European journal of cancer : official journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
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In colorectal cancer, leucovorin-modulated 5-fluorouracil (5-FU) has been the mainstay of both adjuvant treatment and treatment of metastatic disease for many years. In advanced disease, response rates of 10-43% are reported; efforts to improve efficacy through schedule modification, including prolonged infusions, have led to limited success. New agents with improved efficacy, tolerability and ease of administration are required. ⋯ Two large, phase III studies of capecitabine in metastatic disease demonstrated objective response rates of 26.6 and 24.8%. UFT/leucovorin has also been evaluated in phase III trials, with an 11.7% response rate reported. Both agents are being evaluated in combination with oxaliplatin and irinotecan, and ultimately oral fluoropyrimidines as monotherapy or combination therapy may replace intravenous (i.v.) 5-FU as first-line treatment for metastatic colorectal cancer.
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Peritoneal seeding from colorectal cancer has a very poor prognosis and is relatively resistant to systemic chemotherapy. We performed a phase I/II trial to investigate the feasibility and effectiveness of extensive cytoreductive surgery in combination with intra-operative hyperthermic intraperitoneal chemotherapy (HIPEC) in these patients. 29 patients with peritoneal carcinomatosis of colorectal origin without evidence of distant metastases underwent cytoreductive surgery and intra-operative HIPEC with mitomycin-C (MMC), followed by systemic chemotherapy with 5-fluorouracil (5-FU)/leucovorin. Surgical complications occurred in 11 patients (38%). ⋯ After a median follow-up of 38 months (range 26-52 months) we found a 2- and 3-year survival rate (Kaplan-Meier) of 45 and 23%, respectively. Extensive cytoreductive surgery and HIPEC is feasible in patients with peritoneal seeding of colorectal cancer. First results suggest that a higher median survival could be achieved compared with conventional palliative surgery and systemic chemotherapy, therefore a randomised phase III study is now being conducted.
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Randomized Controlled Trial Multicenter Study Comparative Study Clinical Trial
Comparison of L-758,298, a prodrug for the selective neurokinin-1 antagonist, L-754,030, with ondansetron for the prevention of cisplatin-induced emesis.
Substance P is localised in brainstem regions associated with emesis. Based on studies in the ferret, it was postulated that a neurokinin-1 (NK1) receptor antagonist would have antiemetic activity as monotherapy in humans receiving chemotherapy. L-758,298 is a water-soluble, intravenous (i.v.) prodrug for L-754,030, a potent and selective NK1 receptor antagonist. ⋯ No serious adverse events were attributed to L-758,298. A single dose of L-758,298 substantially suppressed the delayed nausea and vomiting characteristic of high dose cisplatin and also appeared to reduce acute emesis post-cisplatin. The data also support the proposition that the underlying mechanism(s) of acute and delayed emesis are different.