PHASE-II STUDY OF ALL-TRANS-RETINOIC ACID AND ALPHA-INTERFERON IN PATIENTS WITH ADVANCED NON-SMALL-CELL LUNG-CANCER

Between April 1993 and June 1994, 29 patients (pts) with unresectable, locally advanced, or metastatic non-small cell lung cancer were treat ed with a combination of p.o. trans-retinoic acid (TRA), 150 mg/m(2)/d ay, in three divided doses and s.c. IFN-alpha, 3 x 10(6) units/day, Th e age range was 41-80 years (median, 63 years), The Eastern Cooperativ e Oncology Group performance status was 0-1 (24 pts) and 2 (5 pts), Pt s had advanced disease, refractory to conventional therapy (5 stage II IB and 24 stage IV), Twenty-one pts had adenocarcinoma, six had squamo us cell carcinoma, and two had large cell carcinoma, Only 3 pts comple ted 8 weeks of treatment, requiring neither interruption nor dose modi fication, Fatigue occurred in 88% of pts, A syndrome complex consistin g of dry oral and nasal mucosa, recurrent sinus infections, and epista xis occurred in 64% of pts, Grade II/III dermatitis was seen in 52%, S evere scrotal dermatitis was seen in 7 pts (47% of 15 males), Hypertri glyceridemia was moderate/severe in 11 pts, and 3 pts required gemfibr ozil for levels up to 1660 mg/dl, Hematological toxicity was not encou ntered, and none of the pts had leukocytosis, One pt died with complic ations of myocardial infarction while on TRA/IFN-alpha, Twenty-five pt s had more than 2 weeks of treatment and are evaluable for response; t wo pts died early with complications of cancer, and two pts declined t o continue after only 3 and 5 days of treatment, Final assessment of r esponse was by accepted clinical and radiological criteria at 8 weeks, There have been four objective responses: complete response, 2 (18+ a nd 17 months) and partial response, 2 (7 and 14 months), Responses wer e observed in all histologies, Combined differentiation treatment with TRA/IFN-alpha has modest but objective activity in non-small cell lun g cancer, Toxicity is considerable. Additional studies to elucidate th e biological basis of TRA/IFN-alpha and to define prognostic parameter s predicting response are needed.