Skip to main content
. 2015 Oct 20;2015(10):CD010463. doi: 10.1002/14651858.CD010463.pub2

Berghmans 2013.

Methods Randomized multi‐center phase III trial
Eligible patients
  • Histological or cytological diagnosis of non‐small cell lung cancer

  • Advanced (unresectable or functionally inoperable) stage III or stage IV disease

  • Availability to participate in detailed follow‐up of the protocol

  • Evaluable or measurable lesion

  • Informed consent


Exclusion criteria
  • Prior treatment with chemotherapy

  • Operable resectable tumor

  • Performance status < 60 on Karnofsky Scale

  • History of prior malignant tumor, except non‐melanoma skin cancer or in situ carcinoma of the cervix, and cured malignant tumor (> 5‐year disease‐free interval)

  • Polynuclear cells < 2000/mm3

  • Platelet cells < 100,000/mm3

  • Serum bilirubin > 1.5 mg/100 mL

  • Serum creatinine > 1.5 mg/100 mL and/or creatinine clearance < 60 mL/min

  • Perception hypoacousia

  • Peripheral neuropathy

  • Recent myocardial infarction (< 3 months before date of diagnosis)

  • Congestive cardiac failure requiring medical therapy or uncontrolled cardiac arrhythmia

  • Uncontrolled infectious disease

  • Serious medical or psychological factors that may prevent adherence to treatment schedule

Participants GIP arm: 231 (ITT population) ‐ median age (range): 58 (29 to 78) years/number of elderly participants not reported
DP arm: 233 (ITT population) ‐ median age (range): 58 (28 to 81) years/number of elderly participants not reported
IG arm: 229 (ITT population) ‐ median age (range): 59 (30 to 84) years/number of elderly participants not reported
Interventions GIP arm: gemcitabine 1000 mg/m2 on days 1 and 8 + ifosfamide 3000 mg/m2 on day 1 + cisplatin 50 mg/m2 on day 1
DP arm: docetaxel 75 mg/m2 + cisplatin 50 mg/m2 on day 1
IG arm: ifosfamide 3000 mg/m2 + gemcitabine 1000 mg/m2 on days 1 and 8
Outcomes Primary endpoint
  • To determine whether cisplatin‐based chemotherapy, cisplatin‐gemcitabine‐ifosfamide, or cisplatin‐docetaxel will better improve survival in comparison with the combination gemcitabine‐ifosfamide in patients with advanced NSCLC


Secondary endpoints
  • To determine the impact of each regimen on best objective response rates

  • To compare toxicity of the 3 regimens

  • To determine activity of salvage regimens: docetaxel after cisplatin‐gemcitabine‐ifosfamide and after gemcitabine‐ifosfamide, and gemcitabine‐ifosfamide after cisplatin‐docetaxel

  • To determine effectiveness of erythropoietin for control of anemia due to cisplatin

Notes No information on number of elderly participants included nor on specific subgroup analysis performed, despite multiple attempts to contact study authors
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk "Central randomisation using a minimization algorithm was performed by calling the ELCWP central office"
Allocation concealment (selection bias) Unclear risk No information on allocation concealment analysis
Blinding of outcome assessment (detection bias) 
 OS and 1y OS rate outcome Unclear risk Study not blinded
Blinding of outcome assessment (detection bias) 
 Other outcomes High risk Study not blinded. "Each patient record will be evaluated for evaluation and response in regular meetings of the Group. Patient's original record and radiological documents have to be available at this time"
Incomplete outcome data (attrition bias) 
 All outcomes Unclear risk "707 patients were randomised, out of whom 14 were ineligible"
Selective reporting (reporting bias) Low risk No evidence of reporting bias
Other bias Unclear risk No separate elderly subgroup analysis