Cetuximab plus chemoradiotherapy for HIV-associated anal carcinoma

A phase II AIDS malignancy consortium trial

Joseph A. Sparano, Jeannette Y. Lee, Joel Palefsky, David H. Henry, William Wachsman, Lakshmi Rajdev, David Aboulafia, Lee Ratner, Thomas J. Fitzgerald, Lisa Kachnic, Ronald Mitsuyasu

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 a, 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.

Original languageEnglish (US)
Pages (from-to)727-733
Number of pages7
JournalJournal of Clinical Oncology
Volume35
Issue number7
DOIs
StatePublished - Mar 1 2017

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Anal Canal
Chemoradiotherapy
Papillomaviridae
Squamous Cell Carcinoma
Acquired Immunodeficiency Syndrome
HIV
Carcinoma
Kaplan-Meier Estimate
HIV Infections
Neoplasms
Radiotherapy
Radiation Dosage
Poisons
Fluorouracil
Cisplatin
Disease-Free Survival
Lymph Nodes
Recurrence
Survival
Cetuximab

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Cetuximab plus chemoradiotherapy for HIV-associated anal carcinoma : A phase II AIDS malignancy consortium trial. / Sparano, Joseph A.; Lee, Jeannette Y.; Palefsky, Joel; Henry, David H.; Wachsman, William; Rajdev, Lakshmi; Aboulafia, David; Ratner, Lee; Fitzgerald, Thomas J.; Kachnic, Lisa; Mitsuyasu, Ronald.

In: Journal of Clinical Oncology, Vol. 35, No. 7, 01.03.2017, p. 727-733.

Research output: Contribution to journalArticle

Sparano, JA, Lee, JY, Palefsky, J, Henry, DH, Wachsman, W, Rajdev, L, Aboulafia, D, Ratner, L, Fitzgerald, TJ, Kachnic, L & Mitsuyasu, R 2017, 'Cetuximab plus chemoradiotherapy for HIV-associated anal carcinoma: A phase II AIDS malignancy consortium trial', Journal of Clinical Oncology, vol. 35, no. 7, pp. 727-733. https://doi.org/10.1200/JCO.2016.69.1642
Sparano, Joseph A. ; Lee, Jeannette Y. ; Palefsky, Joel ; Henry, David H. ; Wachsman, William ; Rajdev, Lakshmi ; Aboulafia, David ; Ratner, Lee ; Fitzgerald, Thomas J. ; Kachnic, Lisa ; Mitsuyasu, Ronald. / Cetuximab plus chemoradiotherapy for HIV-associated anal carcinoma : A phase II AIDS malignancy consortium trial. In: Journal of Clinical Oncology. 2017 ; Vol. 35, No. 7. pp. 727-733.
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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 a, 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.",
author = "Sparano, {Joseph A.} and Lee, {Jeannette Y.} and Joel Palefsky and Henry, {David H.} and William Wachsman and Lakshmi Rajdev and David Aboulafia and Lee Ratner and Fitzgerald, {Thomas J.} and Lisa Kachnic and Ronald Mitsuyasu",
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T1 - Cetuximab plus chemoradiotherapy for HIV-associated anal carcinoma

T2 - A phase II AIDS malignancy consortium trial

AU - Sparano, Joseph A.

AU - Lee, Jeannette Y.

AU - Palefsky, Joel

AU - Henry, David H.

AU - Wachsman, William

AU - Rajdev, Lakshmi

AU - Aboulafia, David

AU - Ratner, Lee

AU - Fitzgerald, Thomas J.

AU - Kachnic, Lisa

AU - Mitsuyasu, Ronald

PY - 2017/3/1

Y1 - 2017/3/1

N2 - 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 a, 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.

AB - 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 a, 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.

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