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 |