A Phase II study of pulse dose imatinib mesylate and weekly paclitaxel in patients aged 70 and over with advanced non-small cell lung cancer

BACKGROUND: In non-small cell lung cancer (NSCLC), interstitial hypertension is a barrier to chemotherapy delivery, and is mediated by platelet derived growth factor receptor (PDGFR). Antagonizing PDGFR with imatinib may improve intra-tumoral delivery of paclitaxel, increasing response rate (RR). METHODS: This single-stage, open-label phase II study evaluated pulse dose imatinib and weekly paclitaxel in elderly patients with advanced NSCLC. Eligible patients were aged ≥ 70 with untreated, stage IIIB-IV NSCLC and ECOG performance status 0-2. Primary endpoint was RR. Secondary endpoints included median progression free and overall survival (PFS, OS) and correlatives of PDGFR pathway activation. Baseline Charlson Comorbidity Index (CCI) and Vulnerable Elder Survey-13 (VES-13) were correlated with outcomes. RESULTS: Thirty-four patients with median age 75 enrolled. Eleven of 29 (38%) were frail by VES-13 score. Overall RR was 11/34 (32%; 95% CI 17%-51%), meeting the primary endpoint. Median PFS and OS were 3.6 and 7.3 months, respectively. High tumoral PDGF-B expression predicted inferior PFS. Frail patients by VES-13 had significantly worse median PFS (3.2 vs. 4.5 months; p=0.02) and OS (4.8 vs. 12 months; p=0.02) than non-frail. CONCLUSIONS: The combination of imatinib and paclitaxel had encouraging activity as measured by the primary endpoint of RR. However, PFS and OS were typical for elderly patients treated with single agent chemotherapy and the regimen is not recommended for further study. Adjunct imatinib did not overcome the established association of tumoral PDGF-B expression with inferior PFS. VES-13 was a powerful predictor of poor survival outcomes. Frailty should be further studied as a predictor of non-benefit from chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT01011075

Number preferences in lotteries

We explore people's preferences for numbers in large proprietary data sets from two different lottery games. We find that choice is far from uniform, and exhibits some familiar and some new tendencies and biases. Players favor personally meaningful and situationally available numbers, and are attracted towards numbers in the center of the choice form. Frequent players avoid winning numbers from recent draws, whereas infrequent players chase these. Combinations of numbers are formed with an eye for aesthetics, and players tend to spread their numbers relatively evenly across the possible range

A Phase II study of pulse dose imatinib mesylate and weekly paclitaxel in patients aged 70 and over with advanced non-small cell lung cancer

Abstract Background In non-small cell lung cancer (NSCLC), interstitial hypertension is a barrier to chemotherapy delivery, and is mediated by platelet derived growth factor receptor (PDGFR). Antagonizing PDGFR with imatinib may improve intra-tumoral delivery of paclitaxel, increasing response rate (RR). Methods This single-stage, open-label phase II study evaluated pulse dose imatinib and weekly paclitaxel in elderly patients with advanced NSCLC. Eligible patients were aged ≥ 70 with untreated, stage IIIB-IV NSCLC and ECOG performance status 0-2. Primary endpoint was RR. Secondary endpoints included median progression free and overall survival (PFS, OS) and correlatives of PDGFR pathway activation. Baseline Charlson Comorbidity Index (CCI) and Vulnerable Elder Survey-13 (VES-13) were correlated with outcomes. Results Thirty-four patients with median age 75 enrolled. Eleven of 29 (38%) were frail by VES-13 score. Overall RR was 11/34 (32%; 95% CI 17%-51%), meeting the primary endpoint. Median PFS and OS were 3.6 and 7.3 months, respectively. High tumoral PDGF-B expression predicted inferior PFS. Frail patients by VES-13 had significantly worse median PFS (3.2 vs. 4.5 months; p=0.02) and OS (4.8 vs. 12 months; p=0.02) than non-frail. Conclusions The combination of imatinib and paclitaxel had encouraging activity as measured by the primary endpoint of RR. However, PFS and OS were typical for elderly patients treated with single agent chemotherapy and the regimen is not recommended for further study. Adjunct imatinib did not overcome the established association of tumoral PDGF-B expression with inferior PFS. VES-13 was a powerful predictor of poor survival outcomes. Frailty should be further studied as a predictor of non-benefit from chemotherapy. Trial Registration ClinicalTrials.gov NCT01011075</p