The purpose of this study is to evaluate the tolerability and efficacy of the addition of rofecoxib to first-line chemotherapy, and to evaluate the efficacy of prolonged continuous infusion of gemcitabine in combination with cisplatin in the treatment of patients affected by advanced non-small cell lung cancer.

The primary end-points of the GECO study

• To evaluate the tolerability of three innovative schedules of treatment for advanced NSCLC
• To evaluate the efficacy of the addition of rofecoxib to first-line chemotherapy in the treatment of patients affected by advanced NSCLC
• To evaluate the efficacy of prolonged continuous infusion (p.c.i.) of gemcitabine, with the fixed infusion rate of 10 mg/sqm/minute) versus the standard administration in 30 minutes, in combination with cisplatin, in the treatment of patients affected by advanced NSCLC

Four treatment arms are planned.

• ARM A standard treatment : cisplatin + gemcitabine
• ARM B cisplatin + gemcitabine + rofecoxib
• ARM C cisplatin + p.c.i. gemcitabine (10 mg/sqm/minute)
• ARM D cisplatin + p.c.i gemcitabine (10 mg/sqm/minute) + rofecoxib

The phase II part of the study for experimental arms B, C and D will be conducted to evaluate tolerability in the three treatment arms.

The phase III study for efficacy has been designed according to a factorial 2x2 model with the planned comparison of

• The efficacy of rofecoxib: A + C (arms without rofecoxib) vs B+D (arms with rofecoxib)
• The efficacy of p.c.i. gemcitabine: A + B (arms with standard infusion of gemcitabine) vs C+ D (arms with p.c.i gemcitabine)

Inclusion Criteria:

• Cytologic or histologic diagnosis of non-small cell lung cancer
• Disease stage IIIB or IV
• Age less than 70 years
• ECOG performance status 2 or less
• Patients with cerebral metastases are permitted if they are asymptomatic and do not require radiation therapy concomitant with chemotherapy
• Negative history of allergy to non-steroidal anti-inflammatory and/or sulphonamide drugs
• Patients previously treated with radiation therapy are permitted if at least 4 weeks have passed since last therapy
• Written informed consent

Exclusion Criteria:

• Previous chemotherapy
• Previous or concomitant malignant neoplasm (excluding adequately treated baso or spinocellular skin carcinoma or carcinoma in situ of the cervix)
• Neutrophil < 2000/mm3, platelets < 100,000/mm3, haemoglobin < 10 g/dl
• Creatinine > 1.25 x the upper normal limits
• GOT and/or GPT and/or Bilirubin > 1.25 the upper normal limits in absence of hepatic metastases
• GOT and/or GPT and/or Bilirubin > 2.5 the upper normal limits in presence of hepatic metastases
• Any concomitant pathology that would, in the investigator's opinion, contraindicate the use of the drugs in this study
• Inability to comply with follow-up