MILES-02: Study of Chemotherapy Treatment and Toxicity in Elderly Patients With Advanced Non Small Cell Lung Cancer

Phase II Study of Chemotherapy With Gemcitabine in Prolonged Infusion or With Schedules With Cisplatin in Non-small Cell Lung Cancer Elderly Patients

The main purpose of this study is to describe activity and toxicity of single-agent gemcitabine given as prolonged infusion, and of two 2-drug combinations containing cisplatin (cisplatin + vinorelbine, and cisplatin + gemcitabine) in the treatment of elderly patients with advanced non small cell lung cancer

The study design includes three parallel phase II studies, all with the same rules for patient selection and outcome assessment. In the two studies of cisplatin-based doublets, a dose-finding phase is planned, with subsequent cohorts of 6 patients treated with increasing doses of cisplatin (50-60-70 mg/m²). Following this phase, patients will be assigned to the three studies through a randomization procedure, to reduce selection biases.

Arm A: gemcitabine:

Gemcitabine 1200 mg/m2 intravenously in 2 hours (10 mg/m²/minute) on days 1 & 8 of each cycle, every 21 days, for a maximum of 6 cycles.

Arm B: cisplatin + vinorelbine:

Vinorelbine 25 mg/m² on days 1 & 8, followed by Cisplatin (50 or 60 or 70 mg/m²) on day 1 of each cycle, every 21 days, for a maximum of 6 cycles.

Arm C: cisplatin + gemcitabine:

Gemcitabine 1000 mg/m2,, on days 1 & 8, followed by Cisplatin (50 or 60 or 70 mg/m²) on day 1 of each cycle, every 21 days, for a maximum of 6 cycles.

Inclusion Criteria:

• Histologic or cytologic diagnosis of NSCLC
• Stage IV or IIIB with pleural effusion or metastatic supraclavicular lymphoadenopathy
• Age > o = 70 years.
• Written informed consent.

Exclusion Criteria:

• Performance status (ECOG) ³2
• Previous chemotherapy.
• Symptomatic brain metastases requiring synchronous radiotherapy
• Previous radiotherapy (completed less than 4 weeks before enrollment)
• Previous or synchronous malignant disease (except adequately treated non melanomatous skin cancer or carcinoma in situ of the cervix) if diagnosed in the last five years before enrollment.
• Neutrophils < 2.000/mm³ or platelets < 100.000/mm³ or hemoglobin < 10 g/dl.
• Serum creatinine > 1.5 times the UNL.
• GOT and/or GPT >1.25 times the UNL or serum total bilirubin >1.25 times the UNL without hepatic metastases.
• GOT and/or GPT >2.5 times the UNL or serum total bilirubin >1.5 times the UNL with hepatic metastases.
• Other concomitant diseases contraindicating the study treatments.
• Refusal of written informed consent.
• Follow-up impossible.