify all clinical reports that contained advanced non‐adenocarcinoma NSCLC patients harboring EGFR mutations and treated with gefitinib. The selected patients were advanced non‐adenocarcinoma NSCLC patients harboring EGFR mutations who were treated with gefitinib and described in reports containing the data of the histology, status of EGFR mutations and response to gefitinib. This study selected 33 patients from 15 reports. Twenty‐seven and three of the 33 patients were squamous cell carcinoma and adenosquamous cell carcinoma, respectively. One patient each had large‐cell carcinoma, pleomorphic carcinoma and spindle cell carcinoma. Twenty‐one patients (64%) had sensitive EGFR mutations. The response rate (RR), disease control rate (DCR) and median progression‐free survival (mPFS) was 27%, 67–70% and 3.0 months, respectively. These factors were statistically significantly inferior in the non‐adenocarcinoma NSCLC patients harboring EGFR mutations to adenocarcinoma patients harboring EGFR mutations selected from the same published reports (RR: 27%vs 66%, P = 0.000028; DCR: 67–70%vs 92–93%, P = 0.000014; mPFS: 3.0 vs 9.4 months, P = 0.0001, respectively). Gefitinib is less effective in non‐adenocarcinoma NSCLC harboring EGFR mutations than adenocarcinoma harboring EGFR mutations. (Cancer Sci 2011; 102: 1032–1037)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Cachexia, a disorder associated with anorexia, inflammation, and muscle wasting, is frequent in cancer patients. We performed post‐hoc analyses of the ONO‐7643‐04 study to investigate the ...efficacy and safety of anamorelin in subgroups of Japanese patients with non‐small cell lung cancer (NSCLC).
Methods
The patients were divided into subgroups by baseline characteristics, including sex, age, body mass index, prior weight loss, performance status (PS), concomitant anticancer therapy, and number of previous chemotherapy regimens. The changes from baseline through to 12 weeks for lean body mass (LBM), body weight, and appetite were calculated. Appetite was evaluated using the quality of life questionnaire for cancer patients treated with anticancer drugs (QOL‐ACD) item 8 score. Responder rates were defined as the maintenance/improvement of LBM (≥0 kg), body weight (≥0 kg), or QOL‐ACD item 8 score (≥0) from baseline to all evaluation time points. Safety was evaluated in patients subgrouped by age and PS.
Results
Anamorelin resulted in greater improvements versus placebo in LBM, body weight, and appetite in most subgroups. Anamorelin was also associated with greater LBM, body weight, and appetite responder rates than placebo in nearly all subgroups. Among anamorelin‐treated patients, adverse drug reactions (ADRs) tended to be more frequent with increasing age (<65 years, 19.2%; ≥65 to <75 years, 45.9%; ≥75 years, 60.0%) and PS score (PS 0–1, 38.4%; PS 2, 60.0%). The frequency of serious ADRs was 2.7% and 0% in the PS 0–1 and PS 2 subgroups, respectively.
Conclusion
This study of NSCLC patients with cancer cachexia revealed consistent improvements in LBM, body weight, and appetite across most subgroups of anamorelin‐treated patients. This study also demonstrated the tolerability of anamorelin regardless of age and PS, with a low incidence of serious ADRs in each subgroup.
We performed post‐hoc analyses of the ONO‐7643‐04 study to investigate the efficacy and safety of anamorelin in subgroups of Japanese patients with non‐small cell lung cancer. This study revealed consistent improvements in lean body mass, body weight, and appetite score using QOL‐ACD item 8 across most subgroups of anamorelin‐treated patients versus placebo. This study also demonstrated the tolerability of anamorelin regardless of age and performance status, with a low incidence of serious adverse drug reactions in each subgroup.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Summary
Background
Immune-related hepatotoxicity is often regarded as immune-related hepatitis (irHepatitis) despite including immune-related sclerosing cholangitis (irSC). This study examined the ...clinical differences between irSC and irHepatitis.
Methods
A single-center retrospective study of 530 consecutive patients who received immunotherapy between August 2014 and April 2020 was performed. IrSC and irHepatitis were respectively defined as the radiological presence and absence of bile duct dilation and wall thickness.
Results
Forty-one patients (7.7%) developed immune-related hepatotoxicity. A CT scan was performed on 12 patients, including 11 of 12 with ≥ grade 3 aminotransferase elevations. IrSC and irHepatitis were diagnosed in 4 (0.8%) and 8 (1.5%) patients, respectively. All the irSC patients had been treated with anti-PD-1. IrHepatitis was more common among patients receiving anti-CTLA-4 than among those receiving anti-PD-1/PD-L1 inhibitors (14%, 7/50 vs. 0.2%, 1/480,
P
< 0.001). A ≥ grade 2 alkaline phosphatase (ALP) elevation resulting in a cholestatic pattern was seen in all 4 irSC patients. Among the irSC patients, 3 (3/4, 75%) developed ≥ grade 3 aminotransferases elevation. The median duration from the start of immunotherapy until ≥ grade 2 liver enzymes elevation was 257 and 55.5 days in irSC and irHepatitis patients. The median times for progression from grade 2 to 3 liver enzyme elevation were 17.5 and 0 days, respectively.
Conclusions
IrSC and irHepatitis have different characteristics in the class of immune checkpoint inhibitor and onset pattern. Radiological examination for the diagnosis of irSC should be considered for patients with ≥ grade 2 ALP elevation resulting in a cholestatic pattern. (Registration number J2020-36, Date of registration June 3, 2020)
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Circulating tumor cells (CTCs) are a tumor‐derived material utilized for liquid‐based biopsy; however, capturing rare CTCs for further molecular analysis remains technically challenging, especially ...in non‐small‐cell lung cancer. Here, we report the results of a clinical evaluation of On‐chip Sort, a disposable microfluidic chip‐based cell sorter, for capture and molecular analysis of CTCs from patients with lung adenocarcinoma. Peripheral blood was collected from 30 metastatic lung adenocarcinoma patients to enumerate CTCs using both On‐chip Sort and CellSearch in a blind manner. Captured cells by On‐chip Sort were subjected to further molecular analysis. Peripheral blood samples were also used for detection of EGFR mutations in plasma using droplet digital PCR. Significantly more CTCs were detected by On‐chip Sort (22/30; median 5; range, 0–18 cells/5 mL blood) than by CellSearch (9/30; median, 0; range, 0–12 cells/7.5 mL) (P < 0.01). Thirteen of 30 patients who had a negative CTC count by CellSearch had a positive CTC count by On‐chip Sort. EGFR mutations in CTCs captured by On‐chip Sort were observed in 40.0% (8/20) of patients with EGFR‐mutated primary tumor. EGFR mutations were often observed in 53.3% (8/15) of patients detected in plasma DNA. Expressions of EGFR and vimentin protein on CTCs were also successfully assessed using On‐chip Sort. These results suggest that On‐chip Sort is an efficient method to detect and capture rare CTCs from patients with lung adenocarcinoma that are undetectable with CellSearch. Mutation detection using isolated CTCs remains to be further tackled (UMIN000012488).
CTC analysis by a microfluidic chip cell sorter.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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