Low-dose radiotherapy as a chemo-potentiator of a chemotherapy regimen with pemetrexed for recurrent non-small-cell lung cancer: a prospective phase II study.

Low-dose radiotherapy (LDR) (<50 cGy) induces enhanced cell killing in vitro via the hyper-radiation sensitivity phenomenon. Aim of this study was to evaluate the safety and efficacy of a palliative regimen combining pemetrexed and LDR (as a chemopotentiator) on patients affected by recurrent non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Eligible patients had an ECOG performance status ≤2, one prior chemotherapy regimen for advanced NSCLC, adequate organ function, measurable lesions. Patients received pemetrexed (500 mg/m(2) IV) and concurrent LDR (40 cGy bid on days 1 and 2) delivered to target pulmonary or metastatic disease. This cycle was repeated fourfold every 21 days. The accrual was determined by the single proportion powered analysis (α=0.05, power=0.8) with H0 ("bad" response probability, 9% according to literature) and H1 ("good" response probability, 35% ongoing study); 19 is the number required. RESULTS: Nineteen patients with stage III and IV disease were enrolled. Only one patient experienced neutropenia grade 4. All patients are evaluable for clinical response of irradiated lesion: overall response rate was 42%. CONCLUSIONS: Low-dose radiotherapy combined with pemetrexed has a similar toxicity profile to chemotherapy alone. The response rate of this novel approach is encouraging, since it was higher than what was reported for pemetrexed alone (42% versus 9.1%). Additional scientific investigation of this new treatment paradigm is warranted.