EUROSCAN, a randomized trial of vitamin A and N-acetylcysteine in patientswith head and neck cancer or lung cancer

Background: Preclinical evidence suggests that retinoids and antioxidants m ay prevent or delay the occurrence of cancer in the upper or lower airways, but such effects have not been reliably established in clinical studies, T o assess the chemopreventive effects of vitamin A (retinyl palmitate) and N -acetylcysteine, we conducted a large randomized intervention study in pati ents with head and neck cancer or with lung cancer, most of whom had a hist ory of smoking, Methods: From June 1988 through July 1994, a total of 2592 patients (60% with head and neck cancer and 40% with lung cancer) were rand omly assigned to receive 1) retinyl palmitate (300 000 IU daily for 1 year followed by 150 000 IU for a 2(nd) year), 2) N-acetylcysteine (600 mg daily for 2 years), 3) both compounds, or 4) no intervention, All statistical te sts were two-sided. Results: Of the patients, 93.5% had smoked tobacco at s ometime in their lives (and 25% continued to smoke after cancer diagnosis). After a median follow-up of 49 months, 916 patients were reported with an event (recurrence, second primary tumor, or death). No statistically signif icant difference was observed in overall survival or event-free survival be tween patients who received retinyl palmitate and patients who did not. Sim ilarly, no difference was seen in overall survival or event-free survival b etween patients who received N-acetylcysteine and patients who did not. The re was a lower incidence of second primary tumors in the no intervention ar m, but the difference was not statistically significant. Conclusion: A 2 ye ar supplementation of retinyl palmitate and/or N-acetylcysteine resulted in no benefit - in terms of survival, event-free survival, or second primary tumors - for patients with head and neck cancer or with lung cancer, most o f whom were previous or current smokers.