Background: Ether lipids could provide new prospects in cancer therapy after successful preclinical investigations. Edelfosine has been the most thoroughly investigated substance in the ether lipid group. So far, no standard therapy has been set up for advanced non-small-cell bronchogenic carcinoma. Therefore, in a phase II study 116 patients with advanced inoperable non-small-cell bronchogenic carcinoma were treated with the alkyl-lysophospholipid edelfosine (EF). Material and Methods: The phenotype modifier EF was initially applied in a daily oral dosage of 300 mg (dissolved in milk) over a period of 4 weeks, then increased to a daily dosage of 900 mg if tolerated well, and continued with the highest tolerable dosage. Therapy was continued until either tumor progression or negative side effects were documented. 35 patients could not be treated for the intended therapy period of at least 8 weeks due to early tumor progression (18 patients), unacceptable gastrointestinal side effects (14 patients), lack of compliance (1 patient), refusal of therapy (1 patient) and change of therapy (1 patient). Results: 81 patients could be evaluated for remission status; of these, 2 showed partial remission, 68 showed ‘no change’, and 11 had unaltered progression of the tumor. Median survival time for these 81 patients was 244 days, for all 116 patients it was 199 days. Retrospectively, in these 81 patients the spontaneous tumor development during the 2 months before EF therapy could be analyzed. Tumor progression during this period could be documented in 1 patient with partial remission, in 46 patients with diagnosis ‘no change’, and in 11 patients with unaltered tumor progression. The survival times of these three groups of patients did not differ significantly. All 116 patients were evaluable for toxicity. Manifestations of gastrointestinal problems were anorexia, nausea, vomiting, diarrhea, obstipation (mostly WHO grades I+Π), but treatment was not required. Toxic effects on organs or late toxicity could not be documented.Conclusions: The high proportion of patients with stationary tumor status was remarkable. Objective tumor remission was extremely rare. On the other hand, the rate of progression was low. This might be explained by the fact that EF is rather a phenotype modifier than a typical cytostatic drug.