A Phase II pilot trial of 13-cis retinoic acid and interferon-α in patients with advanced pancreatic carcinoma

✍ Scribed by Felix H. Brembeck; Klaus Schoppmeyer; Ursula Leupold; Costel Gornistu; Volker Keim; Joachim Mössner; Ernst-Otto Riecken; Stefan Rosewicz

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 87 KB
• Volume: 83
• Category: Article
• ISSN: 0008-543X
• DOI: 10.1002/(sici)1097-0142(19981201)83:11<2317::aid-cncr11>3.0.co;2-p

✦ Synopsis

BACKGROUND.

Advanced unresectable pancreatic adenocarcinoma has a dismal prognosis. The authors previously have shown that retinoic acid (RA) and interferon-␣ (IFN-␣) inhibit growth and induce differentiation in human pancreatic carcinoma cells in vitro and in vivo. The purpose of this trial was to examine the feasibility and tolerability of a combination therapy of 13-cis RA and IFN-␣ in patients with advanced unresectable pancreatic carcinoma.

METHODS.

Twenty-two patients (median age, 62 years) with histologically confirmed, unresectable pancreatic adenocarcinoma classified as International Union Against Cancer 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-␣ subcutaneously daily. Restaging by ultrasound, computed tomography scan, and chest X-ray was performed every 2 months.

RESULTS.

No complete remission and 1 partial remission (PR) (4.5%) were observed. Fourteen patients (63.6%) demonstrated stable disease with a median duration of 5.0 months (range, 2.3-17.7ϩ months). Toxicity mainly was related to IFN-␣ and predominantly was hematologic (no toxicity was World Health Organization [WHO] Grade 4 and 13.6% were WHO Grade 3). Nonhematologic toxicities did not exceed Grade 2 (skin and oral mucosa) and mainly were related to 13-cis RA. The median survival of the patients with Stage III disease was 8.7 months (range, 6.8 -23.9ϩ months) and was 7.4 months for patients with Stage IV disease (range, 0.9 -19.2ϩ months), resulting in a median overall survival of 7.7 months (range, 0.9 -23.9ϩ months).

CONCLUSIONS.

Combination therapy with 13-cis RA and IFN-␣ is feasible and well tolerated in patients with advanced pancreatic carcinoma. Based on the median survival rates observed in this study this combination should be investigated further in Phase III trials.