Adverse events in the treatment of colorectal cancer: Their use as predictive markers and impact on quality of life

Colorectal cancer (CRC) is a common disease in all western countries. The CRC treatment process has been revolutionised over the past years, and the prognosis of CRC has improved, but we lack information regarding the prognostic and predictive factors that would help us to optimise the therapy for an individual patient. In addition, with improved survival rates, both acute and long-term toxicities require more attention. Hypertension (HTN) is a well-recognised adverse event that is associated with all drugs involved in anti-VEGF (vascular endothelial growth factor) inhibition. The first study discussed in this thesis investigated whether HTN could act as a surrogate marker for efficacy during bevacizumab-containing therapy. According to our results, treatment-associated HTN might predict the outcome of bevacizumab-containing chemotherapy in mCRC patients and could potentially be utilized as a biomarker for continued care. The role of the H. pylori infection as a confounding gastrointestinal comorbidity in the diagnosis of CRC is not well known, and it is not established whether H. pylori infection worsens chemotherapy-induced gastrointestinal toxicity. In the second sub-study, we studied the role of different symptoms and H. pylori for CRC diagnostics. We observed that dyspeptic symptoms and the presence of H. pylori infection at the baseline delayed the initial diagnosis of CRC, but we observed no association between H. pylori infection and gastrointestinal adverse events during 5-FU-based adjuvant chemotherapy. Therefore, the eradication of H. pylori infections before providing 5-FU-based adjuvant chemotherapy cannot be routinely recommended. The association between survival and adverse events in several types of cancer has been established, but data for CRC patients are limited. In the third sub-study, we assessed whether adverse events could predict disease-free survival (DFS) or overall survival (OS) in stage II-III CRC patients. According to our results, adverse events related to treatment with adjuvant 5-FU chemotherapy in early stage CRC patients, especially non-haematological adverse events, are strongly associated with the prediction of improved DFS and OS. Adverse events could guide the clinician in bringing about dose modifications, to maximize the treatment efficacy, while ensuring a lesser level of toxicity. The use of oxaliplatin in the adjuvant setting reduces the risk of death 20% in stage III CRC patients. The major adverse event associated with oxaliplatin-based regimens is peripheral neuropathy, but the prevalence of acute and long-term neuropathy is not well established. It is not well known whether there is a difference in the neuropathy observed with two standard regimens (CAPOX and FOLFOX), and whether long-term neuropathy influences the quality of life (QOL). In the fourth sub-study, we analysed the prevalence of oxaliplatin-induced acute and long-term neuropathy during and after treatment with CAPOX and FOLFOX and studied the effect of long-term neuropathy on QOL in a real-life patient population. According to our results, long-term neuropathy is observed after therapy in a significant proportion of patients, but it does not impair global health status. Long-term neuropathy is not preventable in all patients with a reduction in the duration of therapy, but the performance status might predict the risk of long-term neuropathy.