Management of Chemotherapy- Induced Adverse Effects in the Treatment of Colorectal Cancer

Abstract

The anticancer agents fluorouracil, raltitrexed, irinotecan and oxaliplatin show limited efficacy in the treatment of colorectal cancer and may be associated with substantial toxicity. Therefore, the prevention and reduction of chemotherapy-induced adverse effects is of major significance, in accordance with the increasing concern for the quality of life of patients with cancer. Therapeutic drug monitoring of fluorouracil and chronomodulation of fluorouracil and oxaliplatin, have been effective in reducing the incidence and gravity of adverse effects in several clinical trials. However, these concepts have not been implemented in clinical practice yet. At the present time, dose adaptation and supportive measures are the main tools for toxicity control in the treatment of colorectal cancer. In this review, supportive measures for alleviation of the adverse effects of fluorouracil, raltitrexed, irinotecan and oxaliplatin, respectively, are described, based on study results. The main adverse effects of these agents are myelosuppression, oral mucositis, diarrhoea, acute cholinergic syndrome, nausea and emesis, neurotoxicity, hand-foot syndrome and other cutaneous adverse effects, ocular toxicity, cardiotoxicity, small bowel toxicity, asthenia, elevated liver transaminase levels and alopecia. The incidence and gravity of these adverse effects are more or less related to the agent and administration schedule involved. The supportive measures and recommendations include the use of specific drugs, alterations of administration schedule and several nonpharmacological methods. In addition, guidelines for dosage adjustments when toxicity occurs are presented. For optimal management of adverse effects, patients should be considered individually, while patients, nurses and physicians should cooperate to identify and treat adverse effects in an early stage of their development.

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer

“…Both 5-FU and CPT-11, currently used for this indication, are known to trigger digestive problems [50]. In the present study, the addition of Dbait displayed no local toxicity and induced no digestive problems, suggesting that it could be added to chemotherapy without causing any additional toxicity.…”

“…We have already demonstrated that Dbait administration does not increase the sensitivity of healthy tissues to irradiation in mice [50]. A phase I trial to evaluate the tolerance to local Dbait administration in association with radiotherapy in in-transit metastases of melanoma is currently underway (DNA therapeutics, data on file).…”

Cancer chemotherapy-induced diarrhoea and constipation: mechanisms of damage and prevention strategies

“…Octreotide is another potential drug that may reduce CID [14,25,33,34,57,60]. It works by acting on the epithelial cells, inhibiting gut hormones such as serotonin, vasoactive intestinal peptide and gastrin, as well as increasing intestinal transit time, promoting absorption of electrolytes through the intestine and decreasing mesenteric blood flow, secretion of fluids and electrolytes [34,57,77].…”

“…It works by acting on the epithelial cells, inhibiting gut hormones such as serotonin, vasoactive intestinal peptide and gastrin, as well as increasing intestinal transit time, promoting absorption of electrolytes through the intestine and decreasing mesenteric blood flow, secretion of fluids and electrolytes [34,57,77]. There are a number of clinical trials which have shown that octreotide is effective in decreasing CID [14,25,33,34,57]. Recent clinical guidelines recommend that octreotide is administered at a dose of at least 100 mg subcutaneously twice a day [57] or upward titration of the octreotide dose until the symptoms of diarrhoea are controlled [5].…”

A pilot clinical trial assessing the efficacy and safety of supplementation with a B complex vitamin to reduce the incidence of chemotherapy induced peripheral neuropathy in patients diagnosed with a malignancy

“…The oedema, which is an adverse outcome of chemotherapy administration [368] made it difficult to obtain an accurate sural nerve assessment.…”