title: Cetuximab Plus Chemoradiotherapy in Immunocompetent Patients With Anal Carcinoma: A Phase II Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group Trial (E3205).
abstract: Purpose Squamous cell carcinoma of the anal canal (SCCAC) is characterized by high locoregional failure (LRF) rates after sphincter-preserving definitive chemoradiation (CRT) and is typically associated with anogenital human papilloma virus infection. Because cetuximab enhances the effect of radiation therapy in human papilloma virus-associated oropharyngeal squamous cell carcinoma, we hypothesized that adding cetuximab to CRT would reduce LRF in SCCAC. Methods Sixty-one patients with stage I to III SCCAC received CRT including cisplatin, fluorouracil, and radiation therapy to the primary tumor and regional lymph nodes (45 to 54 Gy) plus eight once-weekly doses of concurrent cetuximab. The study was designed to detect at least a 50% reduction in 3-year LRF rate (one-sided α, 0.10; power 90%), assuming a 35% LRF rate from historical data. Results Poor risk features included stage III disease in 64% and male sex in 20%. The 3-year LRF rate was 23% (95% CI, 13% to 36%; one-sided P = .03) by binomial proportional estimate using the prespecified end point and 21% (95% CI, 7% to 26%) by Kaplan-Meier estimate in a post hoc analysis using methods consistent with historical data. Three-year rates were 68% (95% CI, 55% to 79%) for progression-free survival and 83% (95% CI, 71% to 91%) for overall survival. Grade 4 toxicity occurred in 32%, and 5% had treatment-associated deaths. Conclusion Although the addition of cetuximab to chemoradiation for SCCAC was associated with lower LRF rates than historical data with CRT alone, toxicity was substantial, and LRF still occurs in approximately 20%, indicating the continued need for more effective and less toxic therapies.
authors.affiliation: Madhur K. Garg, Joseph A. Sparano, and Shalom Kalnicki, Montefiore Medical Center, Albert Einstein College of Medicine, Montefiore-Einstein Center for Cancer Care, Bronx, NY; Fengmin Zhao, Dana Farber Cancer Institute, Boston, MA; Joel Palefsky, University of California, San Francisco, CA; Richard Whittington, Philadelphia VA Medical Center; Edith P. Mitchell, Thomas Jefferson University, Philadelphia, PA; Mary F. Mulcahy and Al B. Benson III, Northwestern University, Chicago, IL; Karin I. Armstrong, United Hospital, Woodbury, MN; Nassim H. Nabbout, Cancer Center of Kansas, Wichita, KS; Bassel F. El-Rayes, Emory University, Atlanta, GA; Adedayo A. Onitilo, Marshfield Clinic, Marshfield, WI; Daniel J. Moriarty, Overlook Medical Center, Summit, NJ; and Thomas J. Fitzgerald, Imaging and Radiation Oncology Core, Quality Assurance Review Center, Providence, RI.
authors.forename: Madhur K
authors.initials: MK
authors.lastname: Garg
authors.affiliation: Madhur K. Garg, Joseph A. Sparano, and Shalom Kalnicki, Montefiore Medical Center, Albert Einstein College of Medicine, Montefiore-Einstein Center for Cancer Care, Bronx, NY; Fengmin Zhao, Dana Farber Cancer Institute, Boston, MA; Joel Palefsky, University of California, San Francisco, CA; Richard Whittington, Philadelphia VA Medical Center; Edith P. Mitchell, Thomas Jefferson University, Philadelphia, PA; Mary F. Mulcahy and Al B. Benson III, Northwestern University, Chicago, IL; Karin I. Armstrong, United Hospital, Woodbury, MN; Nassim H. Nabbout, Cancer Center of Kansas, Wichita, KS; Bassel F. El-Rayes, Emory University, Atlanta, GA; Adedayo A. Onitilo, Marshfield Clinic, Marshfield, WI; Daniel J. Moriarty, Overlook Medical Center, Summit, NJ; and Thomas J. Fitzgerald, Imaging and Radiation Oncology Core, Quality Assurance Review Center, Providence, RI.
authors.forename: Fengmin
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Madhur K. Garg, Joseph A. Sparano, and Shalom Kalnicki, Montefiore Medical Center, Albert Einstein College of Medicine, Montefiore-Einstein Center for Cancer Care, Bronx, NY; Fengmin Zhao, Dana Farber Cancer Institute, Boston, MA; Joel Palefsky, University of California, San Francisco, CA; Richard Whittington, Philadelphia VA Medical Center; Edith P. Mitchell, Thomas Jefferson University, Philadelphia, PA; Mary F. Mulcahy and Al B. Benson III, Northwestern University, Chicago, IL; Karin I. Armstrong, United Hospital, Woodbury, MN; Nassim H. Nabbout, Cancer Center of Kansas, Wichita, KS; Bassel F. El-Rayes, Emory University, Atlanta, GA; Adedayo A. Onitilo, Marshfield Clinic, Marshfield, WI; Daniel J. Moriarty, Overlook Medical Center, Summit, NJ; and Thomas J. Fitzgerald, Imaging and Radiation Oncology Core, Quality Assurance Review Center, Providence, RI.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Sparano
authors.affiliation: Madhur K. Garg, Joseph A. Sparano, and Shalom Kalnicki, Montefiore Medical Center, Albert Einstein College of Medicine, Montefiore-Einstein Center for Cancer Care, Bronx, NY; Fengmin Zhao, Dana Farber Cancer Institute, Boston, MA; Joel Palefsky, University of California, San Francisco, CA; Richard Whittington, Philadelphia VA Medical Center; Edith P. Mitchell, Thomas Jefferson University, Philadelphia, PA; Mary F. Mulcahy and Al B. Benson III, Northwestern University, Chicago, IL; Karin I. Armstrong, United Hospital, Woodbury, MN; Nassim H. Nabbout, Cancer Center of Kansas, Wichita, KS; Bassel F. El-Rayes, Emory University, Atlanta, GA; Adedayo A. Onitilo, Marshfield Clinic, Marshfield, WI; Daniel J. Moriarty, Overlook Medical Center, Summit, NJ; and Thomas J. Fitzgerald, Imaging and Radiation Oncology Core, Quality Assurance Review Center, Providence, RI.
authors.forename: Joel
authors.initials: J
authors.lastname: Palefsky
authors.affiliation: Madhur K. Garg, Joseph A. Sparano, and Shalom Kalnicki, Montefiore Medical Center, Albert Einstein College of Medicine, Montefiore-Einstein Center for Cancer Care, Bronx, NY; Fengmin Zhao, Dana Farber Cancer Institute, Boston, MA; Joel Palefsky, University of California, San Francisco, CA; Richard Whittington, Philadelphia VA Medical Center; Edith P. Mitchell, Thomas Jefferson University, Philadelphia, PA; Mary F. Mulcahy and Al B. Benson III, Northwestern University, Chicago, IL; Karin I. Armstrong, United Hospital, Woodbury, MN; Nassim H. Nabbout, Cancer Center of Kansas, Wichita, KS; Bassel F. El-Rayes, Emory University, Atlanta, GA; Adedayo A. Onitilo, Marshfield Clinic, Marshfield, WI; Daniel J. Moriarty, Overlook Medical Center, Summit, NJ; and Thomas J. Fitzgerald, Imaging and Radiation Oncology Core, Quality Assurance Review Center, Providence, RI.
authors.forename: Richard
authors.initials: R
authors.lastname: Whittington
authors.affiliation: Madhur K. Garg, Joseph A. Sparano, and Shalom Kalnicki, Montefiore Medical Center, Albert Einstein College of Medicine, Montefiore-Einstein Center for Cancer Care, Bronx, NY; Fengmin Zhao, Dana Farber Cancer Institute, Boston, MA; Joel Palefsky, University of California, San Francisco, CA; Richard Whittington, Philadelphia VA Medical Center; Edith P. Mitchell, Thomas Jefferson University, Philadelphia, PA; Mary F. Mulcahy and Al B. Benson III, Northwestern University, Chicago, IL; Karin I. Armstrong, United Hospital, Woodbury, MN; Nassim H. Nabbout, Cancer Center of Kansas, Wichita, KS; Bassel F. El-Rayes, Emory University, Atlanta, GA; Adedayo A. Onitilo, Marshfield Clinic, Marshfield, WI; Daniel J. Moriarty, Overlook Medical Center, Summit, NJ; and Thomas J. Fitzgerald, Imaging and Radiation Oncology Core, Quality Assurance Review Center, Providence, RI.
authors.forename: Edith P
authors.initials: EP
authors.lastname: Mitchell
authors.affiliation: Madhur K. Garg, Joseph A. Sparano, and Shalom Kalnicki, Montefiore Medical Center, Albert Einstein College of Medicine, Montefiore-Einstein Center for Cancer Care, Bronx, NY; Fengmin Zhao, Dana Farber Cancer Institute, Boston, MA; Joel Palefsky, University of California, San Francisco, CA; Richard Whittington, Philadelphia VA Medical Center; Edith P. Mitchell, Thomas Jefferson University, Philadelphia, PA; Mary F. Mulcahy and Al B. Benson III, Northwestern University, Chicago, IL; Karin I. Armstrong, United Hospital, Woodbury, MN; Nassim H. Nabbout, Cancer Center of Kansas, Wichita, KS; Bassel F. El-Rayes, Emory University, Atlanta, GA; Adedayo A. Onitilo, Marshfield Clinic, Marshfield, WI; Daniel J. Moriarty, Overlook Medical Center, Summit, NJ; and Thomas J. Fitzgerald, Imaging and Radiation Oncology Core, Quality Assurance Review Center, Providence, RI.
authors.forename: Mary F
authors.initials: MF
authors.lastname: Mulcahy
authors.affiliation: Madhur K. Garg, Joseph A. Sparano, and Shalom Kalnicki, Montefiore Medical Center, Albert Einstein College of Medicine, Montefiore-Einstein Center for Cancer Care, Bronx, NY; Fengmin Zhao, Dana Farber Cancer Institute, Boston, MA; Joel Palefsky, University of California, San Francisco, CA; Richard Whittington, Philadelphia VA Medical Center; Edith P. Mitchell, Thomas Jefferson University, Philadelphia, PA; Mary F. Mulcahy and Al B. Benson III, Northwestern University, Chicago, IL; Karin I. Armstrong, United Hospital, Woodbury, MN; Nassim H. Nabbout, Cancer Center of Kansas, Wichita, KS; Bassel F. El-Rayes, Emory University, Atlanta, GA; Adedayo A. Onitilo, Marshfield Clinic, Marshfield, WI; Daniel J. Moriarty, Overlook Medical Center, Summit, NJ; and Thomas J. Fitzgerald, Imaging and Radiation Oncology Core, Quality Assurance Review Center, Providence, RI.
authors.forename: Karin I
authors.initials: KI
authors.lastname: Armstrong
authors.affiliation: Madhur K. Garg, Joseph A. Sparano, and Shalom Kalnicki, Montefiore Medical Center, Albert Einstein College of Medicine, Montefiore-Einstein Center for Cancer Care, Bronx, NY; Fengmin Zhao, Dana Farber Cancer Institute, Boston, MA; Joel Palefsky, University of California, San Francisco, CA; Richard Whittington, Philadelphia VA Medical Center; Edith P. Mitchell, Thomas Jefferson University, Philadelphia, PA; Mary F. Mulcahy and Al B. Benson III, Northwestern University, Chicago, IL; Karin I. Armstrong, United Hospital, Woodbury, MN; Nassim H. Nabbout, Cancer Center of Kansas, Wichita, KS; Bassel F. El-Rayes, Emory University, Atlanta, GA; Adedayo A. Onitilo, Marshfield Clinic, Marshfield, WI; Daniel J. Moriarty, Overlook Medical Center, Summit, NJ; and Thomas J. Fitzgerald, Imaging and Radiation Oncology Core, Quality Assurance Review Center, Providence, RI.
authors.forename: Nassim H
authors.initials: NH
authors.lastname: Nabbout
authors.affiliation: Madhur K. Garg, Joseph A. Sparano, and Shalom Kalnicki, Montefiore Medical Center, Albert Einstein College of Medicine, Montefiore-Einstein Center for Cancer Care, Bronx, NY; Fengmin Zhao, Dana Farber Cancer Institute, Boston, MA; Joel Palefsky, University of California, San Francisco, CA; Richard Whittington, Philadelphia VA Medical Center; Edith P. Mitchell, Thomas Jefferson University, Philadelphia, PA; Mary F. Mulcahy and Al B. Benson III, Northwestern University, Chicago, IL; Karin I. Armstrong, United Hospital, Woodbury, MN; Nassim H. Nabbout, Cancer Center of Kansas, Wichita, KS; Bassel F. El-Rayes, Emory University, Atlanta, GA; Adedayo A. Onitilo, Marshfield Clinic, Marshfield, WI; Daniel J. Moriarty, Overlook Medical Center, Summit, NJ; and Thomas J. Fitzgerald, Imaging and Radiation Oncology Core, Quality Assurance Review Center, Providence, RI.
authors.forename: Shalom
authors.initials: S
authors.lastname: Kalnicki
authors.affiliation: Madhur K. Garg, Joseph A. Sparano, and Shalom Kalnicki, Montefiore Medical Center, Albert Einstein College of Medicine, Montefiore-Einstein Center for Cancer Care, Bronx, NY; Fengmin Zhao, Dana Farber Cancer Institute, Boston, MA; Joel Palefsky, University of California, San Francisco, CA; Richard Whittington, Philadelphia VA Medical Center; Edith P. Mitchell, Thomas Jefferson University, Philadelphia, PA; Mary F. Mulcahy and Al B. Benson III, Northwestern University, Chicago, IL; Karin I. Armstrong, United Hospital, Woodbury, MN; Nassim H. Nabbout, Cancer Center of Kansas, Wichita, KS; Bassel F. El-Rayes, Emory University, Atlanta, GA; Adedayo A. Onitilo, Marshfield Clinic, Marshfield, WI; Daniel J. Moriarty, Overlook Medical Center, Summit, NJ; and Thomas J. Fitzgerald, Imaging and Radiation Oncology Core, Quality Assurance Review Center, Providence, RI.
authors.forename: Bassel F
authors.initials: BF
authors.lastname: El-Rayes
authors.affiliation: Madhur K. Garg, Joseph A. Sparano, and Shalom Kalnicki, Montefiore Medical Center, Albert Einstein College of Medicine, Montefiore-Einstein Center for Cancer Care, Bronx, NY; Fengmin Zhao, Dana Farber Cancer Institute, Boston, MA; Joel Palefsky, University of California, San Francisco, CA; Richard Whittington, Philadelphia VA Medical Center; Edith P. Mitchell, Thomas Jefferson University, Philadelphia, PA; Mary F. Mulcahy and Al B. Benson III, Northwestern University, Chicago, IL; Karin I. Armstrong, United Hospital, Woodbury, MN; Nassim H. Nabbout, Cancer Center of Kansas, Wichita, KS; Bassel F. El-Rayes, Emory University, Atlanta, GA; Adedayo A. Onitilo, Marshfield Clinic, Marshfield, WI; Daniel J. Moriarty, Overlook Medical Center, Summit, NJ; and Thomas J. Fitzgerald, Imaging and Radiation Oncology Core, Quality Assurance Review Center, Providence, RI.
authors.forename: Adedayo A
authors.initials: AA
authors.lastname: Onitilo
authors.affiliation: Madhur K. Garg, Joseph A. Sparano, and Shalom Kalnicki, Montefiore Medical Center, Albert Einstein College of Medicine, Montefiore-Einstein Center for Cancer Care, Bronx, NY; Fengmin Zhao, Dana Farber Cancer Institute, Boston, MA; Joel Palefsky, University of California, San Francisco, CA; Richard Whittington, Philadelphia VA Medical Center; Edith P. Mitchell, Thomas Jefferson University, Philadelphia, PA; Mary F. Mulcahy and Al B. Benson III, Northwestern University, Chicago, IL; Karin I. Armstrong, United Hospital, Woodbury, MN; Nassim H. Nabbout, Cancer Center of Kansas, Wichita, KS; Bassel F. El-Rayes, Emory University, Atlanta, GA; Adedayo A. Onitilo, Marshfield Clinic, Marshfield, WI; Daniel J. Moriarty, Overlook Medical Center, Summit, NJ; and Thomas J. Fitzgerald, Imaging and Radiation Oncology Core, Quality Assurance Review Center, Providence, RI.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Moriarty
authors.affiliation: Madhur K. Garg, Joseph A. Sparano, and Shalom Kalnicki, Montefiore Medical Center, Albert Einstein College of Medicine, Montefiore-Einstein Center for Cancer Care, Bronx, NY; Fengmin Zhao, Dana Farber Cancer Institute, Boston, MA; Joel Palefsky, University of California, San Francisco, CA; Richard Whittington, Philadelphia VA Medical Center; Edith P. Mitchell, Thomas Jefferson University, Philadelphia, PA; Mary F. Mulcahy and Al B. Benson III, Northwestern University, Chicago, IL; Karin I. Armstrong, United Hospital, Woodbury, MN; Nassim H. Nabbout, Cancer Center of Kansas, Wichita, KS; Bassel F. El-Rayes, Emory University, Atlanta, GA; Adedayo A. Onitilo, Marshfield Clinic, Marshfield, WI; Daniel J. Moriarty, Overlook Medical Center, Summit, NJ; and Thomas J. Fitzgerald, Imaging and Radiation Oncology Core, Quality Assurance Review Center, Providence, RI.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Fitzgerald
authors.affiliation: Madhur K. Garg, Joseph A. Sparano, and Shalom Kalnicki, Montefiore Medical Center, Albert Einstein College of Medicine, Montefiore-Einstein Center for Cancer Care, Bronx, NY; Fengmin Zhao, Dana Farber Cancer Institute, Boston, MA; Joel Palefsky, University of California, San Francisco, CA; Richard Whittington, Philadelphia VA Medical Center; Edith P. Mitchell, Thomas Jefferson University, Philadelphia, PA; Mary F. Mulcahy and Al B. Benson III, Northwestern University, Chicago, IL; Karin I. Armstrong, United Hospital, Woodbury, MN; Nassim H. Nabbout, Cancer Center of Kansas, Wichita, KS; Bassel F. El-Rayes, Emory University, Atlanta, GA; Adedayo A. Onitilo, Marshfield Clinic, Marshfield, WI; Daniel J. Moriarty, Overlook Medical Center, Summit, NJ; and Thomas J. Fitzgerald, Imaging and Radiation Oncology Core, Quality Assurance Review Center, Providence, RI.
authors.forename: Al B
authors.initials: AB
authors.lastname: Benson
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001005:Anus Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy*; D000068818:Cetuximab / Q000008:administration & dosage; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007121:Immunocompetence; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015996:Survival Rate
chemical_list: D000068818:Cetuximab; D002945:Cisplatin; D005472:Fluorouracil