title: A randomized phase II trial of pemetrexed/gemcitabine/bevacizumab or pemetrexed/carboplatin/bevacizumab in the first-line treatment of elderly patients with advanced non-small cell lung cancer.
abstract: OBJECTIVE
  To assess time to progression (TTP) in elderly patients with previously untreated nonsquamous non-small cell lung cancer treated with pemetrexed/gemcitabine/bevacizumab or pemetrexed/carboplatin/bevacizumab.
  
  
  METHODS
  Eligible patients were aged 70 years or older with newly diagnosed stage IIIB/IV nonsquamous non-small cell lung cancer; Eastern Cooperative Oncology Group performance status 0 to 1; adequate organ function; and no active central nervous system metastasis. Patients were randomized 1:1 to cohort A (pemetrexed 500 mg/m2 IV, gemcitabine 1500 mg/m2 IV, and bevacizumab 10 mg/kg IV; days 1 and 15 of 28-day cycles) or cohort B (pemetrexed 500 mg/m2 IV, carboplatin area under the concentration-time curve =5 IV, and bevacizumab 15 mg/kg IV; day 1 of 21-day cycles). After six cycles, stable/responding patients continued bevacizumab until disease progression.
  
  
  RESULTS
  Between March 2007 and December 2009, 110 patients (median age, 76 years; 88% stage IV) were treated for medians of 2.5 cycles (cohort A) and 6 cycles (cohort B). Overall response rate was 35% in both cohorts, with stable disease rates of 33% (A) and 45% (B). TTP by cohort was 4.7 and 10.2 months with median OS 7.5 and 14.8 months, respectively. Severe toxicities included the following: neutropenia (A, 51% and B, 45%), fatigue (A, 36% and B, 18%), anemia (A, 22% and B, 7%), infection (A, 25% and B, 7%), thrombocytopenia (A, 11% and B, 31%), and thromboembolism (A, 7% and B, 7%). Three potential treatment-related deaths occurred in cohort A (sepsis, thrombocytopenia, and myocardial infarction) and two in B (sepsis and pulmonary hemorrhage).
  
  
  CONCLUSIONS
  Treatment with pemetrexed/carboplatin/bevacizumab was associated with improved TTP and OS in this elderly population and should be further evaluated. Treatment-related toxicities were expected and usually manageable, although deaths occurred with both regimens.
authors: Sarah Cannon Research Institute, Nashville, Tennessee 37203, USA. dspigel@tnonc.com
authors: David R
authors: DR
authors: Spigel
authors: John D
authors: JD
authors: Hainsworth
authors: Dianna L
authors: DL
authors: Shipley
authors: Thomas J
authors: TJ
authors: Ervin
authors: Peter C
authors: PC
authors: Kohler
authors: Eric T
authors: ET
authors: Lubiner
authors: James D
authors: JD
authors: Peyton
authors: David M
authors: DM
authors: Waterhouse
authors: Howard A
authors: HA
authors: Burris
authors: F Anthony
authors: FA
authors: Greco
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D007239:Infections / Q000139:chemically induced; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009503:Neutropenia / Q000139:chemically induced; D000068437:Pemetrexed; D013921:Thrombocytopenia / Q000139:chemically induced; D013923:Thromboembolism / Q000139:chemically induced; D013997:Time Factors; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D005971:Glutamates; D000068437:Pemetrexed; D003841:Deoxycytidine; D000068258:Bevacizumab; D006147:Guanine; D016190:Carboplatin; D000093542:Gemcitabine