MILES-4: Study Comparing Gemcitabine and Pemetrexed, With or Without Cisplatin, in Patients With Nonsquamous Lung Cancer

A Factorial Study Comparing Pemetrexed With Gemcitabine and Testing the Efficacy of the Addition of Cisplatin in Elderly Patients With Non Squamous Advanced, Metastatic or Recurrent NSCLC.

The purposes of this study are to test whether the addition of cisplatin to single agent chemotherapy (either gemcitabine or pemetrexed) prolongs survival in elderly patients with non squamous non small cell lung cancer (NSCLC), and to test whether pemetrexed prolongs survival as compared to gemcitabine in elderly patients with non squamous NSCLC.

Inclusion Criteria:

• Diagnosis of cytologically or histologically confirmed non-small cell lung cancer.
• Non squamous tumor type (including those with a non-specified tumor type).
• Metastatic (stage IV, both M1A or M1B) or locally advanced (stage IIIB, with metastasis to supraclavicular nodes) according to TNM VII edition.
• Both patients at first diagnosis or those with disease recurrence after former surgery are eligible.
• At least one target or non-target lesion according to RECIST revised version 1.1.
• Male or female > or = 70 years of age.
• ECOG PS 0 or 1.
• Life expectancy > 3 months.
• Neutrophils > or = 1500 mm3, platelets > or = 100000 mm3, and haemoglobin > or = 9 g/dL.
• Bilirubin level either normal or < 1.5 x ULN.
• AST (SGOT) and ALT (SGPT) < or = 2.5 x ULN (< or = 5 x ULN if liver metastasis are present).
• Serum creatinine < 1.5 x ULN.
• Signed written informed consent.

Exclusion Criteria:

• Prior chemotherapy or therapy with systemic anti-neoplastic therapy for advanced disease. Prior surgery and/or localised irradiation is permitted. Prior adjuvant chemotherapy is permitted if it did not contain gemcitabine and pemetrexed and if at least 6 months elapsed from the end of adjuvant chemotherapy.
• Any unstable systemic disease (including active infections, significant cardiovascular disease or myocardial infarction within the previous year, any significant hepatic, renal or metabolic disease), metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of study medications or render the patient at high risk from treatment complications.
• Any other malignancies within 5 years (except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer or surgically resected prostate cancer with normal PSA).
• Patients with symptomatic brain metastasis or spinal cord compression that has not yet been treated with surgery and/or radiation; patients with CNS metastases or spinal cord compression previously treated with surgery and/or radiation are eligible if they are asymptomatic and do not require steroids (anti-seizure medications are allowed).
• Known or suspected hypersensitivity to any of the study drugs