Optimizing Adjuvant Therapy for Localized Colon Cancer and Treatment Selection in Advanced Colorectal Cancer.

Results from the pivotal IDEA trial, which evaluated 3 versus 6 months of adjuvant oxaliplatin-based chemotherapy, are incorporated into the NCCN Guidelines for Colon Cancer. The guidelines recommend that for patients with low-risk stage III disease, the preferred regimen is CAPEOX for 3 months or FOLFOX for 3 to 6 months. For patients with high-risk stage III disease, the preferred regimen is CAPEOX for 3 to 6 months or FOLFOX for 6 months. In metastatic disease, tumor sidedness should be a consideration when choosing a biologic. For BRAF-mutated disease, several triplets are now recommended options. Importantly, for a subset of patients with metastatic disease, new to the NCCN Guidelines is the incorporation of nivolumab and pembrolizumab as subsequent therapy for those with microsatellite instability-high or mismatch repair-deficient tumors.

Management of Locoregional Rectal Cancer.

The NCCN Guidelines for Rectal Cancer are now more closely aligned with those for colon cancer. A new MRI-based definition of the rectum has been included and the use of MRI in staging has been elevated in importance. There is a new emphasis on neoadjuvant therapy, especially the concurrent use of chemotherapy and radiotherapy. One of the biggest changes is more acceptance of an observational approach-"watch and wait, nonoperative management"-for select patients experiencing a complete clinical response with no evidence of residual disease after neoadjuvant therapy.

Pectin/Kollicoat SR30D isolated films for colonic delivery [I]: a comparison of normal and colitis-induced models to assess the efficiency of microbially triggered drug delivery.

OBJECTIVES: The purpose of the study was to evaluate digestion of pectin/Kollicoat SR30D free films for colonic delivery in vitro and in vivo. METHODS: Free films containing different ratios of pectin to Kollicoat SR30D were prepared by casting/solvent evaporation method. An in-vitro comparison of swelling, degradation and permeability of the free films was carried out in simulated colon fluids containing caecal contents from normal rats with colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) or oxazolone. A comparative in-vivo evaluation of degradation was also conducted in normal and colitis-induced model rats. KEY FINDINGS: The pectin within the mixed films was susceptible to rat colonic bacterial enzymes. The extent of digestion correlated with the amount of pectin present within the film. In vitro, the swelling index, drug permeability and extent of film digestion in simulated colon fluids with caecal contents obtained from normal rats were higher than from TNBS- or oxazolone-induced model rats, whereas in-vivo degradation was similar in the three groups of rats. The pectin/Kollicoat SR30D free films were completely degraded in the colitis-induced rats. CONCLUSIONS: Pectic/Kollicoat SR30D films may be useful as coatings to target delivery of drugs to the colon.

Clinical outcomes of FOLFIRINOX in locally advanced pancreatic cancer: A single center experience.

Systemic chemotherapy or chemoradiotherapy is the initial primary option for patients with locally advanced pancreatic cancer (LAPC). This study analyzed the effect of FOLFIRINOX and assessed the factors influencing conversion to surgical resectability for LAPC.Sixty-four patients with LAPC who received FOLFIRINOX as initial chemotherapy were enrolled retrospectively. Demographic characteristics, tumor status, interval/dosage/cumulative relative dose intensity (cRDI) of FOLFIRINOX, conversion to resection, and clinical outcomes were reviewed and factors associated with conversion to resectability after FOLFIRINOX were analyzed.After administration of FOLFIRINOX (median 9 cycles, 70% of cRDI), the median patient overall survival (OS) was 17.0 months. Fifteen of 64 patients underwent surgery and R0 resection was achieved in 11 patients. During a median follow-up time of 9.4 months after resection, cumulative recurrence rate was 28.5% at 18 months after resection. The estimated median OS was significantly longer for the resected group (>40 months vs 13 months). There were no statistical differences between the resected and non-resected groups in terms of baseline characteristics, tumor status and hematologic adverse effects. The patients who received standard dose of FOLFIRINOX had higher probability of subsequent resection compared with patients who received reduced dose, although cRDIs did not differ between groups.FOLFIRINOX is an active regimen in patients with LAPC, given acceptable resection rates and promising R0 resection rates. Additionally, our data demonstrate it is advantageous for obtaining resectability to administer FOLFIRINOX without dose reduction.