Current controversies in the management of metastatic colorectal cancer.

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.

Role of Kras status in patients with metastatic colorectal cancer receiving first-line chemotherapy plus bevacizumab: a TTD group cooperative study.

BACKGROUND: In the MACRO study, patients with metastatic colorectal cancer (mCRC) were randomised to first-line treatment with 6 cycles of capecitabine and oxaliplatin (XELOX) plus bevacizumab followed by either single-agent bevacizumab or XELOX plus bevacizumab until disease progression. An additional retrospective analysis was performed to define the prognostic value of tumour KRAS status on progression-free survival (PFS), overall survival (OS) and response rates. METHODOLOGY/PRINCIPAL FINDINGS: KRAS data (tumour KRAS status and type of mutation) were collected by questionnaire from participating centres that performed KRAS analyses. These data were then cross-referenced with efficacy data for relevant patients in the MACRO study database. KRAS status was analysed in 394 of the 480 patients (82.1%) in the MACRO study. Wild-type (WT) KRAS tumours were found in 219 patients (56%) and mutant (MT) KRAS in 175 patients (44%). Median PFS was 10.9 months for patients with WT KRAS and 9.4 months for patients with MT KRAS tumours (p=0.0038; HR: 1.40; 95% CI:1.12-1.77). The difference in OS was also significant: 26.7 months versus 18.0 months for WT versus MT KRAS, respectively (p=0.0002; HR: 1.55; 95% CI: 1.23-1.96). Univariate and multivariate analyses showed that KRAS was an independent variable for both PFS and OS. Responses were observed in 126 patients (57.5%) with WT KRAS tumours and 76 patients (43.4%) with MT KRAS tumours (p=0.0054; OR: 1.77; 95% CI: 1.18-2.64). CONCLUSIONS/SIGNIFICANCE: This analysis of the MACRO study suggests a prognostic role for tumour KRAS status in patients with mCRC treated with XELOX plus bevacizumab. For both PFS and OS, KRAS status was an independent factor in univariate and multivariate analyses.

Incidence of hand-foot syndrome with capecitabine in combination with chemotherapy as first-line treatment in patients with advanced and/or metastatic gastric cancer suitable for treatment with a fluoropyrimidine-based regimen.

INTRODUCTION: Hand-foot syndrome (HFS) is a limiting toxicity of capecitabine, which is not life-threatening but could compromise capecitabine efficacy. MATERIALS AND METHODS: 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. RESULTS: 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%). CONCLUSIONS: A moderate incidence of HFS was reported in patients treated with capecitabine, which generally presented late and required dose reduction in < 1/3 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.

Autoevaluación de una vía clínica para mejora del proceso quirúrgico carcinoma de recto / Self-evaluation of a clinical pathway to improve the results of rectal cancer

Objetivo Analizar si la autoevaluación de una vía clínica mejora los resultados del tratamiento del cáncer de recto (CR).Pacientes y método Pacientes intervenidos de CR divididos en 3 grupos según modificaciones bianuales de una vía clínica analizando diversos indicadores. Resultados Ciento sesenta y seis pacientes: grupo A: 2002–2003, n=50; B: 2004–2005, n=53 y C: 2006–2007, n=63; sin diferencias en edad, sexo o comorbilidad. El estudio preoperatorio mejoró con la introducción de TC toracoabdominopélvico: un 76% en el grupo C frente a un 6% del A (p<0,001). Todos los tumores del grupo C fueron estadificados mediante RM, ECO rectal o ambas, frente a un 84% del A (p<0,001). La tasa de amputaciones de recto pasó del 42% en el grupo A, al 17% en el C (p=0,007). Un 48% de cirujanos del grupo A frente al 94% en el C (p<0,001) tenían dedicación específica a la coloproctología. La media de adenopatías analizadas fue: grupo A: 6,2±4,5 frente a 13±6,5 en el C (p<0,001) y se informó del margen circunferencial en un 24% del grupo A frente al 76% en el C (p<0,001). Parámetros como la transfusión perioperatoria de hemoderivados, ingreso en UCI, uso de sonda nasogástrica, tolerancia precoz o analgesia epidural también mejoraron progresivamente. La mortalidad operatoria descendió de forma no significativa hasta el 4,7% y las dehiscencias anastomóticas del 24% al 9,5%, reduciéndose la estancia postoperatoria de 15–11 días (p=0,029).Conclusiones Se han mejorado múltiples indicadores de forma significativa en un período relativamente corto al efectuar autoevaluaciones del proceso (AU)

Objectives To analyse whether the self-evaluation of a clinical pathway improves the results of rectal cancer (RC) treatment. Patients and method Patients operated on for RC were divided into 3 groups according to biannual modifications of a clinical pathway analysing several indicators.Results166 patients: Group A: 2002–3 n=50, B: 2004–5 n=53 and C: 2006–7 n=63, without any differences in age, gender or comorbidity. Preoperative study improved with the introduction of CT scan: 76% in Group C vs. 6% in Group A (P<0.001). All Group C tumours were staged using MR, rectal ultrasound or both, compared to 84% in Group A (P<0.001). The rate of abdominal-perineal resections was reduced from 42% (Group A) to 17% (Group C); (P=0.007) and about 48% of surgeons in Group A vs. 94% in the C had a specific activity in coloproctology (P<0.001). The average lymph node count was: Group A=6.2±4.5 vs. 13±6.5 in the C and circumferential margin analysis was reported in 24% of Group A vs. 76% in Group C (P<0.001). Parameters such as perioperative blood transfusion, ICU admission, use of nasogastric tube, early feeding or epidural analgesia also improved progressively. Operative mortality decreased non-significantly to 4.7% and anastomotic leaks from 24% to 9.5% with a reduction in postoperative stay from 15 to 11 days during the period analysed (P=0.029).Conclusions Several indicators have significantly improved in a relatively short period of time due to self-evaluations of the process (AU)

[Self-evaluation of a clinical pathway to improve the results of rectal cancer]. / Autoevaluación de una vía clínica para mejora del proceso quirúrgico carcinoma de recto.

OBJECTIVES: To analyse whether the self-evaluation of a clinical pathway improves the results of rectal cancer (RC) treatment. PATIENTS AND METHOD: Patients operated on for RC were divided into 3 groups according to biannual modifications of a clinical pathway analysing several indicators. RESULTS: 166 patients: Group A: 2002-3 n=50, B: 2004-5 n=53 and C: 2006-7 n=63, without any differences in age, gender or comorbidity. Preoperative study improved with the introduction of CT scan: 76% in Group C vs. 6% in Group A (P<0.001). All Group C tumours were staged using MR, rectal ultrasound or both, compared to 84% in Group A (P<0.001). The rate of abdominal-perineal resections was reduced from 42% (Group A) to 17% (Group C); (P=0.007) and about 48% of surgeons in Group A vs. 94% in the C had a specific activity in coloproctology (P<0.001). The average lymph node count was: Group A=6.2+/-4.5 vs. 13+/-6.5 in the C and circumferential margin analysis was reported in 24% of Group A vs. 76% in Group C (P<0.001). Parameters such as perioperative blood transfusion, ICU admission, use of nasogastric tube, early feeding or epidural analgesia also improved progressively. Operative mortality decreased non-significantly to 4.7% and anastomotic leaks from 24% to 9.5% with a reduction in postoperative stay from 15 to 11 days during the period analysed (P=0.029). CONCLUSIONS: Several indicators have significantly improved in a relatively short period of time due to self-evaluations of the process.