A PHASE-II PILOT TRIAL OF 13-CIS RETINOIC ACID AND INTERFERON-ALPHA IN PATIENTS WITH ADVANCED PANCREATIC-CARCINOMA

BACKGROUND. Advanced unresectable pancreatic adenocarcinoma has a dism al prognosis. The authors previously have shown that retinoic acid (RA ) and interferon-alpha (IFN-alpha) inhibit growth and induce different iation in human pancreatic carcinoma cells in vitro and in vivo. The p urpose of this trial was to examine the feasibility and tolerability o f a combination therapy of 13-cis RA and IFN-alpha in patients with ad vanced unresectable pancreatic carcinoma. METHODS. Twenty-two patients (median age, 62 years) with histologically confirmed, unresectable pa ncreatic adenocarcinoma classified as International Union Against Canc er Stage III (5 patients) or IV (17 patients) were included. Patients received 1 mg/kg body weight 13-cis RA orally and 6 million IU IFN-alp ha subcutaneously daily. Restaging by ultrasound, computed tomography scan, and chest X-ray was performed every 2 months. RESULTS. No comple te remission and 1 partial remission (PR) (4.5%) were observed. Fourte en patients (63.6%) demonstrated stable disease with a median duration of 5.0 months (range, 2.3-17.7+ months). Toxicity mainly was related to IFN-alpha and predominantly was hematologic (no toxicity was World Health Organization [WHO] Grade 4 and 13.6% were WHO Grade 3). Nonhema tologic toxicities did not exceed Grade 2 (skin and oral mucosa) and m ainly were related to 13-cis RA. The median survival of the patients w ith Stage III disease was 8.7 months (range, 6.8-23.9+ months) and was 7.4 months for patients with Stage TV disease (range, 0.9-19.2+ month s), resulting in a median overall survival of 7.7 months (range, 0.9-2 3.9+ months). CONCLUSIONS. Combination therapy with 13-cis RA and IFN- alpha is feasible and well tolerated in patients with advanced pancrea tic carcinoma. Based on the median survival rates observed in this stu dy this combination should be investigated further in Phase III trials . (C) 1998 American Cancer Society.