In this double-blind study, the efficacy and safety of a single intravenous dose of a novel antiemetic, granisetron, was assessed at two dose levels (40 micrograms/kg and 160 micrograms/kg). A group of 355 patients were given prophylactic granisetron prior to receiving high-dose cisplatin chemotherapy. In the first 24 h, 57% and 59% of patients, respectively, experienced no vomiting and no more than mild nausea. Two further doses of granisetron (40 micrograms/kg) were permitted in the first 24 h to treat any emergent symptoms of nausea and vomiting; 66 patients (39%) in the 40-micrograms/kg treatment group and 56 patients (34%) in the 160-micrograms/kg group received at least one additional dose. Additional treatment with granisetron resulted in resolution or improvement of symptoms in at least 73% of these patients. Over the 7-day study period, 52% of patients in the lower-dose group and 48% in the higher required no further conventional antiemetic therapy. The two different dose levels were equal both in terms in efficacy and safety. Granisetron was well tolerated throughout the dose range of the study [40-240 micrograms kg-1 (24 h)-1]. The commonest adverse event was headache, seen in 14%-16% of patients. In all but one case this resolved spontaneously or responded to simple treatment.

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This was a multicentre, randomised, double-blind, parallel-group study which included female breast cancer patients, receiving their first of 6 scheduled courses of chemotherapy (cyclophosphamide ≥ 500 mg/m²). Patients received an intravenous dose of 16mg dexa-methasone with either 8 mg ondansetron or 60 mg metoclopramide before chemotherapy, followed by oral dosing with 8 mg ondansetron or 20 mg metoclopramide 3 times daily for 5 days. A total of 93 patients were treated with ondansetron and 94 patients with metoclopramide. On day 1 of their first course of treatment 91 and 60% of patients in the ondansetron and metoclopramide groups respectively were free of emesis (p < 0.001). Over the 5-day treatment period, the corresponding figures were 81 and 48% (p < 0.001). The results for nausea also revealed highly statistically significant treatment differences (p < 0.001) in favour of ondansetron for both day 1 and day 1-5 analyses of the first treatment course. Over the series of courses, 67% of patients receiving ondansetron completed all 6 courses with a maximum of 2 emetic episodes on their worst day, compared with 28% of patients receiving metoclopramide (p < 0.001). A similar analysis for nausea revealed that 49% of patients receiving ondansetron completed all 6 courses with ‘none’ or ‘mild’ nausea compared with 27% of patients receiving metoclopramide (p < 0.001). These differences were reflected in quality of life data (Rotterdam Symptom Checklist). After the first course of treatment, a statistically significant improvement (p = 0.002) in the psychological subscale scores was observed after ondansetron compared with metoclopramide. No differences were observed in the physical or functional activity subscales after the first course. However, the quality of life results over the series of courses revealed a more pronounced difference in favour of ondansetron in the psychological subscale scores (p < 0.001) as well as trends in favour of ondansetron in the physical (p = 0.096) and functional activity (p = 0.056) subscales. Extrapyramidal symptoms were reported in 19 % of patients in the metoclopramide group and resulted in 15 % of patients withdrawing from their randomised anti-emetic schedule, either during or between treatment courses. Other adverse events were generally minor in nature and did not necessitate withdrawal from treatment. In conclusion, this study shows that ondansetron is significantly superior to metoclopramide (each with a single pre-treatment dose of dexamethasone) in the control of emesis over 6 courses of chemotherapy for breast cancer. Importantly, patients given ondansetron had a superior quality of life compared with those given metoclopramide.

A dose of 1000 mg/m(2) bd of capecitabine is recommended for use on an intermittent schedule in combination with these doses and schedule of epirubicin and cisplatin. This regimen is tolerable and active in oesophago-gastric adenocarcinoma. A randomised phase III comparison with ECF is justified.

SUMMARY The effects of cytotoxic therapy on the structure and function of the proximal jejunum were studied in six patients receiving intravenous cyclophosphamide (300 mg/M2), methotrexate (40 mg/M2), and 5-fluorouracil (600 mg/M2) as adjuvant therapy for breast cancer. Using a steady state, triple lumen tube perfusion system the absorption of water and electrolytes was measured before and 48 h after administration of the cytotoxic agents. Jejunal biopsies were obtained at each perfusion. Median (range) water absorption fell from 126 (40-142) to 84 (46-142) ml/h/30 cm, with parallel changes for electrolytes; none of the changes was significant. Brush border disaccharidases did not change at 48 h after chemotherapy, while mature enterocytes appeared normal by both light and electron microscopy. Crypt cells and immature enterocytes, however, showed focal vacuolation by light microscopy, corresponding to the occurrence of large residual bodies (secondary lysosomes) containing partially degraded fragments of damaged crypt cells. The confinement of ultrastructural changes to the immature cell population may explain the failure of this study to show a consistent change in the absorptive function of the jejunum 48 h after chemotherapy.Cytotoxic therapy can cause structural and functional changes in the human proximal intestine. '-3 This effect may be important in the development of gastrointestinal symptoms such as diarrhoea and may lead to malabsorption of orally administered drugs, including cytotoxic agents.4 5 Smith et a!6 could find no change in xylose absorption and faecal fat estimation in patients with biopsy proved depression of crypt cell mitosis, but most previous studies of cytotoxic damage have examined changes of gastrointestinal function and structure independently.The technique of small intestinal perfusion is a sensitive method for detecting changes in the transport of water and electrolytes across the jejunal mucosa and might therefore show relatively minor abnormalities of enterocyte function more readily than conventional intestinal absorption tests.7 We have used small intestinal perfusion to investigate IPresent address:

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