Mary M Huerter1, Jane L Meza2, M Sitki Copur3, Addison Tolentino4, Alissa S Marr1, Marsha Ketcham5, Holly DeSpiegelaere6, Susan Kruse5, Mary E Kos5, Karin Swenson7, Sarah E Radniecki5, Anne Kessinger1, Apar Kishor Ganti8. 1. Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, United States. 2. Department of Biostatistics, University of Nebraska Medical Center, Omaha, NE, United States. 3. CHI-St Francis Cancer Treatment Center, Grand Island, NE, United States. 4. Saint Luke's Cancer Institute, Kansas City, MO, United States; Avera Research Institute, Sioux Falls, SD, United States. 5. Early Phase Therapeutic Clinical Trial Unit, Fred and Pamela Buffett Cancer Center, Omaha, NE, United States. 6. Department of Medicine, VA Nebraska Western Iowa Health Care System, Omaha, NE, United States. 7. Avera Research Institute, Sioux Falls, SD, United States. 8. Department of Medicine, VA Nebraska Western Iowa Health Care System, Omaha, NE, United States; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, United States; Early Phase Therapeutic Clinical Trial Unit, Fred and Pamela Buffett Cancer Center, Omaha, NE, United States. Electronic address: aganti@unmc.edu.
Abstract
OBJECTIVE: Platinum-based doublet chemotherapy is the standard for most patients with advanced non-small cell lung cancer (NSCLC). Toxicity concerns limit chemotherapy for patients over 70years. Vinorelbine and paclitaxel are effective as single agents in advanced NSCLC. This phase II study evaluates safety and efficacy of a combination of these two agents in patients >70years with advanced NSCLC. MATERIALS AND METHODS: Patients with treatment naïve metastatic NSCLC received two cycles comprising 6 weekly doses of vinorelbine and paclitaxel, with restaging scans at week 8. Patients with radiographic progression came off study. The estimated sample size was 29. Toxicity analyses were conducted after 10 patients and again after 19 patients were enrolled. Outcomes were safety and efficacy, progression free (PFS) and overall survival (OS) and quality of life (QOL). RESULTS: The study closed at second interim analysis as 6/19 patients had ≥grade 4 non-hematologic toxicity (respiratory failure, sepsis, ischemic encephalopathy, pneumonia, hypoxemia, cardiopulmonary arrest, neutropenic fever, death). Of the 16 evaluable patients, 7 completed the study. Disease control rate (partial response+stable disease) was 47% (n=9); 37% (n=7) progressed. No complete responses were seen. Median PFS was 3.5months (95% CI: 1.4, 5.5) and OS 7.8months (95% CI: 1.9, 13.6). QOL did not change compared to baseline, at week 9, but increased at week 17. CONCLUSIONS: Although the combination met its response end points, increased toxicity makes this combination unsuitable for older patients. While QOL improved over the study, the small sample hinders interpretation. Published by Elsevier Ltd.
OBJECTIVE:Platinum-based doublet chemotherapy is the standard for most patients with advanced non-small cell lung cancer (NSCLC). Toxicity concerns limit chemotherapy for patients over 70years. Vinorelbine and paclitaxel are effective as single agents in advanced NSCLC. This phase II study evaluates safety and efficacy of a combination of these two agents in patients >70years with advanced NSCLC. MATERIALS AND METHODS:Patients with treatment naïve metastatic NSCLC received two cycles comprising 6 weekly doses of vinorelbine and paclitaxel, with restaging scans at week 8. Patients with radiographic progression came off study. The estimated sample size was 29. Toxicity analyses were conducted after 10 patients and again after 19 patients were enrolled. Outcomes were safety and efficacy, progression free (PFS) and overall survival (OS) and quality of life (QOL). RESULTS: The study closed at second interim analysis as 6/19 patients had ≥grade 4 non-hematologic toxicity (respiratory failure, sepsis, ischemicencephalopathy, pneumonia, hypoxemia, cardiopulmonary arrest, neutropenic fever, death). Of the 16 evaluable patients, 7 completed the study. Disease control rate (partial response+stable disease) was 47% (n=9); 37% (n=7) progressed. No complete responses were seen. Median PFS was 3.5months (95% CI: 1.4, 5.5) and OS 7.8months (95% CI: 1.9, 13.6). QOL did not change compared to baseline, at week 9, but increased at week 17. CONCLUSIONS: Although the combination met its response end points, increased toxicity makes this combination unsuitable for older patients. While QOL improved over the study, the small sample hinders interpretation. Published by Elsevier Ltd.