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

• Published in: Journal of thoracic oncology Vol. 7; no. 1; pp. 196 - 202
• Main Authors: Spigel, David R., Hainsworth, John D., Shipley, Dianna L., Ervin, Thomas J., Kohler, Peter C., Lubiner, Eric T., Peyton, James D., Waterhouse, David M., Burris, Howard A., Greco, F. Anthony
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2012; International Association for the Study of Lung Cancer
• Subjects: Aged; Aged, 80 and over; Anemia - chemically induced; Antibodies, Monoclonal, Humanized - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bevacizumab; Carboplatin - administration & dosage; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Disease Progression; Elderly; Fatigue - chemically induced; Female; Glutamates - administration & dosage; Guanine - administration & dosage; Guanine - analogs & derivatives; Humans; Infection - chemically induced; Kaplan-Meier Estimate; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Neutropenia - chemically induced; Non-small cell lung cancer; Pemetrexed; Thrombocytopenia - chemically induced; Thromboembolism - chemically induced; Time Factors; Treatment Outcome; Elderly; Pemetrexed; Non-small cell lung cancer; Bevacizumab
• ISSN: 1556-0864; 1556-1380
• DOI: 10.1097/JTO.0b013e3182307efe

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. 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. 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). 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.