Phase II study of trifluridine/tipiracil (TAS‑102) therapy in elderly patients with colorectal cancer (T‑CORE1401): geriatric assessment tools and plasma drug concentrations as possible predictive biomarkers

Purpose The current study aimed to determine the efficacy of trifluridine/tipiracil for elderly patients with advanced colorectal cancer. Methods This single-arm, open-label, multicenter, phase II study included elderly patients aged 65 years or more who had fluoropyrimidine-refractory advanced colorectal cancer and received trifluridine/tipiracil (70 mg/m2, days 1–5 and 8–12, every 4 weeks). The primary endpoint was progression-free survival (PFS), while secondary endpoints included overall survival (OS), overall response rate (ORR), toxicities, association between efficacy and geriatric assessment scores, and association between toxicity and plasma drug concentrations. Results A total of 30 patients with a mean age of 73 years were enrolled. Median PFS was 2.3 months (95% confidence interval, 1.9–4.3 months), while median OS was 5.7 months (95% confidence interval, 3.7–8.9 months). Patients had an ORR of 0%, with 57% having stable disease. Grade 4 neutropenia was observed in 13% of the patients. Patients with a higher G8 score (15 or more) showed longer PFS than those with a lower G8 score (median 4.6 vs. 2.0 months; p = 0.047). Moreover, patients with grade 3 or 4 neutropenia showed higher maximum trifluridine concentrations than those with grade 1 or 2 neutropenia (mean 2945 vs. 2107 ng/mL; p = 0.036). Discussion The current phase II trial demonstrated that trifluridine/tipiracil was an effective and well-tolerated option for elderly patients with advanced colorectal cancer. Moreover, geriatric assessment tools and/or plasma drug concentration monitoring might be helpful in predicting the efficacy and toxicities in elderly patients receiving this drug. Trial registration number UMIN000017589, 15/May/2015 (The University Hospital Medical Information Network

Upper arm central venous port implantation: a 6-year single institutional retrospective analysis and pictorial essay of procedures for insertion.

The requirement of central venous (CV) port implantation is increasing with the increase in the number of cancer patients and advancement in chemotherapy. In our division, medical oncologists have implanted all CV ports to save time and consultation costs to other departments. Recently, upper arm implantation has become the first choice as a safe and comfortable method in our unit. Here we report our experience and discuss the procedure and its potential advantages.All CV port implantations (n = 599) performed in our unit from January 2006 to December 2011 were analyzed. Procedural success and complication rates between subclavian and upper arm groups were compared.Both groups had similar patient characteristics. Upper arm CV port and subclavian implantations were equivalently successful and safe. Although we only retrospectively analyzed data from a single center, the upper arm group had a significantly lower overall postprocedural complication rate than the subclavian group. No pneumothorax risk, less risk of arterial puncture by ultrasound, feasibility of stopping potential arterial bleeding, and prevention of accidental arterial cannulation by targeting the characteristic solitary basilic vein were the identified advantages of upper arm CV port implantation. In addition to the aforementioned advantages, there is no risk of "pinch-off syndrome," possibly less patient fear of manipulation, no scars on the neck and chest, easier accessibility, and compatibility with the "peripherally inserted central catheter" technique.Upper arm implantation may benefit clinicians and patients with respect to safety and comfort. We also introduce our methods for upper arm CV port implantation with the videos

Efficacy and safety of denosumab versus zoledronic acid in delaying skeletal-related events in patients with gastrointestinal cancer, pancreas-biliary system cancer, and other rare cancers

Background: Bone is a metastatic site for various types of cancer. Cancer patients in whom bone metastases progress often have skeletal-related events (SREs). Denosumab and zoledronic acid are both bone-modifying agents that prevent the occurrence of SREs. Denosumab has been shown to be superior to zoledronic acid in delaying SREs in various types of cancer, such as breast cancer, lung cancer, and multiple myeloma. However, it is still uncertain whether denosumab is superior to zoledronic acid in delaying the time to SREs in other types of cancers, including gastrointestinal cancer, pancreas-biliary system cancer, and other rare cancers. Patients and methods: This retrospective study was conducted based on medical records from 2009 to 2015. Eligible patients who had been diagnosed with bone metastases from gastrointestinal cancer, pancreas-biliary system cancer, and rare cancers were included. Patients were assigned to a denosumab group, zoledronic acid group, or group without bone-modifying agent treatment (no-treatment group). Results: The study included 168 patients. The times to SREs in the denosumab, zoledronic acid, and no-treatment groups were 186 days [95% confidence interval (CI), 96–323 days], 79 days (95% CI, 45–118 days), and 31 days (95% CI, 13–76 days), respectively. Although, a few patients had grade 3 or 4 adverse events in the denosumab and zoledronic acid groups, the bone-modifying agent treatment was not terminated. Conclusion: From the perspective of the efficacy and safety of denosumab for delaying the time to SREs, denosumab should be used to prevent SREs in patients with bone metastases from gastrointestinal cancer, pancreas-biliary system cancer, and other rare cancers

Images of postprocedural complications that could be prevented with an upper arm CV port.

<p>(<b>A</b>) <b>Catheter pinch-off syndrome and fracture. </b><i>Arrow</i> indicates a “pinched-off” and fractured site of a catheter. <i>Arrowheads</i> indicate the fractured distal catheter fragments that had migrated into the pulmonary artery through the heart. (<b>B</b>) <b>Catheter inversion.</b> Left panel, <i>Arrow</i> indicates a normal catheter placed centrally. Note that there is a sweep turning point at this puncture site that may cause tension derived from an elastic restoring force. Right panel, <i>Arrowheads</i> indicate the peripherally inverted distal portion of a catheter for the same case.</p

Examples of anticipated preoperative difficulties with the procedure confirmed on CT scan images.

<p>(<b>A</b>) <b>SVC syndrome.. </b><i>Arrow</i> indicates the excluded SVC by a tumor. (<b>B</b>) <b>Tortuous collateral blood circulation.. </b><i>Arrows</i> indicate the contrast-enhanced tortuous collateral blood circulation attributable to a modification caused by surgery, radiation, or spontaneous occlusion.</p