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.
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This paper describes the database of children with cancer in the EUROCARE study and the methodology used to analyse and report survival. This is the first systematic evaluation of survival after childhood cancer on a large scale in Europe: approximately 45,000 cases were included, diagnosed between 1978 and 1992 (34,814 cases diagnosed in 1978--1989 and an additional set of 9495 cases diagnosed in 1990--1992) and followed-up until 1995. Data were provided from 34 population-based registries (four specialised for childhood cancer registrations and one specialised registry for childhood leukaemia) in 17 countries of Europe (where there was national coverage in 10 countries). ⋯ Age-standardised cumulative survival rates and European averages (weighted and pooled) were also computed. Cox regression models were used to evaluate geographical and temporal differences. The EUROCARE database represents a unique source of information on survival of childhood cancer patients in Europe, intercountry differences and time trends in survival.