Phase I study of induction chemotherapy with afatinib, ribavirin, and weekly carboplatin and paclitaxel for stage IVA/IVB human papillomavirus-associated oropharyngeal squamous cell cancer Journal Article


Authors: Dunn, L. A.; Fury, M. G.; Sherman, E. J.; Ho, A. A.; Katabi, N.; Haque, S. S.; Pfister, D. G.
Article Title: Phase I study of induction chemotherapy with afatinib, ribavirin, and weekly carboplatin and paclitaxel for stage IVA/IVB human papillomavirus-associated oropharyngeal squamous cell cancer
Abstract: Background: The human papillomavirus (HPV) E6 oncoprotein enhances the oncogenic potential of ErbB proteins in HPV-related malignancies. This phase I study evaluates the addition of afatinib, an ErbB family inhibitor, and ribavirin to paclitaxel and carboplatin induction chemotherapy in HPV-associated, locally advanced oropharyngeal squamous cell carcinoma (SCC). Methods: This dose escalation study included 2 doses of oral afatinib: 30 and 40 mg daily. Ribavirin dosing was weight based. Paclitaxel (80 mg/m2) and carboplatin (area under the curve [AUC] 1.5) were administered on days 1 and 8 of each 21-day cycle. After 3 cycles, patients were removed from protocol to receive definitive treatment. Results: Among 10 patients, there were no dose-limiting toxicities. Six patients (67%) had unconfirmed objective partial responses. The 2-year progression-free survival rate was 75%. Conclusion: Afatinib, ribavirin, paclitaxel, and carboplatin induction chemotherapy is safe and well tolerated. The phase II recommended dose of afatinib is 40 mg oral daily in this combination regimen. © 2017 Wiley Periodicals, Inc.
Keywords: immunohistochemistry; adult; cancer survival; clinical article; treatment response; aged; drug tolerability; fatigue; squamous cell carcinoma; area under the curve; diarrhea; drug efficacy; drug safety; hypertension; recommended drug dose; side effect; paclitaxel; cancer staging; anorexia; disease association; carboplatin; progression free survival; multiple cycle treatment; pain; anemia; mucosa inflammation; nausea; vomiting; clinical assessment; dizziness; drug dose escalation; dyspnea; flushing; pruritus; rash; hypoxia; in situ hybridization; bilirubin; hypoalbuminemia; hypotension; thorax pain; karnofsky performance status; laboratory test; evening dosage; morning dosage; phase 1 clinical trial; dyspepsia; alopecia; epistaxis; bilirubin blood level; ribavirin; induction chemotherapy; hypocalcemia; sinus tachycardia; human papillomavirus; papillomavirus infection; oropharyngeal cancer; body weight loss; afatinib; faintness; human; male; female; priority journal; article; oropharynx squamous cell carcinoma
Journal Title: Head & Neck
Volume: 40
Issue: 2
ISSN: 1043-3074
Publisher: John Wiley & Sons, Inc.  
Date Published: 2018-02-01
Start Page: 233
End Page: 241
Language: English
DOI: 10.1002/hed.24938
PROVIDER: scopus
PUBMED: 28963790
PMCID: PMC6760238
DOI/URL:
Notes: Article -- Export Date: 6 February 2018 -- Source: Scopus
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MSK Authors
  1. Eric J Sherman
    303 Sherman
  2. Sofia S Haque
    139 Haque
  3. Nora Katabi
    282 Katabi
  4. David G Pfister
    366 Pfister
  5. Matthew G Fury
    102 Fury
  6. Alan Loh Ho
    209 Ho
  7. Lara   Dunn
    118 Dunn