Integration of gefitinib (G), into a concurrent chemoradiation (CRT) regimen followed by G adjuvant therapy in patients with locally advanced head and neck cancer (HNC) - a Phase II Trial

Abstract

5506 Background: This study was undertaken to evaluate the tolerability and efficacy of substituting G for paclitaxel into a well-described CRT regimen (Clin Cancer Res 9: 5936; JCO 21: 320) and then continuing G as adjuvant therapy. Endpoints included complete response (CR) rate to CRT, progression-free and overall survival, and local and distant control rates. Methods: Previously untreated subjects with stage III, IVa, or IVb HNC were enrolled and were required to have squamous cell or poorly differentiated carcinomas, or lymphoepithelioma. Organ sparing prior surgical therapy was allowed. Subjects received 2 cycles of induction chemotherapy (carboplatin and paclitaxel) followed by CRT consisting of G (250mg PO OD), 5FU, hydroxyurea, and twice daily radiation on a week on/week off schedule repeated every 14 days. G (250mg PO OD) was continued for at total of 2 years from the start of CRT. Results: From 2/03 to 10/04, 69 subjects were accrued. Characteristics included 52 males; median age 55; ECOG performance status 0 in 49, 1 in 19, and 2 in 1; and stage IV disease in 63 (91%). With a current median follow-up of 294 days and 42 subjects evaluable for response to CRT we have observed 37 CR (88%). Non-evaluable subjects withdrew consent and never received G (3), underwent surgery prior to CRT (6), expired prior to evaluation (2), or have not yet been evaluated (16). Thus far there have been 2 subjects with progressive disease (1 distant and 1 local) and four deaths (1 disease progression, 1 Listeria sepsis, 1 cardiac failure, 1 post-op complication). Grade 3 and 4 toxicity has been consistent with previous CRT or single-agent G trials, including mucositis (73% and 10%), radiation dermatitis (29% and 2%), pustulo-papular rash (6% and 0%), and diarrhea (2% and 0%). 80% of eligible subjects continue to adhere to maintenance G therapy. Conclusions: The addition of G to concurrent CRT after induction chemotherapy and its administration as adjuvant therapy appears tolerable and feasible. High rates of CR and few recurrences seen thus far suggest that this is a promising regimen for patients with locally advanced HNC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer AstraZeneca, Bristol-Myers Squibb