Efficacy, Safety, and Biomarkers of Neoadjuvant Bevacizumab, Radiation Therapy, and Fluorouracil in Rectal Cancer: A Multidisciplinary Phase II Study
Christopher G. Willett,Dan G. Duda,Emmanuelle di Tomaso,Yves Boucher,Marek Ancukiewicz,Dushyant V. Sahani,Johanna Lahdenranta,Daniel C. Chung,Alan J. Fischman,Gregory Y. Lauwers,Paul C. Shellito,Brian G. Czito,Terence Z. Wong,Erik K. Paulson,Martin Poleski,Zeljko Vujaskovic,Rex C. Bentley,Helen X. Chen,Jeffrey W. Clark,Rakesh K. Jain +19 more
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TLDR
Bvacizumab with chemoradiotherapy appears safe and active and yields promising survival results in locally advanced rectal cancer.Abstract:
Purpose To assess the safety and efficacy of neoadjuvant bevacizumab with standard chemoradiotherapy in locally advanced rectal cancer and explore biomarkers for response. Patients and Methods In a phase I/II study, 32 patients received four cycles of therapy consisting of: bevacizumab infusion (5 or 10 mg/kg) on day 1 of each cycle; fluorouracil infusion (225 mg/m2/24 hours) during cycles 2 to 4; external-beam irradiation (50.4 Gy in 28 fractions over 5.5 weeks); and surgery 7 to 10 weeks after completion of all therapies. We measured molecular, cellular, and physiologic biomarkers before treatment, during bevacizumab monotherapy, and during and after combination therapy. Results Tumors regressed from a mass with mean size of 5 cm (range, 3 to 12 cm) to an ulcer/scar with mean size of 2.4 cm (range, 0.7 to 6.0 cm) in all 32 patients. Histologic examination revealed either no cancer or varying numbers of scattered cancer cells in a bed of fibrosis at the primary site. This treatment resulted in an actuari...read more
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References
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Journal ArticleDOI
Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer
Herbert Hurwitz,Louis Fehrenbacher,William Novotny,Thomas Cartwright,John D. Hainsworth,W. Heim,Jordan Berlin,Ari David Baron,Susan Griffing,Eric Holmgren,Napoleone Ferrara,Gwen Fyfe,Beth Rogers,Robert W. Ross,Fairooz F. Kabbinavar +14 more
TL;DR: The addition of bevacizumab to fluorouracil-based combination chemotherapy results in statistically significant and clinically meaningful improvement in survival among patients with metastatic colorectal cancer.
Journal ArticleDOI
Preoperative versus Postoperative Chemoradiotherapy for Rectal Cancer
Rolf Sauer,Heinz Becker,Werner Hohenberger,Claus Rödel,Christian Wittekind,Rainer Fietkau,Peter Martus,Jörg Tschmelitsch,Eva Hager,Clemens F. Hess,Torsten Liersch,Heinz Schmidberger,Rudolf Raab +12 more
TL;DR: Preoperative chemoradiotherapy, as compared with postoperative cheMoradi therapy, improved local control and was associated with reduced toxicity but did not improve overall survival.
Journal ArticleDOI
Normalization of Tumor Vasculature: An Emerging Concept in Antiangiogenic Therapy
TL;DR: Emerging evidence supporting an alternative hypothesis is reviewed—that certain antiangiogenic agents can also transiently “normalize” the abnormal structure and function of tumor vasculature to make it more efficient for oxygen and drug delivery.
Journal ArticleDOI
Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer
Christopher G. Willett,Yves Boucher,Emmanuelle di Tomaso,Dan G. Duda,Lance L. Munn,Ricky T. Tong,Daniel C. Chung,Dushyant V. Sahani,Sanjeeva P. Kalva,Sergey V. Kozin,Mari Mino,Kenneth S. Cohen,David T. Scadden,Alan C. Hartford,Alan J. Fischman,Jeffrey W. Clark,David P. Ryan,Andrew X. Zhu,Lawrence S. Blaszkowsky,Helen X. Chen,Paul C. Shellito,Gregory Y Lauwers,Rakesh K. Jain +22 more
TL;DR: It is shown that a single infusion of the VEGF-specific antibody bevacizumab decreases tumor perfusion, vascular volume, microvascular density, interstitial fluid pressure and the number of viable, circulating endothelial and progenitor cells, and increases the fraction of vessels with pericyte coverage in rectal carcinoma patients.
Journal Article
Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer
Christopher G. Willett,Yves Boucher,Emmanuelle di Tomaso,Dan G. Duda,Lance L. Munn,Ricky T. Tong,Daniel C. Chung,Dushyant V. Sahani,Sanjeeva P. Kalva,Sergey V. Kozin,Mari Mino,Kenneth S. Cohen,David T. Scadden,Alan C. Hartford,Alan J. Fischman,Jeffrey W. Clark,David P. Ryan,Andrew X. Zhu,Lawrence S. Blaszkowsky,Helen X. Chen,Paul C. Shellito,Gregory Y Lauwers,Rakesh K. Jain +22 more
TL;DR: In this article, a single infusion of the VEGF-specific antibody bevacizumab decreases tumor perfusion, vascular volume, microvascular density, interstitial fluid pressure and the number of viable, circulating endothelial and progenitor cells, and increases the fraction of vessels with pericyte coverage in rectal carcinoma patients.
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