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Traditionally, the efficacy of cancer treatment in patients with advance or metastatic disease in clinical studies has been studied using overall survival and more recently tumor-based end points such as progression-free survival, measurements of response to treatment. However, these seem not to be the relevant clinical end points in current situation if such end points were no validated as surrogate of overall survival to demonstrate the clinical efficacy. Appropriate, meaningful, primary patient-oriented and patient-reported end points that adequately measure the effects of new therapeutic interventions are then crucial for the advancement of clinical research in metastatic colorectal cancer to complement the results of tumor-based end points. Health-related quality of life (HRQoL) is effectively an evaluation of quality of life and its relationship with health over time. HRQoL includes the patient report at least of the way a disease or its treatment affects its physical, emotional and social well-being. Over the past few years, several phase III trials in a variety of solid cancers have assessed the incremental value of HRQoL in addition to the traditional end points of tumor response and survival results. HRQoL could provide not only complementary clinical data to the primary outcomes, but also more precise predictive and prognostic value. This end point is useful for both clinicians and patients in order to achieve the dogma of precision medicine. The present article examines the use of HRQoL in phase III metastatic colorectal cancer clinical trials, outlines the importance of HRQoL assessment methods, analysis, and results presentation. Moreover, it discusses the relevance of including HRQoL as a primary/co-primary end point to support the progression-free survival results and to assess efficacy of treatment in the advanced disease setting., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Colorectal cancer (CRC) is one of the most common malignancies in Western countries. Over the last 20 years, and the last decade in particular, the clinical outcome for patients with metastatic CRC (mCRC) has improved greatly due not only to an increase in the number of patients being referred for and undergoing surgical resection of their localised metastatic disease but also to a more strategic approach to the delivery of systemic therapy and an expansion in the use of ablative techniques. This reflects the increase in the number of patients that are being managed within a multidisciplinary team environment and specialist cancer centres, and the emergence over the same time period not only of improved imaging techniques but also prognostic and predictive molecular markers. Treatment decisions for patients with mCRC must be evidence-based. Thus, these ESMO consensus guidelines have been developed based on the current available evidence to provide a series of evidence-based recommendations to assist in the treatment and management of patients with mCRC in this rapidly evolving treatment setting., (© The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Identification of predicting factors for anthracyclines-based chemotherapy remains a clinical challenge. Glutathione S-transferase (GSTs) enzymes detoxify chemotherapy drugs and their metabolites. Several polymorphisms in GST genes result in reduced or no activity of the enzymes. Specifically, GSTM1 and GSTT1 genes are polymorphically deleted, the polymorphism GSTP1 c.313A>G (rs1695) determines the amino acid substitution Ile105Val, where the Val-containing enzyme has reduced activity. Also, GSTA1*B allele has reduced levels of GSTA1 enzyme. Several polymorphisms in GSTs have been associated with differences in survival for cancer patients treated with chemotherapy., Patients and Methods: We genotyped a total of five polymorphisms in GSTM1, GSTT1, GSTP1 and GSTA1 genes in 159 patients with locally advanced breast cancer, treated with single-agent doxorubicin or docetaxel (Taxotere). Gene expression microarrays were performed in 67 breast tumor samples. We correlate this data with treatment outcome., Results: In multivariate analysis, patients homozygous GG for GSTP1 c.313A>G SNP had a lower risk of chemoresistance when treated with doxorubicin (odds ratio 0.106; confidence interval 0.012-0.898; P=0.040). No association was found in the docetaxel arm. Also, we found that GSTP1 expression varied significantly among breast cancer molecular subtypes., Conclusions: GSTP1 may constitute another tool contributing to individualized anthracycline-based therapy.

This article summarizes the expert discussion on the management of hepatocellular carcinoma (HCC), which took place during the 10th World Gastrointestinal Cancer Congress (WGICC) in Barcelona, June 2008. A multidisciplinary approach to a patient with HCC is essential, to guarantee optimal diagnosis and staging, planning of surgical options and selection of embolisation strategies or systemic therapies. In many patients, the underlying cirrhosis represents a challenge and determines therapeutic options. There is now robust evidence in favour of systemic therapy with sorafenib in patients with advanced HCC with preserved liver function. Those involved in the care for patients with HCC should be encouraged to participate in well-designed clinical trials, to increase evidence-based knowledge and to make further progress.

Knowledge of the biology and management of rectal cancer continues to improve. A multidisciplinary approach to a patient with rectal cancer by an experienced expert team is mandatory, to assure optimal diagnosis and staging, surgery, selection of the appropriate neo-adjuvant and adjuvant strategy and chemotherapeutic management. Moreover, optimal symptom management also requires a dedicated team of health care professionals. The introduction of total mesorectal excision has been associated with a decrease in the rate of local failure after surgery. High quality surgery and the achievement of pathological measures of quality are a prerequisite to adequate locoregional control. There are now randomized data in favour of chemoradiotherapy or short course radiotherapy in the preoperative setting. Preoperative chemoradiotherapy is more beneficial and has less toxicity for patients with resectable rectal cancer than postoperative chemoradiotherapy. Furthermore chemoradiotherapy leads also to downsizing of locally advanced rectal cancer. New strategies that decrease the likelihood of distant metastases after initial treatment need be developed with high priority. Those involved in the care for patients with rectal cancer should be encouraged to participate in well-designed clinical trials, to increase the evidence-based knowledge and to make further progress. Health care workers involved in the care of rectal cancer patients should be encouraged to adopt quality control processes leading to increased expertise.

Background: The purpose of this study was to determine the relative efficacy of doxorubicin versus methotrexate in combination with intravenous cyclophosphamide and 5-fluorouracil (FAC versus CMF) as adjuvant chemotherapy for operable breast cancer., Patients and Methods: Over a 4-year period, 985 women undergoing curative surgery for breast cancer (T1-3 N0-2 M0, stage I-IIIA, UICC) from nine hospitals were stratified with respect to axillary node involvement (node positive versus node negative) and randomized to receive either FAC (500/50/500/m(2)) every 3 weeks for six cycles or CMF (600/60/600/m(2)) every 3 weeks for six cycles., Results: The relative dose intensities of FAC and CMF were 87% and 85% of planned doses, respectively. Unadjusted data indicated a non-significant trend towards better results with FAC. In the prospectively formed subset of node-negative patients, disease-free survival and overall survival were statistically superior in the FAC treatment arm (P = 0.041 and 0.034, respectively), but this advantage was not seen in the subset of node-positive patients, probably because of a difference in the percentage of patients with four or more positive nodes. Adjusting data for size of treatment effect and potential interactions (number of positive nodes, tumor size, treatment center), the overall relative risk (RR) of disease recurrence and death were significantly lower with FAC treatment (RR 1.2, P = 0.03, and RR 1.3, P = 0.05, respectively). This result was mainly due to the difference observed in the node-negative patient population. Toxicity was mild: FAC induced more alopecia, emesis, mucositis and cardiotoxicity; this last was of clinical concern, but was infrequent and manageable. CMF induced more conjunctivitis and weight gain. There were no toxic deaths., Conclusions: Doxorubicin in combination with day 1 i.v. cyclophosphamide and 5-fluorouracil is superior to methotrexate in combination with day 1 i.v. cyclophosphamide and 5-fluorouracil as adjuvant chemotherapy for operable breast cancer. A treatment effect is particularly evident in the node-negative patients. Although the clinical toxicity of FAC is greater than that of CMF, the levels were manageable and clinically acceptable.

Purpose: To evaluate the anti-tumour activity and tolerance of the combination of paclitaxel plus vinorelbine in metastatic breast cancer (MBC) patients previously treated with anthracyclines., Patients and Methods: Fifty-six MBC patients who have had at least one previous anthracycline-containing chemotherapy regimen were enrolled in this phase II trial. Patients received paclitaxel (135 mg/m2 over one-hour infusion) and vinorelbine (30 mg/m2) both on day 1 of each three-week course of therapy (maximum eight courses or until disease progression was evident)., Results: Six complete and nineteen partial responses were observed among the fifty-four assessable patients (response rate of 46%, 95% CI: 33%-60%). Responses were observed in all disease sites and in all subsets of patients. The response rates when paclitaxel plus vinorelbine were used as first, second and third-line chemotherapy for metastases were 67%, 41% and 35%, respectively. The response rate among anthracycline-refractory patients was 46% (6 of 13). Median time to progression in the overall patient group was 28 weeks. The main toxicities (CTC grade 2 or more) were alopecia, myelosuppression and peripheral neuropathy (85%, 46% and 19% of patients, respectively). Nine patients (17%) had neutropenic fever in fifteen of the three hundred twenty-eight courses administered (5%)., Conclusions: The combination of paclitaxel and vinorelbine on day 1 every three weeks is active in MBC patients with prior anthracycline exposure. The regimen is safe, well tolerated and convenient for the patients.

Background: Oxaliplatin (L-OHP) is a platinum complex that possesses activity against human and murine cells in vitro and in vivo, including colorectal carcinoma-derived cell lines, and cells that have been selected for resistance to cisplatin. We report two consecutive phase II trials of L-OHP for treatment of patients with advanced colorectal carcinoma., Patients and Methods: Fifty-eight patients were entered in study I, and 51 patients in study II. All of the patients had tumor progression when they were treated, prior to their enrollment, with a fluoropyrimidine-containing regimen. In both trials treatment consisted of L-OHP, 130 mg/m2, by i.v. infusion for two hours; the treatment was repeated every 21 days., Results: Response to therapy: Study I: Fifty-five patients were assessed for response. The response rate was 11% (95% CI, 0.03-0.19). Study II: All 51 patients were assessed for response. The response rate was 10% (95% CI, 0.017-0.18). The overall response rate for the 106 evaluated patients was 10% (95% CI, 0.046-0.16). Times to disease progression in responders were 4, 4, 4.5+, 5, 5, 6, 6, 6, 6+, 9, and 13 months. The dose-limiting toxic effect was sensory peripheral neuropathy. The incidence of severe peripheral neuropathy grades was: Study I: grade 3, 23% of patients, and grade 4, 8% of patients. Severe neuropathy had a favorable course in all of the patients who had long-term neurologic follow-up. Diarrhea and myeloid impairment were minor., Conclusion: L-OHP produced modest, but definite antitumor activity in patients with advanced colorectal carcinoma who were previously resistant to chemotherapy including fluoropyrimidines. Toxicity is within acceptable limits of tolerance at the dose and schedule of oxaliplatin used in this trial.