A phase II study of recombinant human interleukin-4 for advanced or recurrent non-small cell lung cancer.

PURPOSE: Recombinant human interleukin-4 is a pleiotropic cytokine that has shown antitumor activity in preclinical models and activity in phase I clinical trials. PATIENTS AND METHODS: This was a randomized phase II study testing two doses of recombinant human interleukin-4 (0.25 microgram/kg and 1.0 microgram/kg) administered subcutaneously three times per week in advanced non-small cell lung cancer. RESULTS: Sixty-three patients were enrolled (22 receiving 0.25 microgram/kg and 41 taking 1.0 microgram/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 was IIIb in 11 patients and IV in 52. Forty-four patients had received prior combination chemotherapy, predominantly cisplatin based. Recombinant human interleukin-4 was well tolerated, with no myelosuppression or elevations of liver enzymes, bilirubin, or blood glucose. The most frequent symptoms (any grade) in the 0.25-microgram dose were fatigue (13/22) and fever (8/22). Severe vomiting and dyspnea were observed in one patient each. In the 1.0-microgram dose group, a similar toxicity pattern (any grade) was seen, with fatigue (18/41), fever (14/41), and anorexia (12/41). One patient each had severe hypotension and chest pain. One patient was withdrawn from the study because of a perforated duodenal ulcer. Fifty-five patients were evaluable for response. In the 1.0-microgram group, there was one partial response of > 5.5 years' duration, and eight patients had stable disease of 106 to 350 days' duration. All patients had stage IV disease, and 24 patients had progressed during previous chemotherapy. In the 0.25-microgram group, one patient had stable disease. DISCUSSION: Recombinant human interleukin-4 can be administered safely and may have antitumor activity in non-small cell lung cancer. The higher dose (1.0 microgram/kg) may be associated with a higher incidence of stable disease. In view of the low toxicity seen at both dose levels, a phase II study investigating higher recombinant human interleukin-4 doses is ongoing. Recombinant human interleukin-4 should be explored further, alone or in combination with other cytokines, chemotherapy, or radiotherapy.