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

Radiother Oncol. 2012 Nov;105(2):161-6. doi: 10.1016/j.radonc.2012.09.006. Epub 2012 Oct 12.

Abstract

Purpose: 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.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / radiotherapy*
  • Dose Fractionation, Radiation
  • Female
  • Glutamates / adverse effects
  • Glutamates / therapeutic use*
  • Guanine / adverse effects
  • Guanine / analogs & derivatives*
  • Guanine / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / radiotherapy*
  • Pemetrexed
  • Prospective Studies
  • Radiotherapy Dosage

Substances

  • Antineoplastic Agents
  • Glutamates
  • Pemetrexed
  • Guanine