Oral chemotherapeutic regimens with limited toxicity are desirable in that quality of life can be maintained and clinic/hospital visits minimised during therapy. We have investigated the use of extended courses of oral cyclophosphamide and oral etoposide for the treatment of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). A 14-day course of oral combination chemotherapy every 28 days resulted in a 12% response rate and a median survival of 6 months (1-year survival, 26%) in stage IV NSCLC. This regimen could not be intensified with carboplatin because of synergistic granulocytopenia. A 14-day course every 28 days resulted in a 40% response rate and a median survival of 7 months in poor-prognosis extensive-disease SCLC. Pharmacodynamic modelling revealed that the granulocyte nadir could be predicted from a single plasma etoposide level drawn on the second day of therapy, potentially allowing dose adjustment during the treatment cycle. Oral chemotherapy remains a promising route for the treatment of lung cancer.