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.

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.

• Authors: Giovanna Mantini, Vincenzo Valentini, Bruno Meduri, Stefano Margaritora, Mario Balducci, Francesco Micciché, Luigia Nardone, Fiorenza De Rose, Alfredo Cesario, Anna Rita Larici, Fabio Maggi, Maria Lucia Calcagni, Pierluigi Granone
• Journal: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology (Radiother Oncol) Vol. 105 Issue 2 Pg. 161-6 (Nov 2012) ISSN: 1879-0887 [Electronic] Ireland
• PMID: 23068709 (Publication Type: Clinical Trial, Phase II, Journal Article)
• Copyright: Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Glutamates
• Pemetrexed
• Guanine

Topics

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