Concurrent chemo-irradiation using accelerated concomitant boost radiation therapy in loco-regionally advanced head...

To investigate the feasibility of combining concomitant boost-accelerated radiation regimen (ACB) with full-dose mono-chemotherapy using cisplatin and to assess its local response and acute toxicity patterns in patients with advanced loco-regional head and neck squamous cell carcinoma (HNSCC).

Between July 2004 and August 2005, a pilot study involving 27 patients with stage III to IVB (AJCC-6th) HNSCC of the oropharynx, hypopharynx and larynx who met the eligibility criteria was undertaken. Twenty-four of these patients (median age--53 years) were analyzable. The radiation dose was 72 Gy in 42 fractions over 6 weeks, delivered in one daily fraction of 1.8 Gy during the first 3.5 weeks and two fractions per day, 1.8 Gy and 1.5 Gy boost-separated by > 6 h interval, during the last 2.5 weeks. cisplatin, 100 mg/m2, was given in intravenous (i.v.) infusion on day 1 and day 22. Tumor and clinical status were assessed and acute toxicities were graded.

Out of 27 patients, 24 patients received both radiation and chemotherapy as per protocol and were available for analysis. The loco-regional response rates were as follows: an overall response of 95.8% (23 patients), a complete response of 79.1% (19 patients), a partial response of 16.7% (4 patients) and progressive disease in 4.2% (1 patient). Dysphagia, nausea, vomiting and bone marrow suppression were the most common side effects and were associated with cisplatin administration. One patient (3.7%) died of complications (pneumonia and sepsis), 3 patients (12.5%) had acute grade 4 toxicity and 21 patients (87.5%) had acute grade 3 (17 patients) or grade 2 (4 patients) toxicity.

This data shows that it is feasible to combine ACB and full-dose mono-chemotherapy using cisplatin with manageable, although substantial, toxicity. The compliance to therapy was high and the loco-regional response achieved compared favorably with ACB alone or other concurrent chemoradiation regimens using standard or altered fractionation regimens tested by the Institute. It also compares well with the available literature. An extended phase II trial; and a new phase III trial, comparing ACB plus cisplatin against standard radiation plus cisplatin, are being planned at the Institute to determine whether the use of ACB in the concurrent chemoradiation setting further improves outcome.