Brembeck F H, Schoppmeyer K, Leupold U, Gornistu C, Keim V, Mössner J, Riecken E O, Rosewicz S
Klinikum Benjamin Franklin, Free University of Berlin, Department of Gastroenterology, Germany.
Cancer. 1998 Dec 1;83(11):2317-23. doi: 10.1002/(sici)1097-0142(19981201)83:11<2317::aid-cncr11>3.0.co;2-p.
Advanced unresectable pancreatic adenocarcinoma has a dismal prognosis. The authors previously have shown that retinoic acid (RA) and interferon-alpha (IFN-alpha) 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-alpha in patients with advanced unresectable pancreatic carcinoma.
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-alpha subcutaneously daily. Restaging by ultrasound, computed tomography scan, and chest X-ray was performed every 2 months.
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, 2.3-17.7+ 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). 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, 6.8-23.9+ months) and was 7.4 months for patients with Stage IV disease (range, 0.9-19.2+ months), resulting in a median overall survival of 7.7 months (range, 0.9-23.9+ months).
Combination therapy with 13-cis RA and IFN-alpha 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.
晚期不可切除的胰腺腺癌预后不佳。作者之前已经表明，视黄酸（RA）和α干扰素（IFN-α）在体外和体内均可抑制人胰腺癌细胞的生长并诱导其分化。本试验的目的是研究13-顺式RA与IFN-α联合治疗晚期不可切除胰腺癌患者的可行性和耐受性。
纳入22例经组织学确诊为不可切除的胰腺腺癌患者（中位年龄62岁），国际抗癌联盟分期为III期（5例）或IV期（17例）。患者每天口服1 mg/kg体重的13-顺式RA，并皮下注射600万国际单位的IFN-α。每2个月通过超声、计算机断层扫描和胸部X线进行重新分期。
未观察到完全缓解，仅1例部分缓解（PR）（4.5%）。14例患者（63.6%）病情稳定，中位持续时间为5.0个月（范围2.3 - 17.7 +个月）。毒性主要与IFN-α相关，主要为血液学毒性（无世界卫生组织[WHO] 4级毒性，13.6%为WHO 3级）。非血液学毒性未超过2级（皮肤和口腔黏膜），主要与13-顺式RA相关。III期疾病患者的中位生存期为8.7个月（范围6.8 - 23.9 +个月），IV期疾病患者为7.4个月（范围0.9 - 19.2 +个月），总体中位生存期为7.7个月（范围0.9 - 23.9 +个月）。
13-顺式RA与IFN-α联合治疗晚期胰腺癌患者是可行的，耐受性良好。基于本研究观察到的中位生存率，该联合治疗应在III期试验中进一步研究。
