The hard road to data interpretation: 3 or 6 months of adjuvant chemotherapy for patients with stage III colon cancer?

Background: Six months of adjuvant oxaliplatin-based chemotherapy is standard for patients with stage III colon cancer following surgery. However, oxaliplatin is associated with peripheral neurotoxicity which worsens over treatment duration. Consequently, a shorter treatment duration, if equally effective, would be extremely beneficial. A pooled analysis of data for 12 834 stage III colon cancer patients, from six randomised phase III trials of adjuvant therapy, the International Duration Evaluation of Adjuvant chemotherapy study, was carried out and the results presented at the ASCO Annual Meeting 2017. To clarify the potential impact of these results on clinical practice, ESMO decided to sponsor a special session at their 2017 Annual Meeting dedicated to achieving a more meaningful interpretation of the results. Methods: Medical oncologists from Europe, the United States and Asia selected for their involvement in the trials, together with an independent statistician and an independent clinician, were invited to provide their independent interpretations of the results and contribute to a moderated panel discussion. The pooled analysis evaluated the non-inferiority of 3 versus 6 months of adjuvant FOLFOX/CAPOX therapy but not the non-inferiority of 3 months CAPOX versus 6 months FOLFOX therapy. Results: There was strong evidence of an interaction between the choice of regimen (CAPOX or FOLFOX) and duration of treatment. Patients were classified as either 'fighters' or 'fatalists', and 3-month CAPOX was considered standard for patients classified as fatalists even if they had high-risk disease. However, patients classified as 'fighters' would only receive 3 months of CAPOX if they had low-risk disease but would always receive 6 months of CAPOX/FOLFOX if they had T4 disease. The panel was split on whether they would advocate 3 or 6 months CAPOX therapy based on high-risk N2 disease. Conclusions: The main drivers of the duration of treatment were choice of regimen and patient attitude, with risk, based mainly on T4 stage, having less influence.

ESMO Consensus Guidelines for management of patients with colon and rectal cancer. a personalized approach to clinical decision making.

Colorectal cancer (CRC) is the most common tumour type in both sexes combined in Western countries. Although screening programmes including the implementation of faecal occult blood test and colonoscopy might be able to reduce mortality by removing precursor lesions and by making diagnosis at an earlier stage, the burden of disease and mortality is still high. Improvement of diagnostic and treatment options increased staging accuracy, functional outcome for early stages as well as survival. Although high quality surgery is still the mainstay of curative treatment, the management of CRC must be a multi-modal approach performed by an experienced multi-disciplinary expert team. Optimal choice of the individual treatment modality according to disease localization and extent, tumour biology and patient factors is able to maintain quality of life, enables long-term survival and even cure in selected patients by a combination of chemotherapy and surgery. Treatment decisions must be based on the available evidence, which has been the basis for this consensus conference-based guideline delivering a clear proposal for diagnostic and treatment measures in each stage of rectal and colon cancer and the individual clinical situations. This ESMO guideline is recommended to be used as the basis for treatment and management decisions.

A Case Presentation of a Patient with Microsatellite Instability and BRAF Mutant Metastatic Colon Cancer and Bibliography Update.

This is a case of a patient who presented to the emergency department with acute abdominal pain due to bowel obstruction. An extended right hemicolectomy with ileosigmoid anastomosis due to an obstructing mass on the splenic flexure was urgently performed. During operation, liver and peritoneal lesions were detected and samples were also sent for histological analysis. Pathology report was consistent with poorly differentiated mucinous adenocarcinoma with signet ring cells; peritoneal lesions were confirmed histologically as metastatic. Genetic testing revealed the BRAFV600E mutation and mismatch repair deficiency (dMMR). After progressing on 1st line chemotherapy, the patient has a continuing and long-lasting partial response to 2nd line treatment with pembrolizumab.

Treatment of non-small-cell lung cancer with prolonged oral etoposide.

The efficacy and toxicity of chronic administration of oral etoposide was evaluated in 61 patients with inoperable non-small-cell lung cancer (NSCLC). Ten patients received previous chemotherapy, 15 received radiotherapy, and one received both treatments. Twenty-four patients had concurrent cardiac and/or pulmonary impairment, which precluded more intensive treatment. Etoposide was given orally, 100 mg daily for 7 consecutive days and consequently 100 mg every other day for 14 more days in a 28-day schedule. Partial response was observed in 17 patients (28%; 95% confidence interval, 17-39%) and stable disease in 21 (34%). The median duration of response was 6 months (range, 2-34 months). The median survival for responders was 22 months and that of nonresponders was 7 months (p < 0.001). The median survival for all patients was 9 months (range, 1-35 months; 95% confidence interval, 5.69-12.31%). Toxicity was acceptable. Other than alopecia, which was observed in all patients, myelotoxicity was the most common toxicity--particularly leukopenia, which was severe in nine patients. Other less common toxicities included nausea and vomiting, stomatitis, anorexia, and neurotoxicity and were mild. No treatment-related deaths were observed. In conclusion, the regimen was effective and well tolerated with significant survival benefit for the responders. It represents an interesting therapeutic approach, especially in the elderly.