Friday, July 9, 2010

JCO: Gefitinib integration into CTRT for H&N cancer

JCO this week:

An interesting phase II looking at the integration of gefitinib (an EGFR TKI), with concurrent chemoradiotherapy. The overall approach is different than what many centers would call standard treatment with induction carbo/paclitaxel, followed by 5FU, HU, and gefinitib with BID RT, then continuing gefitinib afterwards. The results however are good in comparison to historical controls, and it will be very interesting to see how integration of EGFR inhibition in ongoing phase III trials will fair when result mature over the next ~5 years.

Link and abstract

Epidermal Growth Factor Receptor Inhibitor Gefitinib Added to Chemoradiotherapy in Locally Advanced Head and Neck Cancer [Head and Neck Cancer]: "Purpose

Assess efficacy and toxicity of gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, added to, and in maintenance after, concurrent chemoradiotherapy (CCRT) in locally advanced head and neck cancer (LA-HNC) and correlate outcomes with EGFR gene copy number alterations.

Patients and Methods

Patients with stage III to IV LA-HNC received two cycles of carboplatin/paclitaxel induction chemotherapy (IC) followed by split-course CCRT with fluorouracil, hydroxyurea, twice daily radiotherapy (FHX), and gefitinib (250 mg daily) followed by continued gefitinib for 2 years total. The primary end point was complete response (CR) rate after CCRT. EGFR gene copy number was assessed by fluorescent in situ hybridization.


Sixty-nine patients (66 with stage IV disease, 37 with oropharynx primary tumors, and 67 with performance status 0 to 1) were enrolled with a median age of 55 years. Predominant grade 3 or 4 toxicities during IC and CCRT were neutropenia (n = 20) and in-field mucositis (n = 59) and dermatitis (n = 23), respectively. CR rate after CCRT was 90%. After median follow-up of 3.5 years, 4-year overall, progression-free, and disease-specific survival rates were 74%, 72%, and 89%, respectively. To date, one patient has developed a second primary tumor in the aerodigestive tract. In 31 patients with available tissue, high EGFR gene copy number was associated with worse overall survival (P = .02).


Gefitinib can be administered with FHX and as maintenance therapy for at least 2 years, demonstrating CR and survival rates that compare favorably with prior experience. High EGFR gene copy number may be associated with poor outcome in patients with LA-HNC treated with this regimen.


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