The cytoprotective effect of amifostine in concomitant chemoradiotherapy of locally advanced non-small cell lung cancer

Purpose: Chemoradiotherapy (CT-RT) with dose escalation is an effective treatment for LA-NSCLC. This management can be limited by acute and late toxicities, especially radiation pneumonitis (RP) and acute esophagitis (AE). Cytoprotection by amifostine could reduce the incidence of induced acute and late toxicities.

Methods: Between 2000 and 2006, a total of 32 patients with LA-NSCLC stage IIIA and IIIB were treated. All patients were randomized to treatment with neoadjuvant chemotherapy (4 cycles) followed by concomitant CT-RT (2 cycles) plus amifostine (500 mg daily i.v. infusion) – group A (n=16) and without amifostine – group B (n=16). Chemotherapy consisted of paclitaxel (175 mg/m² i.v. infusion) day 1 and cisplatin (75 mg/m ² i.v. infusion) day 1 (during the concomitant CT-RT day 2), administered every 3 weeks. All patients were treated using 3D conformal radiotherapy (3D-CRT). All patients were assessed at each follow-up visit for signs and symptoms of RP and AE according to the Common Toxicity Criteria - version 2.0. Lung tissue had been sampled from two different sites. In both patient groups, the first sample came from the area of PTV 2 (A_max , B_max) while the second sample was taken from the intact lung outside the PTV 1 (A _ref , B _ref ).

Results: Median 3D-CRT dose was 67.4 Gy (63.8 - 72.8 Gy) with planning doses to the ICRU reference point. Symptoms of RP grade 3/4 and AE grade 3/4 occurred in 4 and 3 patients in group A vs. 8 and 7 patients in group B. Differences were statistically significant (p=0.001). Median thickness of the alveolocapillary space was 8.4 µm (range 2.1-11.2) and 3.1 µm (range 0.9-4.2) for the A_max and A_ref samples compared to 49.3 µm (range 10.2-71.4) and 2.8 µm (range 1.1-3.8) for the B_max and B_ref samples, respectively. The difference between A_max and B_max samples was statistically significant (p=0.0001).

Conclusions: The incidence of pneumonitis and esophagitis was lower for patients receiving amifostine than for patients receiving chemoradiotherapy alone. Significant differences of the thickness of alveolocapillary space may represent the cytoprotective effect of amifostine.

Disclosure: All authors have declared no conflicts of interest.