Concurrent chemoradiotherapy in non-small cell lung cancer.
BACKGROUND
This is an updated version of the original review published in Issue 4, 2004. The use of concurrent chemotherapy and radiotherapy in non-small cell lung cancer (NSCLC) might be seen as a way of increasing the effectiveness of radical radiotherapy at the same time as reducing the risks of metastatic disease.


OBJECTIVE
To determine the effectiveness of concurrent chemoradiotherapy as compared to radiotherapy alone with regard to overall survival, tumour control and treatment-related morbidity. To determine the effectiveness of concurrent versus sequential chemoradiotherapy.


METHODS
For this update we ran a new search in October 2009, using a search strategy adapted from the design in the original review. We searched: CENTRAL (accessed through The Cochrane Library, 2009, Issue 4), MEDLINE (accessed through PubMed), and EMBASE (accessed through Ovid).


METHODS
Randomised trials of patients with stage I-III NSCLC undergoing radical radiotherapy and randomised to receive concurrent chemoradiotherapy versus radiotherapy alone, or concurrent versus sequential chemoradiotherapy.


METHODS
Study selection, data extraction and assessment of risk of bias was performed independently by two authors. Pooled hazard ratios and relative risks were calculated according to a random-effects model.


RESULTS
Nineteen randomised studies (2728 participants) of concurrent chemoradiotherapy versus radiotherapy alone were included. Chemoradiotherapy significantly reduced overall risk of death (HR 0.71, 95% CI 0.64 to 0.80; I(2) 0%; 1607 participants) and overall progression-free survival at any site (HR 0.69, 95% CI 0.58 to 0.81; I(2) 45%; 1145 participants). Incidence of acute oesophagitis, neutropenia and anaemia were significantly increased with concurrent chemoradiation. Six trials (1024 patients) of concurrent versus sequential chemoradiation were included. A significant benefit of concurrent treatment was shown in overall survival (HR 0.74, 95% CI 0.62 to 0.89; I(2) 0%; 702 participants). This represented a 10% absolute survival benefit at 2 years. More treatment-related deaths (4% vs 2%) were reported in the concurrent arm without statistical significance (RR 2.02, 95% CI 0.90 to 4.52; I(2) 0%; 950 participants). There was increased severe oesophagitis with concurrent treatment (RR 4.96, 95%CI 2.17 to 11.37; I(2) 66%; 947 participants).


CONCLUSIONS
This update of the review published in 2004 incorporates additional trials and more mature data. It demonstrates the benefit of concurrent chemoradiation over radiotherapy alone or sequential chemoradiotherapy. Patient selection is an important consideration in view of the added toxicity of concurrent treatment. Uncertainty remains as to how far this is purely due to a radiosensitising effect and whether similar benefits could be achieved by using modern radiotherapy techniques and more dose intensive accelerated and/ or hyperfractionated radiotherapy regimens.
O'Rourke
Noelle
N
Beatson Oncology Centre, Gartnavel General Hospital, Glasgow, UK, G12 0YN.
Roqué I Figuls
Marta
M
Farré Bernadó
Nuria
N
Macbeth
Fergus
F
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods / Q000401:mortality; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic
D011838:Radiation-Sensitizing Agents