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Background: Policies of UK clinicians regarding the duration of chemotherapy for patients with advanced colorectal cancer are not consistent. We aimed to compare effectiveness of continuous and intermittent chemotherapy in such patients., Methods: Patients who responded or had stable disease after receiving 12 weeks of the regimens described by de Gramont and Lokich, or raltitrexed chemotherapy, were randomised to either intermittent (a break in chemotherapy, re-starting on the same drug on progression), or continuous chemotherapy until progression., Findings: 354 patients (178 intermittent, 176 continuous) were enrolled from 42 UK centres. At randomisation, 41% of participants had part or complete response; 59% were stable. Only 66 (37%) patients allocated to intermittent treatment restarted as planned, after a median of 130 days. Median time on treatment after restarting was 84 days. Patients in the continuous group remained on treatment for a median of a further 92 days. Similar proportions of patients in both groups received second-line therapy. Patients on intermittent chemotherapy had significantly fewer toxic effects and serious adverse events than those in the continuous group. There was no clear evidence of a difference in overall survival (hazard ratio 0.87 favouring intermittent, 95% CI 0.69-1.09, p=0.23)., Interpretation: Our findings provided no clear evidence of a benefit in continuing therapy indefinitely until disease progression. They showed that it is safe to stop chemotherapy after 12 weeks and re-start the same treatment on progression in patients with chemosensitive advanced colorectal cancer.

Background: This randomised trial compared three chemotherapy regimens in the first-line treatment of advanced colorectal cancer, in terms of their effect on overall and progression-free survival; other endpoints included toxicity, symptom palliation, and quality of life., Methods: 905 patients were randomly assigned the de Gramont regimen (n=303; folinic acid 200 mg/m(2), fluorouracil bolus 400 mg/m(2), and infusion 600 mg/m(2) on days 1 and 2, repeated every 14 days), the Lokich regimen (n=301; protracted venous infusion of fluorouracil 300 mg/m(2) daily), or raltitrexed (n=301; 3 mg/m(2) intravenously every 21 days). Analyses were by intention to treat., Findings: Median follow-up of survivors was 67 weeks. For the de Gramont, Lokich, and raltitrexed groups, respectively, median survival was 294, 302, and 266 days. The hazard ratios for overall survival were 0.88 (95% CI 0.70-1.12, p=0.17) for de Gramont versus Lokich, and 0.99 (0.79-1.25, p=0.94) for de Gramont versus raltitrexed. An increase in treatment-related deaths was seen on raltitrexed (de Gramont one, Lokich two, raltitrexed 18) due to combined gastrointestinal and haematological toxicity. Patients' assessment of quality of life showed that raltitrexed was inferior to the fluorouracil-based regimens, especially in terms of palliation and functioning., Interpretation: The deGramont and Lokich regimens were similar in terms of survival, quality of life, and response rates. The Lokich regimen was associated with more central line complications and hand-foot syndrome. Raltitrexed showed similar response rates and overall survival to the de Gramont regimen and was easier to administer, but resulted in greater toxicity and inferior quality of life.

A prospective study of child health has been continued until the children were 36 months old. The mortality rate in the second year was 8.1%. The most common cause of death was chronic undernutrition. The 79 children suffered seventy-six episodes of faltering weight gain; 47 lost 0.5 kg, and most did not reach their former weight for 5 months. Marasmus complicated eighteen faltering episodes; three were fatal. Of 45 children remaining in Juba to their 36th month none had marasmus, and their health was improved. 15 of 53 children, mean age 2.25 years, showed developmental delay. After 10 months 7 showed continued delay. Hepatitis B seemed to be transmitted to the children from both mothers and other sources. Day-care centres can help chronically undernourished children, and health education should be directed towards the parents' capabilities.

A prospective survey of child health in Juba has been continued till the infants were 12 months old. They were visited monthly or more often if unwell. During the second 6 months of life 6 died; these deaths added to the 9 which occurred in the first 6 months produced an infant mortality rate of 11.8%. Diarrhoea was the whole or a partial cause of 11 of the 15 deaths in the first year. Growth in length by 12 months was satisfactory but the mean weight of the study infants was then at the third centile for healthy girls. Head circumference at 12 months was below normal and poor development was associated with the smaller head circumferences. Supplementary feeding had been started for all babies by the 12th month but only 4 of 127 had been weaned. 30 documented attacks of diarrhoea took place before supplementary feeding was started, suggesting that water given to infants is often contaminated.

A longitudinal survey of child health in Juba was done to secure data on which preventive schemes could be based. 223 pregnant women were identified in a systematic search of a district. 5 infants were stillborn and 10 were born prematurely. The mothers of 5 of the 10 premature infants had had acute malaria at or immediately preceding delivery. 2 of these premature babies later died from causes attributable to prematurity and therefore indirectly to the preventable maternal malaria. The causes of neonatal mortality included tetanus caused by cutting the cord with a blade of grass. Between the 1st and 6th month, 5 infants died of infective enteritis, 1 of bronchopneumonia, and 1 of pyrexia of undetermined origin associated with convulsions. Growth was much impaired by diarrhoea, which caused 85 attacks among 63 babies, and by lower respiratory infections, of which there were 119 among 74 of the babies. Skin and eye infections were also common. Removal of the unerupted canine teeth, believed to cure or prevent illness, caused much distress and some aspiration bronchopneumonia. Health education and improved hygiene and water supplies would greatly reduce the extent of morbidity and mortality.