A PHASE-II STUDY OF RECOMBINANT HUMAN INTERLEUKIN-4 FOR ADVANCED OR RECURRENT NONSMALL CELL LUNG-CANCER

PURPOSE Recombinant human interleukin-4 is a pleiotropic cytokine that has shown antitumor activity in preclinical models and activity in ph ase I clinical trials, PATIENTS AND METHODS This was a randomized phas e II study testing two doses of recombinant human interleukin-4 (0.25 mu g/kg and 1.0 mu g/kg) administered subcutaneously three times per w eek in advanced non-small cell lung cancer, RESULTS Sixty-three patien ts were enrolled (22 receiving 0.25 mu g/kg and 41 taking 1.0 mu g/kg) ; the median age was 61 years, Tumor histology included adenocarcinoma (41 patients), squamous cell carcinoma (12 patients), and other types (10 patients), The initial stage of disease ease was IIIb in 11 patie nts and IV in 52, Forty-four patients had received prior combination c hemotherapy, predominantly cisplatin based, Recombinant human interleu kin-4 was well tolerated, with no myelosuppression or elevations of li ver enzymes, bilirubin, or blood glucose. The most frequent symptoms ( any grade) in the 0.25-mu g dose group were fatigue (13/22) and fever (8/22), Severe vomiting and dyspnea were observed in one patient each, In the 1.0-mu g dose group, a similar toxicity pattern (any grade) wa s seen, with fatigue (18/41), Fever (14/41), and anorexia (12/41), One patient each had severe hypotension and chest pain, One patient was w ithdrawn from the study because of a perforated duodenal ulcer, Fifty- five patients were valuable for response, In the 1.0-mu g group, there was one partial response of 5.5 years' duration, and eight patients h ad stable disease of 106 to 350 days' duration, All patients had stage IV disease, and 24 patients had progressed during precious chemothera py. Hn the 0.25-mu g group, one patient had stable disease, DISCUSSION Recombinant human interleukin-4 can be administered safely and may ha ve antitumor activity in non-small cell lung cancer, The higher dose ( 1.0 mu g/kg) may be associated with a higher incidence of stable disea se, In view of the low toxicity seen at both dose levels, a phase ZI s tudy investigating higher recombinant human interleukin-4 doses is ong oing, Recombinant human interleukin-4 should be explored further, alon e or in combination with other cytokines, chemotherapy, or radiotherap y.