Phase II Trial of Cetuximab, Gemcitabine, and Oxaliplatin Followed by Chemoradiation With Cetuximab for Locally Advanced (T4) Pancreatic Adenocarcinoma: Correlation of Smad4(Dpc4) Immunostaining With Pattern of Disease Progression
Christopher H. Crane,Gauri R. Varadhachary,John S. Yordy,Gregg A Staerkel,Milind Javle,Howard Safran,Waqar M. Haque,Bridgett D. Hobbs,Sunil Krishnan,Jason B. Fleming,Prajnan Das,Jeffrey E. Lee,James L. Abbruzzese,Robert A. Wolff +13 more
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TLDR
This regimen appears effective and has acceptable toxicity and Prospective validation of Smad4(Dpc4) expression in cytology specimens as a predictive biomarker is warranted and may lead to personalized treatment strategies for patients with localized pancreatic cancer.Abstract:
Purpose This phase II trial was designed to assess the efficacy and safety of cetuximab, gemcitabine, and oxaliplatin followed by cetuximab, capecitabine, and radiation therapy in locally advanced pancreatic cancer (LAPC). Patients and Methods Treatment-naive eligible patients (n 69) received intravenous gemcitabine (1,000 mg/m 2 ) and oxaliplatin (100 mg/m 2 ) every 2 weeks for four doses, followed by radiation (50.4 Gy to the gross tumor only) with concurrent capecitabine (825 mg/m 2 twice daily on radiation treatment days). Cetuximab (500 mg/m 2 ) was started on day 1 of chemotherapy and was continued every 2 weeks during chemotherapy and chemoradiotherapy. Diagnostic cytology specimens were immunostained for Smad4(Dpc4) expression. Results Median overall survival time was 19.2 months (95% CI, 14.2 to 24.2 months), and 1-year, 2-year, and 4-year actuarial overall survival rates were 66.0%, 25.02%, and 11.3%, respectively. Acneiform rash correlated with improved survival (P .001), but initial CA19-9, borderline resectable initial stage, and surgical resection (n 7) did not. The 1-year and 2-year radiographic local progression rates were 22.8% and 61.0%, respectively. The worst acute toxic effects were GI toxicity (32% and 10% for grades 2 and 3, respectively); fatigue (26% and 6% for grades 2 and 3, respectively); sensory neuropathy (9% and 1% for grades 2 and 3, respectively); and acneiform rash (54% and 3% for grades 2 and 3, respectively). Smad4(Dpc4) expression correlated with a local rather than a distant dominant pattern of disease progression (P .016). Conclusion This regimen appears effective and has acceptable toxicity. The primary end point (1-year overall survival rate 45%) was met, with encouraging survival duration. Smad4(Dpc4) immunostaining correlated with the pattern of disease progression. Prospective validation of Smad4(Dpc4) expression in cytology specimens as a predictive biomarker is warranted and may lead to personalized treatment strategies for patients with localized pancreatic cancer. J Clin Oncol 29:3037-3043. © 2011 by American Society of Clinical Oncologyread more
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Recent Progress in Pancreatic Cancer
Christopher L. Wolfgang,Joseph M. Herman,Daniel A. Laheru,Alison P. Klein,Michael A. Erdek,Elliot K. Fishman,Ralph H. Hruban +6 more
TL;DR: In this paper, it is shown that multidisciplinary care that provides comprehensive and coordinated evaluation and treatment is the most effective way to manage patients with pancreatic cancer, and it is clear that multi-disciplinary care is the best way to care for patients.
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Randomized Controlled Trial of Interval-Compressed Chemotherapy for the Treatment of Localized Ewing Sarcoma: A Report From the Children's Oncology Group
Richard B. Womer,Daniel C. West,Mark Krailo,Paul S. Dickman,Bruce R. Pawel,Holcombe E. Grier,Karen J. Marcus,Scott L. Sailer,John H. Healey,John P. Dormans,Aaron R. Weiss +10 more
TL;DR: For localized Ewing sarcoma, chemotherapyadministered every 2 weeks is more effective than chemotherapy administered every 3 weeks, with no increase in toxicity.
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Addressing the challenges of pancreatic cancer: future directions for improving outcomes
Manuel Hidalgo,Stefano Cascinu,Jörg Kleeff,Roberto Labianca,J.-Matthias Löhr,John P. Neoptolemos,Francisco X. Real,Jean-Luc Van Laethem,Volker Heinemann +8 more
TL;DR: A number of approaches are proposed that may help to accelerate progress in treating patients with PDAC and may be expected to improve the quality of life and survival for those suffering from this devastating disease.
Journal ArticleDOI
Myeloproliferative Neoplasm (MPN) Symptom Assessment Form Total Symptom Score: Prospective International Assessment of an Abbreviated Symptom Burden Scoring System Among Patients With MPNs
Robyn M. Emanuel,Amylou C. Dueck,Holly L. Geyer,Jean-Jacques Kiladjian,Stefanie Slot,Sonja Zweegman,Peter A. W. te Boekhorst,Suzan Commandeur,Harry C. Schouten,Federico Sackmann,Ana Kerguelen Fuentes,Dolores Hernández-Maraver,Heike L. Pahl,Martin Griesshammer,Frank Stegelmann,Konstanze Doehner,Thomas Lehmann,Karin Bonatz,Andreas Reiter,Françoise Boyer,Gabriel Etienne,Jean Christophe Ianotto,Dana Ranta,Lydia Roy,Jean-Yves Cahn,Claire N. Harrison,Deepti Radia,Pablo J. Muxi,Norman Maldonado,Carlos Besses,Francisco Cervantes,Peter L. Johansson,Tiziano Barbui,Giovanni Barosi,Alessandro M. Vannucchi,Francesco Passamonti,Bjorn Andreasson,Maria L Ferarri,Alessandro Rambaldi,Jan Samuelsson,Gunnar Birgegård,Ayalew Tefferi,Ruben A. Mesa +42 more
TL;DR: The MPN-SAF TSS is a concise, valid, and accurate assessment of MPN symptom burden with demonstrated clinical utility in the largest prospective MPN symptoms study to date.
Journal ArticleDOI
Locally Advanced, Unresectable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline
Edward P. Balaban,Pamela B. Mangu,Alok A. Khorana,Manish A. Shah,Somnath Mukherjee,Christopher H. Crane,Milind Javle,Jennifer R. Eads,Peter J. Allen,Andrew H. Ko,Anitra Engebretson,Joseph M. Herman,John H. Strickler,Al B. Benson,Susan G. Urba,Nelson S. Yee +15 more
TL;DR: The gemcitabine-based combinations and treatments recommended in the metastatic setting have not been evaluated in randomized controlled trials involving locally advanced, unresectable pancreatic cancer.
References
More filters
Journal ArticleDOI
Reporting results of cancer treatment.
TL;DR: Recommendations have been developed for standardized approaches to the recording of baseline data relating to the patient, the tumor, laboratory and radiologic data, the reporting of treatment, grading of acute and subacute toxicity, reporting of response, recurrence and disease‐free interval, and reporting results of therapy.
Journal ArticleDOI
Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer.
David Cunningham,Yves Humblet,Salvatore Siena,David Khayat,Harry Bleiberg,Armando Santoro,D. Bets,M. Mueser,Andreas Harstrick,Chris Verslype,Ian Chau,Eric Van Cutsem +11 more
TL;DR: Cetuximab has clinically significant activity when given alone or in combination with irinotecan in patients with ir inotecans-refractory colorectal cancer.
Journal ArticleDOI
DPC4 Gene Status of the Primary Carcinoma Correlates With Patterns of Failure in Patients With Pancreatic Cancer
Christine A. Iacobuzio-Donahue,Baojin Fu,Shinichi Yachida,Mingde Luo,Hisashi Abe,Clark M. Henderson,Felip Vilardell,Zheng Wang,Jesse Keller,Priya Banerjee,Joseph M. Herman,John L. Cameron,Charles J. Yeo,Marc K. Halushka,James R. Eshleman,Marian Raben,Alison P. Klein,Ralph H. Hruban,Manuel Hidalgo,Daniel A. Laheru +19 more
TL;DR: Pancreatic cancers are represented by distinct genetic subtypes with significantly different patterns of failure, and determinations of DPC4 status at initial diagnosis may be of value in stratifying patients into treatment regimens related to local control versus systemic therapy.
Journal ArticleDOI
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
Christophe Louvet,R. Labianca,Pascal Hammel,G. Lledo,Maria Giulia Zampino,Thierry André,Alberto Zaniboni,Michel Ducreux,Enrico Aitini,Julien Taieb,R. Faroux,C. Lepere,A. de Gramont +12 more
TL;DR: A phase III study comparing GemOx with Gem alone in advanced pancreatic cancer, confirming the efficacy and safety of GemOx and failing to demonstrate a statistically significant advantage in terms of OS compared with Gem.
Journal ArticleDOI
Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas.
Douglas B. Evans,Tyvin A. Rich,David R. Byrd,Karen R. Cleary,John H. Connelly,Bernard Levin,Chusilp Charnsangavej,Claudia J. Fenoglio,Frederick C. Ames +8 more
TL;DR: The results suggest that pancreaticoduodenectomy can be performed with a low incidence of complications after chemoradiation for localized adenocarcinoma of the pancreas.
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