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

¹ Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts; ² Department of Health Sciences Research, Mayo Clinic Cancer Center, Rochester, Minnesota; ³ Division of Hematology/Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; ⁴ Cancer Prevention Research Unit, Departments of Medicine and Oncology, Lady Davis Research Institute of Jewish General Hospital and McGill University, Montreal, Quebec, Canada; ⁵ Iowa Oncology Research Association Community Clinical Oncology Program, Des Moines, Iowa; ⁶ Division of Medical Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania; ⁷ Division of Hematology and Oncology, University of Kansas Medical Center, Kansas City, Kansas; and ⁸ National Cancer Institute of Canada, St. Catharines, Ontario, Canada

Requests for reprints: Jeffrey A. Meyerhardt, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115. Phone: 617-632-6855; Fax: 617-632-5370. E-mail: jmeyerhardt{at}partners.org

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.