Multicenter safety study of mFOLFOX6 for unresectable advanced/recurrent colorectal cancer in elderly patients

<p>Abstract</p> <p>Background</p> <p>Combination chemotherapy with oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX) has become a standard regimen for colorectal cancer. An increase of adverse events with combination chemotherapy is predicted in elderly patients, and it remains controversial whether they should receive the same chemotherapy as younger patients. Accordingly, this study of modified FOLFOX6 (mFOLFOX6) therapy was performed to compare its safety between elderly and non-elderly patients.</p> <p>Methods</p> <p>We prospectively studies 14 non-elderly patients aged <70 years old and 8 elderly patients aged ≥ 70 years with unresectable advanced/recurrent colorectal cancer who received mFOLFOX6 therapy during the period from March 2006 to March 2007. Adverse events and the response to treatment were compared between the elderly and non-elderly groups.</p> <p>Results</p> <p>The main adverse events were neutropenia and peripheral neuropathy, which occurred in 62.5% (≥ grade 3) and 87.5% (≥ grade 1) of elderly patients. The grade and frequency of adverse events were similar in the elderly and non-elderly groups. In some patients with neutropenia, treatment could be continued without reducing the dose of oxaliplatin by deleting bolus 5-fluorouracil. A correlation was found between the cumulative dose of oxaliplatin and the severity of neuropathy, and there were 2 elderly and 3 younger patients in whom discontinuation of treatment was necessary due to peripheral neuropathy. The median number of treatment cycles was 10.0 and 9.5 in the non-elderly and elderly groups, respectively. The response rate was 60.0% in the non-elderly and 50.0% in the elderly group, while the disease control rate was 100% and 83.3% respectively, showing no age-related difference.</p> <p>Conclusion</p> <p>mFOLFOX6 therapy was well-tolerated and effective in both non-elderly and elderly patients. However, discontinuation of treatment was sometimes necessary due to peripheral neuropathy, which is dose-limiting toxicity of this therapy.</p

Epidemiology and natural history of central venous access device use and infusion pump function in the NO16966 trial

Background: Central venous access devices in fluoropyrimidine therapy are associated with complications; however, reliable data are lacking regarding their natural history, associated complications and infusion pump performance in patients with metastatic colorectal cancer.&lt;p&gt;&lt;/p&gt; Methods: We assessed device placement, use during treatment, associated clinical outcomes and infusion pump perfomance in the NO16966 trial.&lt;p&gt;&lt;/p&gt; Results: Device replacement was more common with FOLFOX-4 (5-fluorouracil (5-FU)+oxaliplatin) than XELOX (capecitabine+oxaliplatin) (14.1% vs 5.1%). Baseline device-associated events and post-baseline removal-/placement-related events occurred more frequently with FOLFOX-4 than XELOX (11.5% vs 2.4% and 8.5% vs 2.1%). Pump malfunctions, primarily infusion accelerations in 16% of patients, occurred within 1.6–4.3% of cycles. Fluoropyrimidine-associated grade 3/4 toxicity was increased in FOLFOX-4-treated patients experiencing a malfunction compared with those who did not (97 out of 155 vs 452 out of 825 patients), predominantly with increased grade 3/4 neutropenia (53.5% vs 39.8%). Febrile neutropenia rates were comparable between patient cohorts±malfunction. Efficacy outcomes were similar in patient cohorts±malfunction.&lt;p&gt;&lt;/p&gt; Conclusions: Central venous access device removal or replacement was common and more frequent in patients receiving FOLFOX-4. Pump malfunctions were also common and were associated with increased rates of grade 3/4 haematological adverse events. Oral fluoropyrimidine-based regimens may be preferable to infusional 5-FU based on these findings

Phase II study of S-1 plus leucovorin in patients with metastatic colorectal cancer

Background: S-1, a novel oral fluoropyrimidine, is well tolerated in patients with metastatic colorectal cancer (mCRC). The response rate of S-1 for colorectal cancer is high, ranging from 35% to 40%. This study aimed to evaluate the safety and efficacy of S-1 combined with oral leucovorin (LV) to enhance antitumor activity in chemotherapy-naive patients with mCRC

Laparoscopic extraperitoneal rectal cancer surgery: the clinical practice guidelines of the European Association for Endoscopic Surgery (EAES)

BACKGROUND: The laparoscopic approach is increasingly applied in colorectal surgery. Although laparoscopic surgery in colon cancer has been proved to be safe and feasible with equivalent long-term oncological outcome compared to open surgery, safety and long-term oncological outcome of laparoscopic surgery for rectal cancer remain controversial. Laparoscopic rectal cancer surgery might be efficacious, but indications and limitations are not clearly defined. Therefore, the European Association for Endoscopic Surgery (EAES) has developed this clinical practice guideline. METHODS: An international expert panel was invited to appraise the current literature and to develop evidence-based recommendations. The expert panel constituted for a consensus development conference in May 2010. Thereafter, the recommendations were presented at the annual congress of the EAES in Geneva in June 2010 in a plenary session. A second consensus process (Delphi process) of the recommendations with the explanatory text was necessary due to the changes after the consensus conference. RESULTS: Laparoscopic surgery for extraperitoneal (mid- and low-) rectal cancer is feasible and widely accepted. The laparoscopic approach must offer the same quality of surgical specimen as in open surgery. Short-term outcomes such as bowel function, surgical-site infections, pain and hospital stay are slightly improved with the laparoscopic approach. Laparoscopic resection of rectal cancer is not inferior to the open in terms of disease-free survival, overall survival or local recurrence. Laparoscopic pelvic dissection may impair genitourinary and sexual function after rectal resection, like in open surgery. CONCLUSIONS: Laparoscopic surgery for mid- and low-rectal cancer can be recommended under optimal conditions. Still, most level 1 evidence is for colon cancer surgery rather than rectal cancer. Upcoming results from large randomised trials are awaited to strengthen the evidence for improved short-term results and equal long-term results in comparison with the open approach.</p