Etoposide is an increasingly used and well-tolerated drug in cancer medicine. Its cytotoxic action is phase-specific and it has demonstrated schedule dependency in both in vitro and animal studies, but clinical evidence of the importance of drug scheduling is uncertain. The two administration schedules of etoposide that have been compared in this randomized study of 39 patients with previously untreated extensive small-cell lung cancer treated with single-agent etoposide were 500 mg/m2 as a continuous intravenous (IV) infusion over 24 hours or five consecutive daily 2-hour infusions each of 100 mg/m2. Both regimens were repeated every 3 weeks, for a maximum of six cycles. Patients received combination chemotherapy with vincristine, doxorubicin, and cyclophosphamide (VAC) or radiotherapy on failure to respond or at relapse, depending on their Karnofsky performance status. The same therapy was used in both arms of the study. All patients are evaluable for response to etoposide. In the 24-hour arm, two patients achieved a partial remission, resulting in an overall response rate of 10%. In the 5-day schedule, 16 patients had a partial response and one had a complete remission, producing an overall response rate of 89%, which was significantly superior to that in the 24-hour arm (P less than .001). The median duration of remission to etoposide in the 5-day arm was 4.5 months. Bone marrow toxicity was similar in both schedules. Etoposide pharmacokinetics were measured in all patients, and total areas under the concentration versus time curves (AUCs) were equivalent in both regimens. This study has clearly demonstrated the importance of etoposide scheduling in humans, and the superiority of five daily infusions over a 24-hour continuous infusion. The response rate to single-agent etoposide using an efficacious schedule in extensive small-cell lung cancer has been determined to be in excess of 80%.

Objective: Hepatic steatosis may occur in association with insulin resistance and obesity, two features commonly seen in Cushing's syndrome (CS). The aim of this report is to assess the prevalence of hepatic steatosis in patients with active CS using computed tomography (CT) and to identify any associations between hepatic steatosis, endocrine and biochemical variables and body fat distribution. Patients and measurements: We identified 50 patients with active CS in whom appropriate CT was available to allow measurement of liver and spleen attenuation. In 26 patients, abdominal fat measurements were also available. Serum markers of CS and liver function tests were recorded. Results: Ten of 50 patients had a liver-to-spleen CT attenuation ratio (L/S) of less than 1, indicating hepatic steatosis. There was a significant negative correlation between both liver attenuation and L/S ratio with total abdominal fat area, visceral fat area, the percentage of visceral fat and the visceral to subcutaneous fat ratio; the strongest negative correlation was found between visceral fat area and L/S ratio (r ¼ 2 0.638, P , 0.001, n ¼ 26). L/S ratio positively correlated with alkaline phosphatase levels (r ¼ þ0.423, P ¼ 0.044, n ¼ 23) but with no other serum marker of CS activity or liver enzyme. Conclusions: We have demonstrated hepatic steatosis on CT in 20% of patients with active CS. The presence of hepatic steatosis was significantly correlated with total abdominal fat area and visceral fat area.

Summary The frequency and severity of fatty infiltration of the liver in patients receiving 5-fluorouracil (5-FU) and folinic acid has not been documented systematically. Its development can result in difficulty assessing disease progression, and treatment may be altered inappropriately. Twenty-seven patients with colon cancer and liver metastases receiving 5-FU and folinic acid were studied with computerized tomography (CT) before treatment and after six or 12 cycles of chemotherapy. Forty-seven per cent of patients developed hepatic steatosis during treatment. There was no correlation between development of hepatic steatosis and the dose of chemotherapy or the liver function tests. Hepatic steatosis occurs commonly in patients receiving 5-FU and folinic acid and can be severe. Its development can make hepatic metastases difficult to assess and if its benign nature is not appreciated treatment may be inappropriately altered.Keywords: colon cancer; liver steatosis; computerized tomography; chemotherapy; 5-fluorouracilIn the treatment of patients with advanced colorectal cancer, abdominal computerized tomography (CT) is the most widely used technique to determine stage and to monitor the response of liver metastases and other sites of disease to 5-fluorouracil (5-FU)-based chemotherapy. The diagnosis of metastatic disease is either made during laparotomy or by CT-or ultrasound-guided liver biopsy.It has been observed, while scanning such patients, that they may develop a decrease in liver attenuation consistent with steatosis during treatment with 5-FU, which is used extensively alone or in combination with other drugs for adenocarcinoma of the large bowel. Although fatty change of the liver is well recognized after administration of various chemotherapy regimens (Leevy and Tygstrup, 1976), its frequency and severity has not been documented. Also its occurrence after 5-FU alone or with folinic acid has been noted incidentally in one study and found only to occur when administered with interferon in another (Moertel et al, 1993;Sorensen et al, 1995). The accuracy of CT in establishing the presence of fatty change of the liver is well established (Bydder et al, 1980). The decrease in liver attenuation is important because metastases demonstrated on CT are usually of lower attenuation than normal liver parenchyma and as the liver becomes more fatty, and therefore less dense, the metastases can become increasingly difficult to delineate. This may result in the false impression of a therapeutic response. The confusion can be exacerbated particularly in the presence of focal sparring within fatty change that can mimic metastases (Yates and Streight, 1986). Treatment may be stopped if this benign cause for the liver appearances is misinterpreted as progressive disease.Received 11 August 1997 Revised 24 September 1997 Accepted 11 November 1997 Correspondence to: PD Peppercorn The aim of this study is to examine the frequency and severity of fatty change of the liver as seen on CT in patients receiving 5-FU and folinic...

Objective: Our aims were to describe the abdominal fat distribution in male patients with Cushing's syndrome (CS) on computerised tomography (CT), to compare our findings with non-cushingoid patients, to validate previous reports of increased visceral fat in female patients with CS and to identify any correlations between fat distribution and biochemical findings. Design: Retrospective and observational. Patients: Appropriate CT scans were identified in 31 patients (seven male) with active CS. Measurements: Total, visceral and subcutaneous fat areas were obtained. The percentage of visceral fat and the visceral to subcutaneous fat ratio (V:S ratio) were calculated. Biochemical data were recorded. Control data of fat distribution were obtained from the literature. Results: There was a significant increase in the V:S ratio in male patients with CS when compared with non-cushingoid controls (1.175^0.59 vs 0.77^0.39, 95% confidence interval (CI) 0.0817 -0.728). There was a significant increase in the V:S ratio in female patients with CS (0.845^0.53 vs 0.38^0.19, 95% CI 0.269 -0.661). There was no difference in the V:S ratio between male and female patients with CS (1.175^0.59 vs 0.845^0.53, 95% CI 20.144 -0.804). No significant correlations between fat distribution and glucose levels, circulating cortisol, ACTH or lipids were found. Conclusions: Our data demonstrate an increase in visceral fat distribution in both male and female patients with CS, with the abolition of the normal male to female difference in visceral fat. Increased visceral fat may increase the risk of the metabolic syndrome in this group of patients.

Asymptomatic carotid arterial disease occurs frequently in young patients following neck radiation therapy for Hodgkin lymphoma. No difference in prevalence was shown between only radiation therapy and radiation therapy plus chemotherapy.