title: Cetuximab Plus Chemoradiotherapy for HIV-Associated Anal Carcinoma: A Phase II AIDS Malignancy Consortium Trial.
abstract: Purpose Squamous cell carcinoma of the anal canal (SCCAC) is characterized by high locoregional failure (LRF) rates after definitive chemoradiation (CRT), associated with anogenital human papilloma virus, and often appears in HIV infection. Because cetuximab enhances the effect of radiation therapy in human papilloma virus-associated oropharyngeal SCC, we hypothesized that adding cetuximab to CRT would reduce LRF in SCCAC. Methods Forty-five patients with stage I to III SCCAC and HIV infection received CRT: 45 to 54 Gy radiation therapy to the primary tumor and regional lymph nodes plus eight once-weekly doses of concurrent cetuximab and two cycles of cisplatin and fluorouracil. 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 The 3-year LRF rate was 42% (95% CI, 28% to 56%; one-sided P = .9) by binomial proportional estimate using the prespecified end point (LRF or alive without LRF and followed < 3 years), and 20% (95% CI, 10% to 37%) by Kaplan-Meier estimate in post hoc analysis using definitions and methods consistent with historical data. Three-year rates by Kaplan-Meier estimate were 72% (95% CI, 56% to 84%) for progression-free survival and 79% (95% CI, 63% to 89%) for overall survival. Grade 4 toxicity occurred in 26%, and 4% had treatment-associated deaths. Conclusion HIV-associated SCCAC is potentially curable with definitive CRT. Although addition of cetuximab may result in less LRF, the 20% recurrence and 26% grade 4 toxicity rates indicate the continued need for more-effective and less-toxic therapies.
authors.affiliation: Joseph A. Sparano and Lakshmi Rajdev, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Jeannette Y. Lee, University of Arkansas for Medical Sciences, Little Rock, AR; Joel Palefsky, University of California San Francisco, San Francisco; William Wachsman, University of California San Diego, San Diego; Ronald Mitsuyasu, University of California Los Angeles, Los Angeles, CA; David H. Henry, University of Pennsylvania, Philadelphia, PA; David Aboulafia, Virginia Mason Medical Center, Seattle, WA; Lee Ratner, Washington University, St Louis, MO; Thomas J. Fitzgerald, Quality Assurance Review Center, Providence, RI; and Lisa Kachnic, Boston University Medical Center, Boston, MA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Sparano
authors.affiliation: Joseph A. Sparano and Lakshmi Rajdev, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Jeannette Y. Lee, University of Arkansas for Medical Sciences, Little Rock, AR; Joel Palefsky, University of California San Francisco, San Francisco; William Wachsman, University of California San Diego, San Diego; Ronald Mitsuyasu, University of California Los Angeles, Los Angeles, CA; David H. Henry, University of Pennsylvania, Philadelphia, PA; David Aboulafia, Virginia Mason Medical Center, Seattle, WA; Lee Ratner, Washington University, St Louis, MO; Thomas J. Fitzgerald, Quality Assurance Review Center, Providence, RI; and Lisa Kachnic, Boston University Medical Center, Boston, MA.
authors.forename: Jeannette Y
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Joseph A. Sparano and Lakshmi Rajdev, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Jeannette Y. Lee, University of Arkansas for Medical Sciences, Little Rock, AR; Joel Palefsky, University of California San Francisco, San Francisco; William Wachsman, University of California San Diego, San Diego; Ronald Mitsuyasu, University of California Los Angeles, Los Angeles, CA; David H. Henry, University of Pennsylvania, Philadelphia, PA; David Aboulafia, Virginia Mason Medical Center, Seattle, WA; Lee Ratner, Washington University, St Louis, MO; Thomas J. Fitzgerald, Quality Assurance Review Center, Providence, RI; and Lisa Kachnic, Boston University Medical Center, Boston, MA.
authors.forename: Joel
authors.initials: J
authors.lastname: Palefsky
authors.affiliation: Joseph A. Sparano and Lakshmi Rajdev, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Jeannette Y. Lee, University of Arkansas for Medical Sciences, Little Rock, AR; Joel Palefsky, University of California San Francisco, San Francisco; William Wachsman, University of California San Diego, San Diego; Ronald Mitsuyasu, University of California Los Angeles, Los Angeles, CA; David H. Henry, University of Pennsylvania, Philadelphia, PA; David Aboulafia, Virginia Mason Medical Center, Seattle, WA; Lee Ratner, Washington University, St Louis, MO; Thomas J. Fitzgerald, Quality Assurance Review Center, Providence, RI; and Lisa Kachnic, Boston University Medical Center, Boston, MA.
authors.forename: David H
authors.initials: DH
authors.lastname: Henry
authors.affiliation: Joseph A. Sparano and Lakshmi Rajdev, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Jeannette Y. Lee, University of Arkansas for Medical Sciences, Little Rock, AR; Joel Palefsky, University of California San Francisco, San Francisco; William Wachsman, University of California San Diego, San Diego; Ronald Mitsuyasu, University of California Los Angeles, Los Angeles, CA; David H. Henry, University of Pennsylvania, Philadelphia, PA; David Aboulafia, Virginia Mason Medical Center, Seattle, WA; Lee Ratner, Washington University, St Louis, MO; Thomas J. Fitzgerald, Quality Assurance Review Center, Providence, RI; and Lisa Kachnic, Boston University Medical Center, Boston, MA.
authors.forename: William
authors.initials: W
authors.lastname: Wachsman
authors.affiliation: Joseph A. Sparano and Lakshmi Rajdev, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Jeannette Y. Lee, University of Arkansas for Medical Sciences, Little Rock, AR; Joel Palefsky, University of California San Francisco, San Francisco; William Wachsman, University of California San Diego, San Diego; Ronald Mitsuyasu, University of California Los Angeles, Los Angeles, CA; David H. Henry, University of Pennsylvania, Philadelphia, PA; David Aboulafia, Virginia Mason Medical Center, Seattle, WA; Lee Ratner, Washington University, St Louis, MO; Thomas J. Fitzgerald, Quality Assurance Review Center, Providence, RI; and Lisa Kachnic, Boston University Medical Center, Boston, MA.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Rajdev
authors.affiliation: Joseph A. Sparano and Lakshmi Rajdev, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Jeannette Y. Lee, University of Arkansas for Medical Sciences, Little Rock, AR; Joel Palefsky, University of California San Francisco, San Francisco; William Wachsman, University of California San Diego, San Diego; Ronald Mitsuyasu, University of California Los Angeles, Los Angeles, CA; David H. Henry, University of Pennsylvania, Philadelphia, PA; David Aboulafia, Virginia Mason Medical Center, Seattle, WA; Lee Ratner, Washington University, St Louis, MO; Thomas J. Fitzgerald, Quality Assurance Review Center, Providence, RI; and Lisa Kachnic, Boston University Medical Center, Boston, MA.
authors.forename: David
authors.initials: D
authors.lastname: Aboulafia
authors.affiliation: Joseph A. Sparano and Lakshmi Rajdev, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Jeannette Y. Lee, University of Arkansas for Medical Sciences, Little Rock, AR; Joel Palefsky, University of California San Francisco, San Francisco; William Wachsman, University of California San Diego, San Diego; Ronald Mitsuyasu, University of California Los Angeles, Los Angeles, CA; David H. Henry, University of Pennsylvania, Philadelphia, PA; David Aboulafia, Virginia Mason Medical Center, Seattle, WA; Lee Ratner, Washington University, St Louis, MO; Thomas J. Fitzgerald, Quality Assurance Review Center, Providence, RI; and Lisa Kachnic, Boston University Medical Center, Boston, MA.
authors.forename: Lee
authors.initials: L
authors.lastname: Ratner
authors.affiliation: Joseph A. Sparano and Lakshmi Rajdev, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Jeannette Y. Lee, University of Arkansas for Medical Sciences, Little Rock, AR; Joel Palefsky, University of California San Francisco, San Francisco; William Wachsman, University of California San Diego, San Diego; Ronald Mitsuyasu, University of California Los Angeles, Los Angeles, CA; David H. Henry, University of Pennsylvania, Philadelphia, PA; David Aboulafia, Virginia Mason Medical Center, Seattle, WA; Lee Ratner, Washington University, St Louis, MO; Thomas J. Fitzgerald, Quality Assurance Review Center, Providence, RI; and Lisa Kachnic, Boston University Medical Center, Boston, MA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Fitzgerald
authors.affiliation: Joseph A. Sparano and Lakshmi Rajdev, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Jeannette Y. Lee, University of Arkansas for Medical Sciences, Little Rock, AR; Joel Palefsky, University of California San Francisco, San Francisco; William Wachsman, University of California San Diego, San Diego; Ronald Mitsuyasu, University of California Los Angeles, Los Angeles, CA; David H. Henry, University of Pennsylvania, Philadelphia, PA; David Aboulafia, Virginia Mason Medical Center, Seattle, WA; Lee Ratner, Washington University, St Louis, MO; Thomas J. Fitzgerald, Quality Assurance Review Center, Providence, RI; and Lisa Kachnic, Boston University Medical Center, Boston, MA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Kachnic
authors.affiliation: Joseph A. Sparano and Lakshmi Rajdev, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Jeannette Y. Lee, University of Arkansas for Medical Sciences, Little Rock, AR; Joel Palefsky, University of California San Francisco, San Francisco; William Wachsman, University of California San Diego, San Diego; Ronald Mitsuyasu, University of California Los Angeles, Los Angeles, CA; David H. Henry, University of Pennsylvania, Philadelphia, PA; David Aboulafia, Virginia Mason Medical Center, Seattle, WA; Lee Ratner, Washington University, St Louis, MO; Thomas J. Fitzgerald, Quality Assurance Review Center, Providence, RI; and Lisa Kachnic, Boston University Medical Center, Boston, MA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Mitsuyasu
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001005:Anus Neoplasms / Q000473:pathology / Q000628:therapy* / Q000821:virology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy* / Q000821:virology*; D000068818:Cetuximab / Q000008:administration & dosage; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015658:HIV Infections / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000068818:Cetuximab; D002945:Cisplatin; D005472:Fluorouracil