Combined modality therapy with radiation therapy (RT), chemotherapy, bevacizumab, and erlotinib in the treatment of patients (pts) with locally advanced squamous carcinoma of the head and neck

Abstract

6012 Background: Concurrent chemotherapy/RT is the standard of treatment for locally advanced head and neck cancer. Agents targeting EGFR and the angiogenesis pathway have also demonstrated activity. In this phase II trial, we added bevacizumab and erlotinib to an active combined modality regimen in the first-line treatment of pts with locally advanced head and neck cancer. Methods: Eligible pts had previously untreated squamous carcinoma of any head and neck site, with T3/T4 primary lesions and/or N1-N3 nodal involvement. Additional eligibility: ECOG PS 0 or 1; adequate organ function; indwelling central venous catheter; standard bevacizumab exclusions. All pts received induction therapy with 2 courses of paclitaxel (200mg/m2), carboplatin (AUC 6.0), 5-FU (200mg/m2 per day, 24 hour CI days 1–21), and bevacizumab (15 mg/kg); cycles were repeated at 21-day intervals. Pts then received concurrent RT (68.4 Gy, 1.8 Gy/day), paclitaxel (50 mg/m2 weekly x 6), bevacizumab (15 mg/kg weeks 1 and 4), and erlotinib (150 mg daily x 7 weeks). PFS was the primary endpoint. Results: Between December 2006 and July 2008, 60 pts were enrolled; the first 48 pts are included in this preliminary report. The median age was 56 years; T3/T4 = 9/8; N1/N2/N3 = 13/27/4. 45 pts (94%) completed the 6-week induction therapy, and 41 pts (85%) completed all therapy. After induction therapy, 56% of pts had objective response; 77% had objective response after completion of therapy. After a median follow-up of 16 months, the 18-month progression-free and overall survivals are 85% and 87%, respectively. Grade 3/4 toxicity during induction therapy included neutropenia (46%), neutropenic fever (6%), mucositis (14%), diarrhea (14%), and hand/foot syndrome (11%). Severe local toxicity (mucositis/esophagitis) occurred in 31 patients (76%) during combined modality therapy (56% grade 3/20% grade 4). Conclusions: The addition of bevacizumab and erlotinib to concurrent chemotherapy/RT was feasible, with no unexpected toxicity. After short followup, the regimen appears highly active. Updated results will be presented. [Table: see text]

Angiogenesis in Head and Neck Cancer: A Review of the Literature

“…Patients with no prior radiation had a significantly longer OS (40.1 months) than those previously irradiated (10.3 months). This study demonstrates that bevacizumab 10 mg/kg every two weeks can be safely integrated to fluorouracil and hydroxyurea-based concomitant chemoradiotherapy: the rate of severe complication was similar to those reported in trials with different agents in cohorts of patients with the same characteristics [ 55 – 68 ].…”

“…Sorafenib [ 45 , 46 ] did not give encouraging results with regard to objective response but interesting data of PFS and OS when used as first-line treatment. Few studies have just been concluded and published in patients with locoregionally advanced disease [ 67 , 68 ], and the results of these trials have to be confirmed with a longer followup.…”

“…In the first trial [ 68 ] the authors treated 60 patients with newly diagnosed locoregionally advanced HNSCC with two courses of induction chemotherapy repeated every 21 days consisting of carboplatin AUC 6 day 1, paclitaxel 200 mg/mq day 1, 5 fluorouracil 200 mg/mq/day continuous infusion every 3 weeks, and bevacizumab 15 mg/kg day 1 followed by radiotherapy and concomitant paclitaxel 50 mg/mq/weekly, bevacizumab 15 mg/kg weeks 1 and 4, and erlotinib 150 mg daily for 7 weeks. Forty-one patients (85%) completed all treatments with an objective response rate of 77%.…”