Effect of cancer cachexia on first-line chemotherapy in patients with advanced pancreatic cancer: a claims database study in Japan.

BACKGROUND: Cancer cachexia is a multifactorial syndrome leading to progressive functional impairment. How cachexia affects the treatment course of chemotherapy in patients with pancreatic cancer has not been well understood. METHODS: This is an exploratory, retrospective, observational cohort study using the Japanese medical claims database from Medical Data Vision Co., Ltd. The study population included patients diagnosed with pancreatic cancer in whom first-line FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel (GnP) was initiated between October 1, 2018, and September 30, 2020. In this study, we defined patients with cancer cachexia as those who had a weight loss of ≥ 5% in the preceding 6 months. The primary outcome was time-to-treatment failure (TTF). The observation period was six months from the initiation of first-line FFX or GnP treatment. RESULTS: A total of 1897 patients (421 patients into the cachexia group; 1476 patients into the non-cachexia group) were analyzed in this study. The median TTF was 121 days (95% confidence interval [CI] 94-146) in the cachexia group and 143 days (95% CI 134-152) in the non-cachexia group. The hazard ratio for TTF of the cachexia versus non-cachexia group was 1.136 (95% CI 0.979-1.319). The median number of doses was two doses fewer in the cachexia group than in the non-cachexia group for both FFX and GnP. CONCLUSION: Cancer cachexia was suggested to be associated with shorter TTF and a reduced number of doses in patients with pancreatic cancer who received first-line FFX or GnP treatment. Clinical Trial Registration clinicaltrials.jp: UMIN000045820.

[The Second Web Questionnaire Survey on Cancer Cachexia Japanese Evidence for Patients Of Cancer Cachexia â ¡ (J-EPOCC â ¡)-Disease Awareness and Issues Related to Cancer Cachexia Among Healthcare Professionals].

In 2019, the Cancer Cachexia Web Questionnaire Survey(J-EPOCC)was conducted among cancer patients, their families and healthcare professionals in Japan, and it showed that the term"cancer cachexia"was highly recognized among health care professionals, whereas the staging and criteria for cancer cachexia defined by European Palliative Care Research Collaborative( EPCRC)was less understood. Also, many healthcare professionals tended to consider the term"cancer cachexia" as the terminal stage of cancer, and most of them lacked the knowledge that cancer cachexia is a disease complication which is potentially developed from the early stage of cancer. Since anamorelin was approved in 2021 for"Cancer cachexia in unresectable advanced or recurrent of non-small cell lung cancer, gastric cancer, pancreatic cancer and colorectal cancer", the treatment environment for cancer cachexia has greatly changed. Thus, the second Web Questionnaire Survey(J-EPOCC Ⅱ) was conducted in June 2022 to investigate changes in the problem awareness of cancer cachexia, especially appetite loss and weight loss, among patients and their families and healthcare professionals1). The results for healthcare professionals showed that the awareness of the staging and criteria has increased among doctors in 2022 compared with 2019, and an increasing number of doctors considered"cancer cachexia"was associated with loss of muscle mass, totally body weight loss, appetite loss and systemic inflammation that may occur in early stages of cancer. On the other hand, awareness of staging and diagnostic criteria for cancer cachexia has not remarkably changed among medical staff since 2019, with levels of awareness varying among those with different job categories. Therefore, in order to achieve early detection and intervention of cancer cachexia, it is necessary to raise the awareness of cancer cachexia among not only doctors but also medical staff by increasing their opportunities to get to know the disease condition, diagnosis, and treatment of cancer cachexia.

[The Second Web Questionnaire Survey on Cancer Cachexia Japanese Evidence for Patients Of Cancer Cachexiaâ ¡ (J-EPOCCâ ¡)-Challenges in Early Detection and Early Intervention for Appetite Loss and Weight Loss During Cancer Treatment].

In 2019, the Cancer Cachexia Web Questionnaire Survey(J-EPOCC), conducted among cancer patients, their families and healthcare professionals in Japan showed that nearly half of patients who had experienced appetite loss or weight loss during cancer treatment had not consulted with healthcare professionals about their symptoms, and it meant that patients missed the opportunity to receive medical intervention. Since anamorelin was approved in 2021 fo"r Cancer cachexia in non- small cell lung cancer, gastric cancer, pancreatic cancer and colorectal cancer", the treatment environment for cancer cachexia has greatly changed. Thus, the second Web Questionnaire Survey(J-EPOCCⅡ)was conducted in June 2022 to investigate changes in the problem awareness of cancer cachexia, especially appetite loss and weight loss, among patients and their family and healthcare professionals. The results showed that there was no apparent change in awareness of appetite loss and weight loss, suggesting many patients may miss treatment opportunities. Further disease awareness is required among patients and their families to enhance the understanding of the significance of therapeutic interventions for appetite loss or weight loss, and to call their attention for early detection and treatment.

A retrospective cohort study to investigate the incidence of cancer-related weight loss during chemotherapy in gastric cancer patients.

PURPOSE: This study aimed to evaluate cancer-related weight loss (WL) after the start of first-line chemotherapy as a surrogate marker for cancer cachexia in patients with advanced gastric cancer. We investigated the incidence of WL and the relationship between WL and overall survival (OS) or adverse events. METHODS: We conducted a retrospective cohort study in 131 patients with advanced gastric cancer who received first-line systemic chemotherapy between September 1, 2010, and August 31, 2016, at Kurume University Hospital and Shizuoka Cancer Center Hospital. WL was defined in this study as weight loss of > 5% or weight loss of > 2% with a body mass index of < 20 kg/m2 within the last 6 months after the start of chemotherapy. RESULTS: Median age and median Eastern Cooperative Oncology Group performance status of the patients participating in this study were 68 years old and 0, respectively. Incidence of WL was 53% at the first 12 weeks after starting first-line chemotherapy, and increased to 88% after 48 weeks. Overall survival rates were significantly associated with WL at 12, 24, and 48 weeks. Appetite loss and fatigue were more frequent and more severe in patients with WL. CONCLUSION: WL was especially observed in more than half the patients within 12 weeks after starting chemotherapy. WL appeared to relate to adverse events or reduced survival. These results suggest the importance of monitoring WL or providing nutritional support at the beginning of chemotherapy.

Incidence and frequency of cancer cachexia during chemotherapy for advanced pancreatic ductal adenocarcinoma.

PURPOSE: Cachexia influences the patient's physical wellbeing and quality of life, and the patient's ability to tolerate their cancer therapies, especially cytotoxic chemotherapy. The purpose of this study was to investigate the frequency and timing of onset of cancer cachexia during chemotherapy and its association with prognosis and toxicity in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: We performed a retrospective study in patients who underwent first-line chemotherapy after diagnosis of advanced PDAC between 6 June 2008 and 31 March 2017. Base cachexia (weight loss up to 6 months before starting first-line chemotherapy) and follow-up cachexia (after starting first-line chemotherapy) were defined as weight loss > 2% with a body mass index (BMI) < 20 kg/m2 or weight loss > 5%. RESULTS: A total of 150 patients were registered. The median age and BMI were 65 years and 21.7 kg/m2, respectively. Base cachexia occurred in 50% of patients. Follow-up cachexia occurred in 32% within 12 weeks of starting first-line chemotherapy, reaching 64% at 1 year. Overall survival was not significantly different between patients with and without follow-up cachexia, regardless of whether cancer cachexia occurred within 12, 24, or 48 weeks of starting first-line treatment. Appetite loss, fatigue, nausea, and diarrhea were more frequent in patients with follow-up cachexia than in those without follow-up cachexia. CONCLUSION: Follow-up cachexia had an early onset, but was not a prognostic factor for overall survival in patients with PDAC. Some adverse events tended to be more frequent in patients with follow-up cachexia than in those without follow-up cachexia.

[Web Questionnaire Survey on Appetite Loss and Weight Loss Associated with Cancer Cachexia Japanese Evidence for Patients Of Cancer Cachexia(J-EPOCC)-The Understanding of Cancer Cachexia].

Cancer cachexia is multifactor syndrome that occurs in 50-80% of cancer patients and accounts for 20% of cancer deaths. We conducted a web questionnaire survey for healthcare professionals(doctors and medical staff), patients and families to clarify the understanding of cancer cachexia. As a result, it was revealed that the understanding of cancer cachexia among patients and families was low. Cancer cachexia was widely recognized by healthcare professionals, but 3 stages of EPCRC was not. Many of healthcare professionals recalled the image of terminal stage of cancer from the term "cancer cachexia", and they lack awareness that cancer cachexia was a disease complication which developed from the early stage of cancer. Furthermore, there were many doctors who were faced with the problem such as a lack of treatment options for cancer cachexia. From these facts, it is necessary to disseminate scientific concept of cancer cachexia and establish standard of care from the early stage.

[Web Questionnaire Survey on Appetite Loss and Weight Loss Associated with Cancer Cachexia Japanese Evidence for Patients Of Cancer Cachexia(J-EPOCC)-The Problem Awareness of Appetite Loss and Weight Loss].

Appetite loss and weight loss associated with cancer have negative effects on the quality of life and OS of cancer patients. We conducted a web questionnaire survey for healthcare professionals(doctors and medical staff), patients and families to clarify the problem awareness for appetite loss and weight loss associated with cancer. As a result, it turned out that families were more concerned about patients' appetite loss and weight loss, and nearly half of patients haven't consulted their symptoms to healthcare professionals, and it meant that patients missed the opportunity to receive medical intervention due to no consultation. While healthcare professionals have a strong desire to provide dedicated treatment for appetite loss and weight loss in cancer patients, the proportion of patients and families who replied their symptom had improved with the intervention was low. In the near future, it will be necessary to enlighten the importance of symptom management to patients and families and pay attention to their symptom change for healthcare professionals.

A Retrospective Cohort Study to Investigate the Incidence of Cachexia During Chemotherapy in Patients with Colorectal Cancer.

INTRODUCTION: This retrospective study focused on cancer cachexia in clinical practice. We evaluated the incidence of cancer cachexia and the relationship between cancer cachexia and overall survival (OS) or toxicities in patients with advanced colorectal cancer after undergoing first-line systemic chemotherapy. METHODS: We examined 150 patients with colorectal cancer who underwent first-line systemic chemotherapy between February 1, 2010 and August 31, 2016 at Shizuoka Cancer Center Hospital and Kurume University Hospital. Cancer cachexia was defined as > 5% weight loss or > 2% weight loss with a body mass index of < 20 kg/m2 within the past 6 months according to the European Palliative Care Research Collaborative criteria. RESULTS: One hundred patients from Shizuoka Cancer Center and 50 from Kurume University Hospital were registered. Median age and body mass index were 65 years (range 29-85) and 21.7 kg/m2 (14.8-32.5), respectively. Cumulative incidence of cancer cachexia was 50.7% at 24 weeks, and reached 91.3% over the whole study period. OS was significantly different between patients with and without cancer cachexia within 24 weeks after starting first-line treatment, although the onset of cancer cachexia within 24 weeks could not be considered as an independent prognostic factor for OS. Severe appetite loss and fatigue tended to occur more frequently in patients with cancer cachexia within 24 weeks. CONCLUSION: Cancer cachexia appears to have an onset in approximately half of patients with advanced colorectal cancer within 24 weeks after starting first-line treatment. Although causal relationships were controversial, the onset of cancer cachexia within 24 weeks tends to be related to worse outcomes. Thus, it would be better to monitor weight loss leading to cachexia in patients with advanced colorectal cancer, especially within 24 weeks after starting first-line chemotherapy. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN000035002).

The effect of continuous arterial infusion of gabexate mesilate (FOY-007) on experimental acute pancreatitis.

The effectiveness of continuous arterial infusion of Gabexate Mesilate (FOY-007) on experimental acute pancreatitis was investigated. Acute necrotizing pancreatitis was induced by an injection of 10% Na-taurocholate (1ml/kg) into the main pancreatic duct of mongrel dogs. Animals were divided into three groups; Group A: non-treated control, Group B: after the induction of pancreatitis, injected with FOY-007 intravenously (5mg/kg/hr), Group C: after the induction of pancreatitis, injected with FOY-007 via the celiac artery. The changes in the values of amylase and lipase in serum and ascites etc. were examined. A histological examination was done and the FOY-007 concentration of the pancreas was measured. In both groups B and C, the serum levels of amylase and lipase reached significantly to low levels compared with those in group A. The extents of pancreatic parenchyma necrosis in each group were 36.1, 25.3 and 19.5%, respectively, and were significantly improved in group C. In addition, the FOY-007 levels in pancreas specimens in the intraarterial infusion group exceeded those in the intravenous infusion group by 32 times. The results suggest that continuous FOY-007 arterial infusion therapy is useful as a local treatment for severe acute pancreatitis.