Associations between Plasma Insulin-Like Growth Factor Proteins and C-Peptide and Quality of Life in Patients with Metastatic Colorectal Cancer

Abstract

Objective: Predictors of quality of life (QOL) in patients with metastatic colorectal cancer are lacking. The insulin-like growth factor (IGF) family of proteins is associated with QOL in noncancer populations. We sought to study whether these proteins are associated with QOL in patients with colorectal cancer. Method: We used a cohort of 526 patients with metastatic colorectal cancer treated with combination chemotherapy. Plasma samples of IGF-I, IGF-II, IGF binding protein-3, and C-peptide were collected before initiation of chemotherapy. QOL was measured by the uniscale instrument and the Symptom Distress Scale at baseline and throughout treatment. Results: Baseline plasma levels of IGF-I and IGF-II before initiation of chemotherapy were significantly associated with several important baseline QOL measures in patients with metastatic colorectal cancer. Patients with lower levels of IGF-I reported increased distress with regard to appearance, appetite, cough, and nausea intensity after adjustment for potential confounders. Similarly, decreased levels of IGF-II were predictive of worse quality related to appearance, appetite, fatigue, nausea frequency and intensity, pain frequency, and composite Symptom Distress Scale score. IGF binding protein-3 and C-peptide were not predictive of baseline QOL. Baseline biomarkers were not associated with subsequent changes in QOL during treatment. Higher body mass index was significantly associated with superior baseline QOL in several areas; nonetheless, the association of IGF-I and IGF-II with baseline QOL measures remained significant even after controlling for baseline body mass index. Conclusion: Baseline plasma IGF-I and IGF-II are significantly associated with symptom distress. Whether this association is simply reflective of patient nutritional status and/or disease burden or represents an independent biological effect of IGFs on QOL remains uncertain. Nonetheless, these data suggest that molecular biomarkers may be useful predictors of QOL in cancer patients. (Cancer Epidemiol Biomarkers Prev 2005;14(6):1402 -10)

The biology of cancer-related fatigue: a review of the literature

“…Fewer than 10% (4/47) of the articles obtained for this review explored the association of CRF with metabolic and neuroendocrine etiologies (Table 2) [17, 43-45]. Of those four studies, three were cross-sectional [17, 43-44] and one was longitudinal in design [45].…”

“…Of those four studies, three were cross-sectional [17, 43-44] and one was longitudinal in design [45]. A majority of the four studies (3/4; 75%) were recently published (2010-2013), and the predominant cancer population explored was breast cancer (2/4; 50%).…”

Serum IGF-I, IGFBP-3, and matrix metalloproteinase-7 levels and acquired chemo-resistance in advanced colorectal cancer

“…In a previously published report, basal plasma levels of IGF-I and IGF-II, but not IGFBP-3, were associated to greater baseline symptomatology in patients with ACRC. By contrast, IGF-I, IGF-II, and IGFBP-3 were not associated to age, performance status, gender, or overall survival (Meyerhardt et al 2005).…”

The Effects of Obesity and Obesity-Related Conditions on Colorectal Cancer Prognosis

“…Independent of BMI and physical activity, patients with the highest intake of the Western diet had elevated risk of disease-free mortality (HR = 3.25; 95% CI, 2.04-5. 19) and overall mortality (HR = 2.32; 95% CI, 1.36-3.96). When restricted to those with a BMI of 25 kg/m2 or higher, the negative impact of a Western diet was evident among patients with moderate to high intake (60% of the patient population), suggesting that it takes less of a Western-style diet among overweight patients to see an increased risk of recurrence.…”

“…In a clinical trial treating metastatic colorectal cancer patients, higher BMI before initiation of the chemotherapy regimen was predictive of improved perceptions of appearance, bowel function, and appetite. 19 However, the interaction between BMI level, quality of life parameters, and colorectal cancer outcomes was not evaluated. Within another cohort, colorectal cancer patients who were physically active reported better overall quality of life than patients who were inactive.…”