Impact of chemoradiotherapy after disease control with chemotherapy in locally advanced pancreatic adenocarcinoma in GERCOR phase II and III studies.

PURPOSE The management of locally advanced (LA) pancreatic cancer patients remains controversial. To select patients who could benefit from chemoradiotherapy (CRT), the therapeutic strategy used by the Groupe Coopérateur Multidisciplinaire en Oncologie (GERCOR) consisted of initial chemotherapy (CT) for at least 3 months. The decision to administer CRT or continue CT in nonprogressive patients was the investigator's choice. PATIENTS AND METHODS Retrospective analysis of outcome in 181 patients with LA pancreatic cancer (76 women and 105 men; mean age, 61 years; range, 37 to 85 years) enrolled onto prospective phase II and III GERCOR studies was performed to compare the survival of patients who received CRT with that of patients who continued CT alone. RESULTS Median progression-free survival (PFS) and overall survival (OS) times for the 181 patients were 6.3 and 11.4 months, respectively. Fifty-three patients (29.3%) had metastatic disease after 3 months of CT and were not eligible for CRT. Among the 128 remaining patients (70.3%) who had no disease progression and who were, therefore, eligible for CRT, 72 (56%) received CRT (group A), whereas 56 (44%) continued with CT (group B). The two groups were balanced for initial characteristics (performance status, sex, age, and type of CT), as well as for induction CT results. In groups A and B, the median PFS times were 10.8 and 7.4 months, respectively (P = .005), and the median OS times were 15.0 and 11.7 months, respectively (P = .0009). CONCLUSION These results suggest that, after control of disease by initial CT, CRT could significantly improve survival in patients with LA pancreatic cancer compared with CT alone. A prospective phase III study is ongoing to evaluate this strategy.

[1]  R. Wolff,et al.  Neoadjuvant chemotherapy improves outcomes of chemoradiation therapy for locally advanced pancreatic cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  B. Chauffert,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. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  A. Chang,et al.  Capecitabine and radiation therapy preceded and followed by combination chemotherapy in advanced pancreatic cancer. , 2005, International journal of radiation oncology, biology, physics.

[4]  S. Lipsitz,et al.  A randomized phase III study of radiotherapy alone or with 5-fluorouracil and mitomycin-C in patients with locally advanced adenocarcinoma of the pancreas: Eastern Cooperative Oncology Group study E8282. , 2005, International journal of radiation oncology, biology, physics.

[5]  L. Case,et al.  Phase II Trial of Induction Gemcitabine/CPT-11 Followed by a Twice-Weekly Infusion of Gemcitabine and Concurrent External Beam Radiation for the Treatment of Locally Advanced Pancreatic Cancer , 2005, American journal of clinical oncology.

[6]  R. Labianca,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. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  M. Fernex [The article by C. Hill and F. Doyon, The frequency of cancer in France in 2000 and trends after 1950, in Bulletin du Cancer 2005;92:7-11]. , 2005, Bulletin du cancer.

[8]  C. Hill,et al.  La fréquence des cancers en France en 2000 et son évolution depuis 1950 , 2005 .

[9]  C. Hill,et al.  [The frequency of cancer in France in year 2000, and trends since 1950]. , 2005, Bulletin du cancer.

[10]  W. Miller,et al.  Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  P. Hammel,et al.  Phase II study of leucovorin, 5-fluorouracil and gemcitabine for locally advanced and metastatic pancreatic cancer (FOLFUGEM 2). , 2004, Gastroenterologie clinique et biologique.

[12]  E. Van Cutsem,et al.  Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  P. Philip,et al.  Phase II study of gemcitabine, cisplatin, and infusional fluorouracil in advanced pancreatic cancer. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  M. Dimopoulos,et al.  Treatment of pancreatic cancer with a combination of irinotecan (CPT-11) and gemcitabine: a multicenter phase II study by the Greek Cooperative Group for Pancreatic Cancer. , 2003, Annals of oncology : official journal of the European Society for Medical Oncology.

[15]  G. Hédelin,et al.  Cancer incidence and mortality in France over the period 1978-2000. , 2003, Revue d'epidemiologie et de sante publique.

[16]  A. Kuten,et al.  Phase II study of gemcitabine combined with radiation therapy in patients with localized, unresectable pancreatic cancer , 2002, Journal of surgical oncology.

[17]  P. Hammel,et al.  Gemcitabine combined with oxaliplatin in advanced pancreatic adenocarcinoma: final results of a GERCOR multicenter phase II study. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  R. Talamini,et al.  Radiotherapy and continuous infusion 5-fluorouracil in patients with nonresectable pancreatic carcinoma. , 2001, International journal of radiation oncology, biology, physics.

[19]  M. Reni,et al.  Definitive results of a phase II trial of cisplatin, epirubicin, continuous-infusion fluorouracil, and gemcitabine in stage IV pancreatic adenocarcinoma. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  P. Ruszniewski,et al.  Phase II trial of bimonthly leucovorin, 5-fluorouracil and gemcitabine for advanced pancreatic adenocarcinoma (FOLFUGEM). , 2001, Annals of oncology : official journal of the European Society for Medical Oncology.

[21]  E. Touboul,et al.  Combined radiotherapy and chemotherapy (cisplatin and 5-fluorouracil) as palliative treatment for localized unresectable or adjuvant treatment for resected pancreatic adenocarcinoma: results of a feasibility study. , 2000, International journal of radiation oncology, biology, physics.

[22]  W. Scheithauer,et al.  Treatment of unresectable, locally advanced pancreatic adenocarcinoma with combined radiochemotherapy with 5-fluorouracil, leucovorin and cisplatin , 1999, British Journal of Cancer.

[23]  I. Awad,et al.  Protracted 5-Fluorouracil Infusion with Concurrent Radiotherapy as a Treatment for Locally Advanced Pancreatic Carcinoma , 2000 .

[24]  J. Gligorov,et al.  [Adenocarcinoma of the pancreas. General characteristics]. , 1998, Presse medicale.

[25]  D. V. Von Hoff,et al.  Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  D. V. Von Hoff,et al.  A phase II trial of gemcitabine in patients with 5-FU-refractory pancreas cancer. , 1996, Annals of oncology : official journal of the European Society for Medical Oncology.

[27]  D. Neuberg,et al.  Protracted intravenous fluorouracil infusion with radiation therapy in the management of localized pancreaticobiliary carcinoma: a phase I Eastern Cooperative Oncology Group Trial. , 1995, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[28]  Birgir Gudjonsson,et al.  Cancer of the pancreas: 50 years of surgery , 1987, Cancer.

[29]  P. Engstrom,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. , 1985, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[30]  J. Barkin,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 , 1981, Cancer.