Phase III trial of postoperative cisplatin, interferon alpha-2b, and 5-FU combined with external radiation treatment versus 5-FU alone for patients with resected pancreatic adenocarcinoma – CapRI: study protocol [ISRCTN62866759]

Abstract

After surgical intervention with curative intention in specialised centres the five-year survival of patients with carcinoma of the exocrine pancreas is only 15%. The ESPAC-1 trial showed an increased five-year survival of 21% achieved with adjuvant chemotherapy. Investigators from the Virginia Mason Clinic have reported a 5-year survival rate of 55% in a phase II trial evaluating adjuvant chemotherapy, immunotherapy and external-beam radiation. Design:The CapRI study is an open, controlled, prospective, randomised multi-centre phase III trial. Patients in study arm A will be treated as outpatients with 5-Fluorouracil; Cisplatin and 3 million units Interferon alpha-2b for 5 1/2 weeks combined with external beam radiation. After chemo-radiation the patients receive continuous 5-FU infusions for two more cycles. Patients in study arm B will be treated as outpatients with intravenous bolus injections of folinic acid, followed by intravenous bolus injections of 5-FU given on 5 consecutive days every 28 days for 6 cycles. A total of 110 patients with specimen-proven R0 or R1 resected pancreatic adenocarcinoma will be enrolled. An interim analysis for patient safety reasons will be done one year after start of recruitment. Evaluation of the primary endpoint will be performed two years after the last patients' enrolment. Discussion:The aim of this study is to evaluate the overall survival period attained by chemo-radiotherapy including interferon alpha 2b administration with adjuvant chemotherapy. The influence of interferon alpha on the effectiveness of the patients' chemoradiation regimen, the toxicity, the disease-free interval and the quality of life are analysed. Different factors are tested in terms of their potential role as predictive markers.

Soluble MIC is elevated in the serum of patients with pancreatic carcinoma diminishing γδ T cell cytotoxicity

“…2,22 However, the mechanism by which IFN-a in pancreatic carcinoma mediates its beneficial effect remained unclear. It is well known that the activity of NK cells is regulated by various cytokines, among them IFN-a, 23 and recent studies have implicated IFN-a in the induction of NKG2DL expression, especially on dendritic cells leading to subsequent activation of NK cells.…”

Ex vivo chemosensitivity testing and gene expression profiling predict response towards adjuvant gemcitabine treatment in pancreatic cancer

“…Figure 1A shows the KaplanMeier survival curve of this patient cohort. Seven patients received first-line adjuvant chemotherapy with gemcitabine, two patients were included into the CapRI study (for protocol, see reference Knaebel et al, 2005), one patient received gemcitabine/capecitabine and eight patients received no chemotherapy. Analysis of seven patients treated with first-line gemcitabine revealed a time to relapse of 193 days, as judged by time from initiation of chemotherapy until radiologically detected recurrence of the disease.…”

Synergistic antitumor effect of interferon-ß with gemcitabine in interferon-α-non-responsive pancreatic cancer cells

“…Although the clinical efficacy of IFN-· for pancreatic cancer has been already reported, most of these studies have reported the effect of IFN-·-based combination therapy with other drugs including 5-fluorouracil, cisplatin retinoic acid, or leucovorin (11)(12)(13)(14)(15)(16). Considering that GEM is the golden standard chemotherapeutic agent today, in order to develop more effective combination chemotherapy for pancreatic cancer, we thought it was important to evaluate the antitumor effect of the combination therapy of IFNs and GEM.…”

“…For example, our group has reported the antitumor effect of IFN-· and 5-fluorouracil on hepatocellular carcinoma (HCC) (8)(9)(10), while others have also documented the clinical effect of IFN-· in pancreatic cancer (11)(12)(13)(14)(15). In this regard, a 5-year survival of 55% following IFN-·-based adjuvant chemoradiotherapy for patients with resectable pancreatic cancer it has been reported (16).…”