A Phase II Study of Fixed-Dose Rate Gemcitabine Plus Low-Dose Cisplatin Followed by Consolidative Chemoradiation for Locally Advanced Pancreatic Cancer

      Purpose: The optimal strategy for treating locally advanced pancreatic cancer remains controversial, including the respective roles and timing of chemotherapy and radiation. We conducted a Phase II nonrandomized trial to evaluate sequential chemotherapy followed by chemoradiation in this patient population.
      Methods and Materials: Chemotherapy naive patients with locally advanced pancreatic adenocarcinoma were treated with fixed-dose rate gemcitabine (1,000 mg/m2 at 10 mg/m2/min) plus cisplatin 20 mg/m2 on Days 1 and 15 of a 28-day cycle. Those without evidence of extrapancreatic metastases after six cycles of chemotherapy received radiation (5,040 cGy over 28 fractions) with concurrent capecitabine (800 mg/m2 orally twice daily on the day of radiation) as a radiosensitizer.
      Results: A total of 25 patients were enrolled with a median follow-up time of 656 days. Twelve patients (48%) successfully received all six cycles of chemotherapy plus chemoradiation. Eight patients (32%) progressed during chemotherapy, including 7 with extrapancreatic metastases. Grade 3/4 hematologic toxicities were uncommon. Two patients sustained myocardial infarctions during chemotherapy, and 4 were hospitalized for infectious complications, although none in the setting of neutropenia. Median time to progression was 10.5 months and median survival was 13.5 months, with an estimated 1-year survival rate of 62%. Patients receiving all components of therapy had a median survival of 17.0 months.
      Conclusions: A strategy of initial fixed-dose rate gemcitabine-based chemotherapy, followed by chemoradiation, shows promising efficacy for treatment of locally advanced disease. A substantial proportion of patients will be identified early on as having extrapancreatic disease and spared the potential toxicities associated with radiation.


      To read this article in full you will need to make a payment
      ASTRO Member Login
      ASTRO Members, full access to the journal is a member benefit. Use your society credentials to access all journal content and features.
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Jemal A.
        • Siegel R.
        • Ward E.
        • et al.
        Cancer statistics, 2006.
        CA Cancer J Clin. 2006; 56: 106-130
        • Ceha H.M.
        • van Tienhoven G.
        • Gouma D.J.
        • et al.
        Feasibility and efficacy of high dose conformal radiotherapy for patients with locally advanced pancreatic carcinoma.
        Cancer. 2000; 89: 2222-2229
        • Rich T.A.
        Radiation therapy for pancreatic cancer: Eleven year experience at the JCRT.
        Int J Radiat Oncol Biol Phys. 1985; 11: 759-763
        • Ko A.H.
        • Dito E.
        • Schillinger B.
        • et al.
        Phase II study of fixed dose rate gemcitabine with cisplatin for metastatic adenocarcinoma of the pancreas.
        J Clin Oncol. 2006; 24: 379-385
        • The NCCN 2
        2006 pancreatic cancer guideline. NCCN, Jenkintown, PA2007
        • Moertel C.G.
        • Frytak S.
        • Hahn R.G.
        • et al.
        Therapy of locally unresectable pancreatic carcinoma: A randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group.
        Cancer. 1981; 48: 1705-1710
        • Gastrointestinal Tumor Study Group
        Treatment of locally unresectable carcinoma of the pancreas: Comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone.
        J Natl Cancer Inst. 1988; 80: 751-755
        • Klaassen D.J.
        • MacIntyre J.M.
        • Catton G.E.
        • et al.
        Treatment of locally unresectable cancer of the stomach and pancreas: A randomized comparison of 5-fluorouracil alone with radiation plus concurrent and maintenance 5-fluorouracil—an Eastern Cooperative Oncology Group study.
        J Clin Oncol. 1985; 3: 373-378
        • Chauffert B.
        • Mornex F.
        • Bonnetain F.
        • et al.
        Phase III trial comparing initial chemoradiotherapy (intermittent cisplatin and infusional 5-FU) followed by gemcitabine vs. gemcitabine alone in patients with locally advanced non metastatic pancreatic cancer: A FFCD-SFRO study.
        J Clin Oncol. 2006; 24: 4008
        • Burris 3rd, H.A.
        • Moore M.J.
        • Andersen J.
        • et al.
        Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: A randomized trial.
        J Clin Oncol. 1997; 15: 2403-2413
      1. Heinemann V, Quietzsch D, Gieseler F, et al. A phase III trial comparing gemcitabine plus cisplatin vs. gemcitabine alone in advanced pancreatic carcinoma. Proceedings of the American Society of Clinical Oncology. Vol 22. Chicago, IL: 2003; p 250.

        • Louvet C.
        • Labianca R.
        • Hammel P.
        • et al.
        Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: Results of a GERCOR and GISCAD phase III trial.
        J Clin Oncol. 2005; 23: 3509-3516
        • Grunewald R.
        • Kantarjian H.
        • Keating M.J.
        • et al.
        Pharmacologically directed design of the dose rate and schedule of 2‴,2‴-difluorodeoxycytidine (Gemcitabine) administration in leukemia.
        Cancer Res. 1990; 50: 6823-6826
        • Abbruzzese J.L.
        • Grunewald R.
        • Weeks E.A.
        • et al.
        A phase I clinical, plasma, and cellular pharmacology study of gemcitabine.
        J Clin Oncol. 1991; 9: 491-498
        • Tempero M.
        • Plunkett W.
        • Ruiz Van Haperen V.
        • et al.
        Randomized phase II comparison of dose-intense gemcitabine: Thirty-minute infusion and fixed dose rate infusion in patients with pancreatic adenocarcinoma.
        J Clin Oncol. 2003; 21: 3402-3408
      2. Poplin E, Levy DE, Berlin J, et al. Phase III trial of gemcitabine (30-minute infusion) versus gemcitabine (fixed-dose rate infusion) versus gemcitabine + oxaliplatin in patients with advanced pancreatic cancer (E6201). Proceedings of the American Society of Clinical Oncology. Vol 24. Atlanta, GA: 2006; p. 180s.

        • Vaishampayan U.N.
        • Ben-Josef E.
        • Philip P.A.
        • et al.
        A single-institution experience with concurrent capecitabine and radiation therapy in gastrointestinal malignancies.
        Int J Radiat Oncol Biol Phys. 2002; 53: 675-679
        • Schneider B.J.
        • Ben-Josef E.
        • McGinn C.J.
        • et al.
        Capecitabine and radiation therapy preceded and followed by combination chemotherapy in advanced pancreatic cancer.
        Int J Radiat Oncol Biol Phys. 2005; 63: 1325-1330
        • Sawada N.
        • Ishikawa T.
        • Sekiguchi F.
        • et al.
        X-ray irradiation induces thymidine phosphorylase and enhances the efficacy of capecitabine (Xeloda) in human cancer xenografts.
        Clin Cancer Res. 1999; 5: 2948-2953
        • Stefanidis D.
        • Grove K.D.
        • Schwesinger W.H.
        • et al.
        The current role of staging laparoscopy for adenocarcinoma of the pancreas: A review.
        Ann Oncol. 2006; 17: 189-199
        • Jimenez R.E.
        • Warshaw A.L.
        • Fernandez-Del Castillo C.
        Laparoscopy and peritoneal cytology in the staging of pancreatic cancer.
        J Hepatobiliary Pancreat Surg. 2000; 7: 15-20
        • Shoup M.
        • Winston C.
        • Brennan M.F.
        • et al.
        Is there a role for staging laparoscopy in patients with locally advanced, unresectable pancreatic adenocarcinoma?.
        J Gastrointest Surg. 2004; 8: 1068-1071
        • Wilkowski R.
        • Thoma M.
        • Duhmke E.
        • et al.
        Concurrent chemoradiotherapy with gemcitabine and cisplatin after incomplete (R1) resection of locally advanced pancreatic carcinoma.
        Int J Radiat Oncol Biol Phys. 2004; 58: 768-772
        • Blackstock A.W.
        • Tepper J.E.
        • Niedwiecki D.
        • et al.
        Cancer and leukemia group B (CALGB) 89805: Phase II chemoradiation trial using gemcitabine in patients with locoregional adenocarcinoma of the pancreas.
        Int J Gastrointest Cancer. 2003; 34: 107-116
        • Safran H.
        • Moore T.
        • Iannitti D.
        • et al.
        Paclitaxel and concurrent radiation for locally advanced pancreatic cancer.
        Int J Radiat Oncol Biol Phys. 2001; 49: 1275-1279
      3. Moore MJ, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer. A phase III trial of the National Cancer Institute of Canada Clinical Trials Group. Proceedings of the American Society of Clinical Oncology. Vol 23. Orlando, FL: 2005; p. 1.

        • Cunningham D.
        • Chau I.
        • Stocken D.
        • et al.
        Phase III randomised comparison of gemcitabine (GEM) versus gemcitabine plus capecitabine (GEM-CAP) in patients with advanced pancreatic cancer. ECCO 13, Paris2005


      Commenting Guidelines

      To submit a comment for a journal article, please use the space above and note the following:

      • We will review submitted comments as soon as possible, striving for within two business days.
      • This forum is intended for constructive dialogue. Comments that are commercial or promotional in nature, pertain to specific medical cases, are not relevant to the article for which they have been submitted, or are otherwise inappropriate will not be posted.
      • We require that commenters identify themselves with names and affiliations.
      • Comments must be in compliance with our Terms & Conditions.
      • Comments are not peer-reviewed.