International Groups Consult on Prioritizing Chemicals

There is no information on the effect of food or concurrent drug administration on the bioavailability of oral etoposide, despite the fact that treatment is frequently administered over several days and most often in combination with other cytotoxic agents. The influence of these factors has been studied in 11 patients, receiving combination cytotoxic therapy for extensive small cell lung carcinoma. Neither food nor concurrent oral or intravenous chemotherapy had a significant effect on the mean plasma concentrations of etoposide, achieved following oral administration. Wide variation in peak plasma concentrations and in area under the concentration*time curve (AUC) occurred both between and within patients. It appears unnecessary for patients receiving etoposide (at 100mg) to fast prior to drug administration. Furthermore, oral etoposide (at 100mg and at 400mg) may be given in combination with other cytotoxic agents without compromising its bioavailability. Etoposide was introduced into clinical trials in the early 1970s (Issell, 1982) and is established in the treatment of several malignancies, including small cell lung cancer, germ cell tumours and lymphomas The bioavailability of the oral etoposide capsule has been shown to be approximately 50% but with large variation between patients (D'Incalci et al., 1982; Harvey et al., 1984a). Despite the widespread use of oral etoposide over 3-5 days and its predominant use as part of combination chemo-there are no data concerning the influence of food or other chemotherapy on etoposide bioavailability. The intestinal absorption of some drugs has been shown to be affected by both food (Melander, 1978; McLean et al., 1978; Pinkerton et al., 1980) and chemotherapy (Pinkerton et al., 1982). The effect of food and concomitant oral and intravenous chemotherapy on the bioavailability of etoposide has therefore been studied. Patients Eleven patients receiving chemotherapy for extensive small cell lung carcinoma were studied. All were ambulant (performance score > 60% Karnofsky et al., 1948) with normal bone marrow, hepatic and renal function. No patients had disturbance of the gastrointestinal tract. Eight patients receiving primary chemotherapy were studied on 3 separate occasions to assess the effect of food and concomitant oral chemotherapy on etoposide bioavailability (Study 1). Six patients (3 of whom had previously been part of the above study) were receiving therapy for relapsed extensive SCLC and were studied on 3 successive days to assess the effect of intravenous and oral chemo-therapy on etoposide bioavailability (Study 2). Treatment Study 1. The effect of food and oral chemotherapy on etoposide …