Are metformin, statin and aspirin use still associated with overall mortality among colorectal cancer patients with diabetes if adjusted for one another?

BACKGROUND: Metformin, statin and aspirin use seem associated with decreased mortality in cancer patients, though, without adjusting for one another. Independent associations of these drugs with overall mortality after colorectal cancer (CRC) diagnosis within glucose-lowering drugs (GLDs) users were assessed. METHODS: Patients starting GLDs before CRC diagnosis (1998-2011) were selected from the Eindhoven Cancer Registry linked with the PHARMO Database Network. The Cox regression model, with time since CRC diagnosis, included time-dependent variables of cumulative exposure to metformin, statins and aspirin after cancer diagnosis and time-dependent ever-never terms for drug exposure. RESULTS: A total of 1043 patients used GLDs before CRC diagnosis; 666 (64%) used metformin, 639 (61%) used statins and 490 (47%) used aspirin after CRC diagnosis. Multivariable analyses revealed that longer cumulative exposure to metformin was not associated with overall mortality (HRCumulative exposure/6 months 1.02; 95% CI 0.97-1.07), whereas the favourable effect of statins increased with cumulative exposure (HRCumulative exposure/6 months 0.93; 95% CI 0.89-0.98). No association between aspirin use and overall mortality was seen (HRCumulative exposure/6 months 0.98; 95% CI 0.93-1.03). CONCLUSIONS: No independent association between cumulative exposure to metformin, aspirin and overall mortality was found. Cumulative exposure to statins after CRC diagnosis was associated with lower overall mortality, supporting a drug effect of statins among GLDs users.

Diminishing differences in treatment between patients with colorectal cancer with and without diabetes: a population-based study.

AIMS: An increasing number of oncologists will be confronted with individuals having diabetes and cancer. We assessed changes in patient-, tumour- and treatment-related variables in patients with colorectal cancer with and without diabetes. METHODS: All 17 170 cases of primary colorectal cancer between 1995 and 2010 in the South-Eastern Netherlands were included. The Cochrane-Armitage test and logistic regression analysis were used to analyse trends. RESULTS: In total, 11 893 patients were diagnosed with colon cancer and 5277 with rectal cancer, of whom 1711 (14%) and 609 (12%), respectively, had diabetes at the time of cancer diagnosis. Patients with colorectal cancer with diabetes compared with those without were approximately 5 years older and more often diagnosed with proximal colon tumours (60 vs. 54%; P < 0.0001). Chemotherapy administration significantly increased in patients with stage III colon cancer with and without diabetes (from 17% in 1995-1998 to 50% in 2007-2010, 38% to 63%, respectively; P < 0.0001). However, in the most recent period, and after adjusting for the co-variables age, gender, year of diagnosis and specific co-morbidities, patients with stage III colon cancer with diabetes received adjuvant chemotherapy less frequently than those without [odds ratio 0.7 (95% CI 0.5-0.9); P = 0.002]. The proportion of patients with stage II/III rectal cancer with and without diabetes who underwent radiotherapy has been similar in recent years (91 vs. 87%). CONCLUSIONS: Although the administration of chemotherapy and radiotherapy increased between 1995 and 2010 in patients with colorectal cancer with and without diabetes, patients with colorectal cancer with diabetes continue to receive chemotherapy less frequently than those without diabetes.

Changes in glucose-lowering drug use before and after cancer diagnosis in patients with diabetes.

AIM: This study explores the changes in glucose-lowering drug (GLD) use before and after cancer diagnosis among patients with diabetes. METHODS: New GLD users (1998-2011) living in the Dutch ECR-PHARMO catchment area were selected from the PHARMO Database Network (n=52,228). Those with a primary cancer diagnosis were considered cases (n=3281) and matched with eligible controls (n=12,891) without cancer during follow-up. Conditional logistic regression analysis was used to assess changes in GLD use, such as treatment add-ons, treatments drops and initiation of insulin, for cases compared with controls associated with specific cancer types in four time windows (6-3 and 0-3months before cancer diagnosis; 0-3 and 3-6months after cancer diagnosis). RESULTS: In the 3months before cancer diagnosis, patients with upper gastrointestinal (GI) cancers (oesophageal, stomach, pancreatic, liver cancers) had higher odds of initiating insulin (OR: 9.3; 95% CI: 3.6-24.1); to a lesser extent, this was also observed in the 3months prior to that (at 6months, OR: 3.9; 95% CI: 1.3-12.1). Diagnosis of colorectal (OR: 3.4; 95% CI: 1.4-8.4), pulmonary (OR: 2.5; 95% CI: 1.1-5.4) and upper GI (OR: 13.6; 95% CI: 5.0-36.9) cancers was associated with increased odds of initiating insulin in the 3months after cancer diagnosis. During all study time windows, the odds of treatment drops were higher for patients with upper GI cancers whereas, for most other cancers, these odds were higher only after a diagnosis of cancer. CONCLUSION: The greater odds of initiating insulin during the 6months prior to diagnosis of upper GI cancers suggest reverse causation. After cancer diagnosis, drops in use of GLDs was commonly seen.

Colorectal cancer, diabetes and survival: epidemiological insights.

Colorectal cancer (CRC) patients with pre-existing diabetes have significantly lower rates of overall survival compared with patients without diabetes. Against this backdrop, the American Diabetes Association and American Cancer Society in 2010 reviewed the scientific literature concerning diabetes and cancer. One of the key issues identified for further investigation was the need for a better understanding of whether diabetes influences cancer prognosis above and beyond the prognosis conferred by each disease state independently. Whether the worsened survival of CRC patients with diabetes could be explained by less favourable patient-, tumour- and treatment-related characteristics has also been evaluated in numerous recent studies. However, as most studies did not account for all the various potential confounders, such as cancer stage, comorbidities and body mass index (BMI) in their analyses, the current evidence for the association between diabetes and survival in CRC patients remains inconclusive. Nevertheless, based on multiple examples in the literature, the present review demonstrates that diabetes affects the presentation of CRC as well as its treatment and outcome, which may then result in lower overall rates of survival in patients with, compared to those without, diabetes.

The impact of comorbidity on Health-Related Quality of Life among cancer survivors: analyses of data from the PROFILES registry.

PURPOSE: The aim of this study was to assess the difference in explained variance of Health-Related Quality of Life (HRQoL) between comorbidity, sociodemographic characteristics and cancer characteristics. This association was assessed among thyroid cancer, colorectal cancer, and (non-)Hodgkin's lymphoma patients. METHODS: Data from three large population-based surveys on survivors of thyroid cancer, colorectal cancer, and (non-)Hodgkin's lymphoma were used. Cancer-specific HRQoL was assessed with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) of which physical function, emotional function, fatigue, and pain were included in the analyses. Comorbidity was assessed using the Self-reported Comorbidity Questionnaire. The association between comorbidity and HRQoL was assessed with multivariate linear regression models. Semi-partial R (2) was reported to assess the amount of variance in HRQoL explained by comorbidity in comparison with sociodemographic and cancer characteristics. RESULTS: In total, 3,792 cancer survivors were included in this analysis. The variance in HRQoL subscales explained by comorbidity was higher compared with sociodemographic and cancer characteristics for physical function (11-17 vs. 2-4 and 1-2 %, respectively) and emotional function (7-17 vs. 1-3 and 1-3 %, respectively), regardless of cancer type. In addition, comorbidity explained 7-20 and 11-13 % of the variance in pain and fatigue, respectively, compared to 0-4 % for both sociodemographic and cancer characteristics. Osteoarthritis and back pain were strongly associated with physical function and pain, while depression was strongly associated with emotional function. Depression and back pain were strongly associated with fatigue. CONCLUSIONS: This study showed that comorbidity explained more variance in physical and emotional function, pain, and fatigue in comparison with sociodemographic and cancer characteristics in cancer survivors, regardless of cancer type. Our findings emphasize the importance of adjusting for the presence of comorbid diseases when assessing HRQoL in cancer survivors. IMPLICATION FOR CANCER SURVIVORS: Cancer survivors suffering from comorbid diseases experience lower levels of health-related quality of life. Clinicians should become more aware of the impact of comorbidity on HRQoL and provide necessary psychological support to assist self-management of comorbid diseases.