Vistonuridine and 5-FU overdose — Vistonuridine is an orally administered prodrug of uridine, a specific pharmacologic antidote to 5-fluorouracil (5-FU). It is a safe, effective, and potentially life-saving treatment for 5-FU overdose. In a preliminary study, recovery was reported in all 17 cases treated with vistonuridine for 5-FU overexposure, compared to 2 of 13 who did not receive it [5]. (See "Enterotoxicity of chemotherapeutic agents", section on 'Predictive markers'.)
Vistonuridine is not commercially available, but it has received orphan drug designation for treatment of 5-FU overexposure from both the United States Food and Drug Administration (USFDA) and the European Medicines Agency. In the US, it is available from its manufacturer, Wellstat Therapeutics, under an emergency-use Investigational New Drug (IND) waiver.
Adjuvant chemotherapy for pancreatic cancer — The multicenter randomized ESPAC3 trial directly compared six months of adjuvant treatment with either gemcitabine or bolus leucovorin-modulated 5-FU in patients with resected pancreatic ductal adenocarcinoma [6]. In a preliminary report, the median survival was similar in both groups; however, patients assigned to 5-FU/leucovorin had more grade 3 to 4 treatment-related toxicity and more treatment-related hospitalizations. Given this safety profile, gemcitabine is the preferred agent. (See "Adjuvant and neoadjuvant therapy for pancreatic adenocarcinoma", section on 'Gemcitabine versus 5-FU'.)
Lack of benefit for irinotecan after complete resection of colorectal cancer liver metastases — A course of systemic chemotherapy is usually recommended following resection of isolated colorectal cancer liver metastases, although whether this practice increases cure rates remains unproven. A phase III trial demonstrated no benefit from the addition of irinotecan to 5-FU and leucovorin-based chemotherapy after resection of isolated colorectal cancer liver metastases [7]. Thus, postoperative administration of irinotecan-containing chemotherapy should not be considered a standard approach following resection of liver-isolated metastatic colorectal cancer. (See "Management of potentially resectable colorectal cancer liver metastases", section on 'Systemic chemotherapy'.)
Intermittent versus continuous chemotherapy in patients receiving oxaliplatin for metastatic colorectal cancer — For patients receiving oxaliplatin-based regimens (eg, FOLFOX) for treatment of metastatic colorectal cancer, dose-limiting sensory neuropathy can by mitigated by intermittent oxaliplatin-free intervals. Results from the OPTIMOX2 trial suggest that patients may have a worse outcome if courses of oxaliplatin-based chemotherapy are interspersed with entirely chemotherapy-free intervals [8]. Thus, for patients who develop neuropathy while receiving an oxaliplatin-based regimen (or who have received a cumulative oxaliplatin-dose of ≥680 mg/m2), it is reasonable to discontinue oxaliplatin temporarily while maintaining infusional 5-FU and leucovorin. (See "Systemic chemotherapy for metastatic colorectal cancer: Completed clinical trials", section on 'Intermittent versus continuous oxaliplatin'.)
GENERAL ONCOLOGIC ISSUES
Ginger to prevent chemotherapy-induced nausea — Conventional antiemetics are less effective for the prevention of chemotherapy-induced nausea compared to prevention of vomiting. A randomized placebo-controlled trial conducted in patients receiving a variety of chemotherapy regimens concluded that the addition of ginger (0.5 or 1 g twice daily for six days, starting three days prior to the first day of each chemotherapy cycle) to conventional antiemetics significantly aids in reduction of day 1 nausea [9]. (See "Prevention and treatment of chemotherapy-induced nausea and vomiting", section on Ginger and nonpharmacologic therapies.)
الخميس فبراير 11, 2010 3:40 pm
