Induction gemcitabine and stereotactic body radiotherapy for locally advanced nonmetastatic pancreas cancer.

PURPOSE Stereotactic body radiotherapy (SBRT) has been used successfully to treat patients with locally advanced pancreas cancer. However, many patients develop metastatic disease soon after diagnosis and may receive little benefit from such therapy. We therefore retrospectively analyzed a planned strategy of initial chemotherapy with restaging and then treatment for those patients with no evidence of metastatic progression with SBRT. METHODS AND MATERIALS Forty-seven patients received gemcitabine (1,000 mg/m(2) per week for 3 weeks then 1 week off) until tolerance, at least six cycles, or progression. Patients without metastases after two cycles were treated with SBRT (tolerance-based dose of 24-36 Gy in 3 fractions) between the third and fourth cycles without interrupting the chemotherapy cycles. RESULTS Eight of the 47 patients (17%) were found to have metastatic disease after two cycles of gemcitabine; the remaining 39 patients received SBRT. The median follow-up for survivors was 21 months (range, 6-36 months). The median overall survival for all patients who received SBRT was 20 months, and the median progression-free survival was 15 months. The local control rate was 85% (33 of 39 patients); and 54% of patients (21 of 39) developed metastases. Late Grade III toxicities such as GI bleeding and obstruction were observed in 9% (3/39) of patients. CONCLUSION For patients with locally advanced pancreas cancer, this strategy uses local therapy for those who are most likely to benefit from it and spares those patients with early metastatic progression from treatment. SBRT delivers such local therapy safely with minimal interruption to systemic chemotherapy, thereby potentially improving the outcome in these patients.

[1]  Christopher G Willett,et al.  Locally advanced pancreatic cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  P. Massucco,et al.  Phase II Trial of Primary Radiation Therapy and Concurrent Chemotherapy for Patients with Locally Advanced Pancreatic Cancer , 2005, Oncology.

[3]  A. Benson,et al.  A randomized phase III study of gemcitabine in combination with radiation therapy versus gemcitabine alone in patients with localized, unresectable pancreatic cancer: E4201 , 2008 .

[4]  H. Keen,et al.  ORAL HYPOGLYCÆMICS IN DIABETES MELLITUS , 1975, The Lancet.

[5]  K. Griffith,et al.  Phase I radiation dose-escalation trial of intensity-modulated radiotherapy (IMRT) with concurrent fixed dose-rate gemcitabine (FDR-G) for unresectable pancreatic cancer. , 2009, Journal of Clinical Oncology.

[6]  H. von der Maase,et al.  Phase-II study on stereotactic radiotherapy of locally advanced pancreatic carcinoma. , 2005, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[7]  J. Berlin,et al.  Phase III trial of gemcitabine (30-minute infusion) versus gemcitabine (fixed-dose-rate infusion [FDR]) versus gemcitabine + oxaliplatin (GEMOX) in patients with advanced pancreatic cancer (E6201). , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  E. Touboul,et al.  Impact of chemoradiotherapy after disease control with chemotherapy in locally advanced pancreatic adenocarcinoma in GERCOR phase II and III studies. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  J. Cameron,et al.  NCCN practice guidelines for pancreatic cancer. , 1997, Oncology.

[10]  B. Chauffert,et al.  Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Definitive results of the 2000-01 FFCD/SFRO study. , 2008, Annals of oncology : official journal of the European Society for Medical Oncology.

[11]  B. Erickson,et al.  Phase II Study of External Irradiation and Weekly Paclitaxel for Nonmetastatic, Unresectable Pancreatic Cancer: RTOG-98-12 , 2004, American journal of clinical oncology.

[12]  J. Roeske,et al.  Intensity-modulated radiotherapy in treatment of pancreatic and bile duct malignancies: toxicity and clinical outcome. , 2004, International journal of radiation oncology, biology, physics.

[13]  A Multi‐Institutional Comparative Trial of Radiation Therapy Alone and in Combination with 5‐fluorouracil for Locally Unresectable Pancreatic Carcinoma , 1979, Annals of surgery.

[14]  G. Schwartz,et al.  A phase I study of erlotinib in combination with gemcitabine and radiation in locally advanced, non-operable pancreatic adenocarcinoma. , 2008, Annals of oncology : official journal of the European Society for Medical Oncology.

[15]  Douglas B. Evans,et al.  Induction chemotherapy selects patients with locally advanced, unresectable pancreatic cancer for optimal benefit from consolidative chemoradiation therapy , 2007, Cancer.

[16]  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.

[17]  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.

[18]  D. Pleskow,et al.  Stereotactic body radiotherapy and gemcitabine for locally advanced pancreatic cancer. , 2010, International journal of radiation oncology, biology, physics.

[19]  Albert C Koong,et al.  Phase I study of stereotactic radiosurgery in patients with locally advanced pancreatic cancer. , 2004, International journal of radiation oncology, biology, physics.

[20]  R. Schilsky,et al.  A double-blind, placebo-controlled, randomized phase III trial of gemcitabine (G) plus bevacizumab (B) versus gemcitabine plus placebo (P) in patients (pts) with advanced pancreatic cancer (PC): A preliminary analysis of Cancer and Leukemia Group B (CALGB , 2007 .

[21]  J. Tepper,et al.  Cancer and leukemia group B (CALGB) 89805 , 2003 .

[22]  Bond-Smith Giles,et al.  Only women with symptoms need to have their breast implants removed, says government , 2012 .

[23]  Daniel T Chang,et al.  Stereotactic radiotherapy for unresectable adenocarcinoma of the pancreas , 2009, Cancer.

[24]  A. Jemal,et al.  Cancer Statistics, 2010 , 2010, CA: a cancer journal for clinicians.

[25]  Dwight E Heron,et al.  Stereotactic Body Radiotherapy in the Treatment of Advanced Adenocarcinoma of the Pancreas , 2011, American journal of clinical oncology.

[26]  A. Ko,et al.  Radiation therapy in operable and locally advanced pancreatic cancer. , 2010, Journal of the National Comprehensive Cancer Network : JNCCN.

[27]  D. Winchester,et al.  Pancreatic cancer: a report of treatment and survival trends for 100,313 patients diagnosed from 1985-1995, using the National Cancer Database. , 1999, Journal of the American College of Surgeons.

[28]  W. Curran,et al.  Phase II study of bevacizumab with concurrent capecitabine and radiation followed by maintenance gemcitabine and bevacizumab for locally advanced pancreatic cancer: Radiation Therapy Oncology Group RTOG 0411. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  N. Neerchal,et al.  Image-Guided Stereotactic Radiosurgery for Locally Advanced Pancreatic Adenocarcinoma Results of First 85 Patients , 2010, Journal of Gastrointestinal Surgery.

[30]  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.

[31]  J. Quivey,et al.  A phase II study of fixed-dose rate gemcitabine plus low-dose cisplatin followed by consolidative chemoradiation for locally advanced pancreatic cancer. , 2007, International journal of radiation oncology, biology, physics.

[32]  C. Moertel,et al.  Combined 5-fluorouracil and supervoltage radiation therapy of locally unresectable gastrointestinal cancer. , 1969, Lancet.

[33]  R. Schilsky,et al.  Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the Cancer and Leukemia Group B (CALGB 80303). , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[34]  R. Wolff,et al.  Multi-institutional Phase II Trial of Induction Cetuximab Gemcitabine and Oxaliplatin, followed by R , 2010 .

[35]  P. Catalano,et al.  Phase III, randomized study of gemcitabine and oxaliplatin versus gemcitabine (fixed-dose rate infusion) compared with gemcitabine (30-minute infusion) in patients with pancreatic carcinoma E6201: a trial of the Eastern Cooperative Oncology Group. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[36]  Jeffrey E. Lee,et al.  Phase I trial evaluating the safety of bevacizumab with concurrent radiotherapy and capecitabine in locally advanced pancreatic cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[37]  M. Saif,et al.  Is there an optimal neoadjuvant therapy for locally advanced pancreatic cancer? , 2007, JOP : Journal of the pancreas.

[38]  Y. Mataki,et al.  Length and quality of survival after external-beam radiotherapy with concurrent continuous 5-fluorouracil infusion for locally unresectable pancreatic cancer. , 2002, International journal of radiation oncology, biology, physics.

[39]  Paolo Francescon,et al.  Unresectable Locally Advanced Pancreatic Cancer: A Multimodal Treatment Using Neoadjuvant Chemoradiotherapy (Gemcitabine Plus Stereotactic Radiosurgery) and Subsequent Surgical Exploration , 2010, Annals of Surgical Oncology.

[40]  H. Ueno,et al.  Phase II study of radiotherapy combined with gemcitabine for locally advanced pancreatic cancer , 2004, British Journal of Cancer.

[41]  Wolfgang Schima,et al.  Pancreatic adenocarcinoma , 2006, European Radiology.

[42]  Quynh-Thu Le,et al.  Phase II study to assess the efficacy of conventionally fractionated radiotherapy followed by a stereotactic radiosurgery boost in patients with locally advanced pancreatic cancer. , 2005, International journal of radiation oncology, biology, physics.

[43]  T. Desser,et al.  Gemcitabine chemotherapy and single-fraction stereotactic body radiotherapy for locally advanced pancreatic cancer. , 2008, International journal of radiation oncology, biology, physics.