chemotherapy plus bevacizumab in elderly non-small cell lung cancer patients

Conditions: Non-small Cell Lung Cancer (NSCLC)

Summary: a phase ii study of an adapted chemotherapy regimen plus bevacizumab in elderly non-small cell lung cancer patients selected by geriatric assessment

criterios inclusion * written informed consent confirming that the patient understands the study objective and the procedures required. * patients must be able to accomplish with the study protocol. * men and women ≥70 years old. * histologically or cytologically confirmed diagnosis of non-squamous non-small cell lung cancer (nsclc) with egfr gen mutational status negative or non-determinable. * patients with stage iv disease. * patients who have not received first-line treatment * patients with ecog performance status 0 or 1. * adequate bone marrow function, defined as: * absolute neutrophil count (anc) ≥1.500/mm3 or ≥1.5x109/l; * hemoglobin ≥ 9 g/dl. * platelet count ≥ 100.000/mm3. * adequate renal function, defined as: * creatinine clearance ≥ 40 ml/min, according to mdrd formula. * urine dipstick proteinuria \<2+. if urine dipstick for proteinuria ≥2+ 24 hours urine must be collected within 24 hours, and proteins must be less than 1 g. * fertile males must use an effective contraceptive method (error rate per year \<1%) during the trial and until 6 months after the last study treatment dose, such as sexual abstinence, previous vasectomy and/or having a partner using any of following methods: implantables, injections, combined oral contraceptives and/or intrauterine device (hormonal only). criterios exclusion * previous chemotherapy for advanced nsclc. * history of haemoptysis grade ≥ 2 (defined as at least 2.5 ml of bright red blood) in the 3 months before inclusion. * major surgery (including open biopsy), significant traumatic injuries in the 28 days before inclusion or anticipation of the need of major surgical procedure during the treatment period * minor surgery, including permanent catheter insertion, in the 24 hours before bevacizumab infusion. * untreated brain metastases. patients with cns metastases treated with radiotherapy or surgery may be included if there is no evidence of progression after treatment * radiological evidence of a tumor that invades or is adjacent to a main blood vessel (e.g. lung artery or superior cava venous). * radiotherapy, in any lesion and for any reason, within 28 days before inclusion. palliative radiotherapy for bone lesions within 14 days before inclusion is allowed. * treatment with aspirin (\>325 mg/day) or clopidogrel (\>75 mg/day) within 10 days prior to bevacizumab first dose. use of full dose of oral or parenteral anticoagulants or thrombolytic agents in therapeutic doses. prophylactic use of anticoagulant therapy is allowed. * uncontrolled hypertension (systolic bp \>140 mmhg, diastolic bp \>90mmhg) in the 28 days previous to inclusion or history of hypertensive crisis, or hypertensive encephalopathy. * clinically significant cardiovascular disease (i.e. cerebrovascular accident (cva), myocardial infarction within 6 months prior to inclusion, unstable angina, congestive cardiac insufficiency nyha ≥ ii, left ventricular ejection fraction (lvef) \<50% or serious cardiac arrhytmia), not responding to treatment or that can interfere with trial treatment administration. * not healed wounds, active peptic ulcer or untreated bone fracture. * hypersensibility to any of the active ingredients of the study treatment (bevacizumab, carboplatine and paclitaxel) or any of its excipients. * serious cognitive impairment that limits the patient to understand and answer the study questionnaires. * inability to comply with the study protocol and/or follow-up procedures due to psychological, familiar, social or geographical problems * patients with an adl score \<5 at the screening. * patients with dementia: 9-12 points in the folstein mms at the screening. * patients accomplishing fragility balducci criteria at the screening: * age ≥ 85 years old * dependence in 1 or more adl * \>3 comorbilities * \>1 geriatric syndrome objetivos to assess the toxicity of the treatment in elderly patients (≥70 years) with nsc lung cancer who meet inclusion criteria for bevacizumab and selected based on a geriatric evaluation. determine predictive factors of toxicity in the elderly population (≥70 years). determine objective response rate determine disease control rate determine progression free survival determine overall survival determine safety of the treatment combination variables primary endpoint: rate of grade 3-4 neutropenia defined according to national cancer institute common terminology criteria version 4.0 (nci-ctc v4.0). secondary endpoints: * items of the comprehensive geriatric assessment (cga) scale as predictive factors for toxicity end-points. * objective response according to the response evaluation criteria in solid tumors (recist v1.1). * progression-free survival. * overall survival.

Eligibility criteria:
inclusion criteria: * written informed consent confirming that the patient understands the study objective and the procedures required. * patients must be able to accomplish with the study protocol. * men and women ≥70 years old. * histologically or cytologically confirmed diagnosis of non-squamous non-small cell lung cancer (nsclc) with egfr gen mutational status negative or non-determinable. * patients with stage iv disease. * patients who have not received first-line treatment * patients with ecog performance status 0 or 1. * adequate bone marrow function, defined as: absolute neutrophil count (anc) ≥1.500/mm3 or ≥1.5x109/l; hemoglobin ≥ 9 g/dl. platelet count ≥ 100.000/mm3. • adequate renal function, defined as: creatinine clearance ≥ 40 ml/min, according to mdrd formula. urine dipstick proteinuria \<2+. if urine dipstick for proteinuria ≥2+ 24 hours urine must be collected within 24 hours, and proteins must be less than 1 g. • fertile males must use an effective contraceptive method (error rate per year \<1%) during the trial and until 6 months after the last study treatment dose, such as sexual abstinence, previous vasectomy and/or having a partner using any of following methods: implantables, injections, combined oral contraceptives and/or intrauterine device (hormonal only). exclusion criteria: * previous chemotherapy for advanced nsclc. * history of haemoptysis grade ≥ 2 (defined as at least 2.5 ml of bright red blood) in the 3 months before inclusion. * major surgery (including open biopsy), significant traumatic injuries in the 28 days before inclusion or anticipation of the need of major surgical procedure during the treatment period * minor surgery, including permanent catheter insertion, in the 24 hours before bevacizumab infusion. * untreated brain metastases. patients with cns metastases treated with radiotherapy or surgery may be included if there is no evidence of progression after treatment * radiological evidence of a tumor that invades or is adjacent to a main blood vessel (e.g. lung artery or superior cava venous). * radiotherapy, in any lesion and for any reason, within 28 days before inclusion. palliative radiotherapy for bone lesions within 14 days before inclusion is allowed. * treatment with aspirin (\>325 mg/day) or clopidogrel (\>75 mg/day) within 10 days prior to bevacizumab first dose. use of full dose of oral or parenteral anticoagulants or thrombolytic agents in therapeutic doses. prophylactic use of anticoagulant therapy is allowed. * uncontrolled hypertension (systolic bp \>140 mmhg, diastolic bp \>90mmhg) in the 28 days previous to inclusion or history of hypertensive crisis , or hypertensive encephalopathy. * clinically significant cardiovascular disease (i.e. cerebrovascular accident (cva), myocardial infarction within 6 months prior to inclusion, unstable angina, congestive cardiac insufficiency nyha ≥ ii, left ventricular ejection fraction (lvef) \<50% or serious cardiac arrhythmia), not responding to treatment or that can interfere with trial treatment administration. * not healed wounds, active peptic ulcer or untreated bone fracture. * hypersensibility to any of the active ingredients of the study treatment (bevacizumab, carboplatine and paclitaxel) or any of its excipients. * serious cognitive impairment that limits the patient to understand and answer the study questionnaires. * inability to comply with the study protocol and/or follow-up procedures due to psychological, familiar, social or geographical problems * patients with an adl score \<5 at the screening. * patients with dementia: 9-12 points in the folstein mms at the screening. * patients accomplishing fragility balducci criteria at the screening: age ≥ 85 years old dependence in 1 or more adl \>3 comorbidities \>1 geriatric syndrome