Accelerated Weekly Concomitant Boost Postoperative Radiation Therapy Combined to Concomitant Chemotherapy in Patients With Locally Advanced Head and Neck Cancer

Accelerated Weekly Concomitant Boost Postoperative Radiation Therapy Combined to Concomitant Chemotherapy in Patients With Locally Advanced Head and Neck Cancer

I. J. Radiation Oncology d Biology d Physics S428 2404 Volume 69, Number 3, Supplement, 2007 Accelerated Weekly Concomitant Boost Postoperative Ra...

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I. J. Radiation Oncology d Biology d Physics

S428

2404

Volume 69, Number 3, Supplement, 2007

Accelerated Weekly Concomitant Boost Postoperative Radiation Therapy Combined to Concomitant Chemotherapy in Patients With Locally Advanced Head and Neck Cancer

B. Pehlivan, A. Zouhair, O. Matzinger, F. Luthi, L. Bron, P. Pasche, W. Seelentag, S. Bulling, R. O. Mirimanoff, M. Ozsahin University Hospital Center and University of Lausanne, Lausanne, Switzerland Purpose/Objective(s): To assess the feasibility and efficacy of accelerated weekly 6 fractionated 66-Gy postoperative radiation therapy (PORT) using a single fraction regimen from Monday to Thursday and a concomitant boost in the Friday afternoon sessions combined with concomitant cisplatin chemotherapy (CT) in patients with locally-advanced head and neck cancer (LAHNC). Materials/Methods: Between March 2001 and April 2006, 40 (male to female ratio: 35/5; median age: 60 years [range: 36– 81]) patients with pT1-pT4 and/or pN0-pN3 LAHNC (15 oral cavity, 8 oropharynx, 8 hypopharynx, 7 larynx, and 2 unknown primary) were included in this pilot study. Indications of PORT/CT were positive surgical margins (n = 9; all R1), T4 R0 tumors (n = 5), 3 or more positive lymph nodes without extranodal infiltration (all R0; n = 2) in 16 (40%) patients; or extranodal infiltration with (all R1; n = 13) or without (n = 11) positive surgical margins in 24 (60%) patients. Median interval between surgery and RT was 46 days (range: 24–112). RT consisted of 66 Gy (2 Gy/fr) in 5.5 weeks. Median RT duration was 39 days (range: 35–62). Five-field 3D conformal or intensity-modulated RT was performed in all patients according to the GORTEC/EORTC/RTOG guidelines. Concomitant cisplatin chemotherapy was planned at 100 mg/m2 in days 1, 22, and 43 in all but one patient where carboplatin was chosen due to impaired renal function. Prophylactic percutaneous endoscopic gastrostomy was performed in 18 (45%) patients, and 3 (8%) patients required nasogastric feeding tube. Median follow-up was 37 months (range: 5–66). Results: All but two patients received the planned total dose without unplanned interruption (66 Gy in 38, 64 Gy in 1, and 58 Gy in 1). According to the CTC/NCI v3.0 toxicity criteria, acute morbidity was acceptable: grade 3 mucositis in 10 (25%), grade 3 dysphagia in 9 (23%), grade 3 skin erythema in 5 (13%) patients. CT-related anemia was observed in 2 patients (grade 3 in 1, and grade 4 in 1), leukopenia in 4 patients (grade 3 in 2, and grade 4 in 2), and no grade 3 or 4 thrombocytopenia was observed. Grade 3 renal-function impairment was observed only in one patient. Median weight loss was 3.5 kg (range: 0–14.5). No treatmentrelated mortality was observed. Considering the late effects, grade 0, 1, or 2 xerostomia was observed in 9 (23%), 22 (55%), and 9 (23%) patients, respectively; grade 0, 1, and 2 edema in 25 (63%), 14 (35%), and 1 (3%) patients, respectively. Locoregional relapse was observed in 8 (20%) patients, and only 7 (18%) patients developed distant metastases. Median time to locoregional relapse was 6 months (range: 1–40). The 3-year overall, cause-specific, disease-free survival, and locoregional control rates were 65%, 69%, 64%, and 82%, respectively. Distant metastasis probability at 3 and 5 years was 19%. Univariate and multivariate analyses revealed that the only prognostic factor influencing the outcome was nodal status. Conclusions: We conclude that reducing the overall treatment time using accelerated PORT/CT by weekly concomitant boost (6 fractions per week) combined to concomitant cisplatin chemotherapy is easily feasible with good locoregional and distant metastases control for patients operated with curative intent for LAHNC. Acute and late RT/CT-related morbidity is acceptable. Author Disclosure: B. Pehlivan, None; A. Zouhair, None; O. Matzinger, None; F. Luthi, None; L. Bron, None; P. Pasche, None; W. Seelentag, None; S. Bulling, None; R.O. Mirimanoff, None; M. Ozsahin, None.

2405

Phase I/II Study of Concurrent Erlotinib and Chemoradiation for Post-Resected Locally Advanced Squamous Head and Neck Cancer (HNSCC): A Gicor Study

F. Arias de la Vega1, I. Herruzo2, M. de las Heras3, A. de la Torre4, L. del Rı´o1, J. Contreras2, I. Prieto5, J. A. Garcı´a Saenz3, M. L. Amador6, F. A. Calvo5 Hospital de Navarra, Pamplona, Spain, 2Hospital Carlos Haya, Ma´laga, Spain, 3Hospital Clı´nico San Carlos, Madrid, Spain, Hospital Universitario Puerta de Hierro, Madrid, Spain, 5Hospital Universitario Gregorio Maran˜o´n, Madrid, Spain, 6Roche Farma, Madrid, Spain 1

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Purpose/Objective(s): Concurrent chemoradiation is considered the optimal treatment for advanced HNSCC, including post-resected status. Erlotinib (TarcevaÒ) is an oral EGFR TKI, with activity in recurrent and metastatic HNSCC. The Spanish Group of Clinical Research in Radiation Oncology (GICOR) leads a phase I/II study to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of adding erlotinib (e) to chemoradiation to patients (p) with surgically resected locally advanced HNSCC. Materials/Methods: p had surgically resected advanced HNSCC, with a least one of the following criteria: T3 or T4 primary lesion (except T3N0 with negative resection margins), pathologic N2-N3 disease, and poor prognostic findings (i.e. extranodal spread, positive resection margins, perineural or perivascular involvement). Additional eligibility criteria included: age 18–70 y; life expectancy $12 w; PS 0-1; no evidence of metastasis; adequate organic function; and written informed consent. Dose-escalating phase I study consisted on 3 cohorts of 3–6 p each, with increasing doses of erlotinib (100–150 mg po qd) and cisplatin (30–40 mg/m2, iv, d 1) for 7 w. Radiotherapy was delivered as a fixed standard regimen of daily 1.8 Gy (5 fractions/w) to a total dose of 63 Gy in high risk areas along 7 w. Results: By the time of this analysis, 7 p have entered the phase I component of the study. Median age: 52 y; male 100%. Complete data for 4 pats included in cohort 1 (e 100 mg/d, c 30 mg/m2) are available. One p withdrew prematurely the study due to a grade 2 toxicity (not considered DLT) and was considered unevaluable by the Scientific Committee. Among evaluable p, 2 developed mucositis (1 g.3), vomiting (g.1) and nausea (g.1). All p developed skin rash (mild in all the cases). Haematological toxicities were single cases of anaemia, leukopenia and thrombocytopenia (g.1). All 3 p completed 7 weeks of treatment and no dose reduction was required. No DLT as per protocol has been described and study went subsequently further to cohort 2. Conclusions: This study demonstrates the safe addition of erlotinib to chemoradiotherapy in the treatment of this p population. Full data from the phase I study will be presented. Author Disclosure: F. Arias de la Vega, None; I. Herruzo, None; M. de las Heras, None; A. de la Torre, None; L. del Rı´o, None; J. Contreras, None; I. Prieto, None; J.A. Garcı´a Saenz, None; M.L. Amador, Roche Farma, A. Employment; F.A. Calvo, None.