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Biomarcadors; Neoplàsies colorectals; Mutacions Biomarcadores; Neoplasias colorrectales; Mutaciones Biomarkers; Colorectal neoplasms; Mutations Colorectal cancer (CRC) is a public health problem: it is the third most common cancer in men (746,000 new cases/year) and the second in women (614,000 new cases/year), representing the second leading cause of death by cancer worldwide. The survival of patients with metastatic CRC (mCRC) has increased prominently in recent years, reaching a median of 25 to 30 months. A growing number of patients with mCRC are candidates to receive a treatment in third line or beyond, although the optimal drug regimen and sequence are still unknown. In this situation of refractoriness, there are several alternatives: (1) To administer sequentially the 2 oral drugs approved in this indication: trifluridine/tipiracil and regorafenib, which have shown a statistically significant benefit in progression-free survival and overall survival with a different toxicity profile. (2) To administer cetuximab or panitumumab in treatment-naive patients with RAS wild type, which is increasingly rare because these drugs are usually indicated in first- or second-line. (3) To reuse drugs already administered that were discontinued owing to toxicity or progression (oxaliplatin, irinotecan, fluoropyrimidine, antiangiogenics, anti-epidermal growth factor receptor [if RAS wild-type]). High-quality evidence is limited, but this strategy is often used in routine clinical practice in the absence of alternative therapies especially in patients with good performance status. (4) To use specific treatments for very selected populations, such as trastuzumab/lapatinib in mCRC human epidermal growth factor receptor 2-positive, immunotherapy in microsatellite instability, intrahepatic therapies in limited disease or primarily located in the liver, although the main recommendation is to include patients in clinical trials.

The factors affecting the decisions for the treatment for patients with metastatic colorectal cancer (mCRC) are related to the patient, the tumor, and the treatment itself. Both cetuximab and panitumumab are anti-EGFR monoclonal antibody options for patients with RAS wild-type tumors. Several trials comparing these agents with bevacizumab are analyzed in this paper. The liver is the most common site of metastases in patients with CRC, and perioperative chemotherapy has been shown to yield benefits in this setting. In the second-line treatment for mCRC, maintenance with bevacizumab after progression following first-line treatment is convenient in some groups of patients with mCRC. Also, aflibercept has demonstrated benefits in response rate, progression-free survival, and overall survival in second-line treatment, whereas regorafenib provides benefits to patients progressing on all standard therapies. Several novel therapeutic options for patients with mCRC are under development, and these are discussed.

Axitinib as maintenance therapy versus placebo after first-line chemotherapy has shown statistically significant longer median progression free survival and a tend in overall survival in metastatic colorectal cancer patients. Introduction: The aim of this study was to evaluate the efficacy and safety of maintenance therapy with axitinib versus placebo following induction therapy in patients with metastatic colorectal cancer (mCRC). Patients and Methods: In this double-blinded, phase II trial, patients with mCRC who had not progressed after 6 to 8 months of first-line chemotherapy were randomized to receive axitinib (5 mg twice a day) (arm A) or placebo (arm B). Results: Forty-nine patients were included: 25 in arm A and 24 in arm B. The median follow-up was 26.07 months (95% confidence interval [CI], 18.44-31.73 months). Progression-free survival (PFS) rate at 6 months was 40.00% (95% CI, 21.28%-58.12%) in the axitinib arm versus 8.33% (95% CI, 1.44%-23.30%) in the placebo arm (P =.0141). The median PFS was statistically significantly longer in the axitinib group than in the placebo group (4.96 vs. 3.16 months; hazard ratio, 0.46; 95% CI, 0.25-0.86; P =.0116). Median overall survival was also longer in the axitinib arm but did not reach statistical significance (27.61 vs. 19.99 months; hazard ratio, 0.68; 95% CI, 0.31-1.48; P =.3279). Grade 3 to 4 treatment-related toxicities were experienced by 7 patients (28%) in cohort A and 1 patient (4%) in cohort B (P =.0488). The most frequent grade 3 to 4 treatment-related toxicities were hypertension, diarrhea, and asthenia. There were no toxic deaths. The study was prematurely closed because of slow recruitment. Conclusions: In our study, maintenance treatment with axitinib monotherapy showed a significant increase in PFS and a good safety profile. Axitinib should be further explored as a possible option for first-line chemotherapy maintenance treatment in patients with mCRC. (C) 2018 Elsevier Inc. All rights reserved.

Hand-foot syndrome (HFS) is a limiting toxicity of capecitabine, which is not life-threatening but could compromise capecitabine efficacy.This phase II, multicenter, non-controlled study assessed the safety, particularly grade three HFS incidence, and efficacy of four capecitabine-based chemotherapy regimens [cisplatin/capecitabine (CX), epirubicin/cisplatin/capecitabine (ECX), epirubicin/oxaliplatin/capecitabine (EOX) and docetaxel/cisplatin/capecitabine (DCX)] as first-line treatment for advanced and/or metastatic gastric cancer.One hundred and eight patients were assigned to one of the four treatment groups, according to investigator's criteria, and grouped together for both safety and efficacy primary analyses. HFS was reported in 31 patients (19.6%) and its first presentation occurred at a median of 72 days (range 19-209 days). Grade 3 HFS developed in 6.3, 5.2, 3.7 and 2.4%, of patients receiving ECX, DCX, EOX or CX chemotherapy regimen, respectively. Capecitabine dose reduction/discontinuation due to HFS was required in 5.7% of patients (9/158). The most common (10%) grade 3-4 treatment-related AEs were neutropenia (15.2%), asthenia (12.0%) and diarrhoea (11.4%).A moderate incidence of HFS was reported in patients treated with capecitabine, which generally presented late and required dose reduction in1/3 of patients. The results suggest that capecitabine may be useful in combination with standard fluorouracil-based regimens in patients with advanced and/or metastatic gastric cancer with favourable safety profile.

Aims and background: The addition of bevacizumab to preoperative chemotherapy is a common therapeutic practice in patients with colorectal liver metastases. The aim of the present study was to assess the effect of bevacizumab on postoperative complications after liver resection. Methods:A retrospective analysis was performed including patients who underwent liver resection for colorectal liver metastases after receiving chemotherapy with or without bevacizumab in two hospitals. Univariate logistic regression models were used to identify predictors of postoperative morbidity in both groups of patients. Results: A total of 76 patients were analyzed: 22 patients did not receive preoperative chemotherapy (control group), 21 patients received preoperative chemotherapy alone and 33 patients received preoperative chemotherapy in combination with bevacizumab. The median number of chemotherapy cycles received was 4 (range, 1-23) for the chemotherapy group and 7 (range, 2-36) for the chemotherapy plus bevacizumab group Morbidity rate was similar in the three groups of patients considered: 54.5 %, 47.6% and 39.4, respectively. The most common complications were infections and wound complications. The number of preoperative chemotherapy cycles received was the only clinical variable that was significantly correlated with postoperative comorbidity. Conclusions: Our results support the evidence that the addition of bevacizumab to preoperative chemotherapy does not increase the risk of complications following surgery of colorectal liver metastases.