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Abstract: Introduction: This randomised double-blind placebo-controlled study evaluated the addition of cediranib, an inhibitor of vascular endothelial growth factor receptors 1–3, to standard carboplatin/paclitaxel chemotherapy in advanced non-small cell lung cancer. Methods: Eligible patients received paclitaxel (200mg/m2) and carboplatin (area under the concentration time curve 6) intravenously every 3weeks. Daily oral cediranib/placebo 20mg was commenced day 1 of cycle 1 and continued as monotherapy after completion of 4–6 cycles of chemotherapy. The primary end-point of the study was overall survival (OS). The trial would continue to full accrual if an interim analysis (IA) for progression-free survival (PFS), performed after 170 events of progression or death in the first 260 randomised patients, revealed a hazard ratio (HR) for PFS of ⩽0.70. Results: The trial was halted for futility at the IA (HR for PFS 0.89, 95% confidence interval [CI] 0.66–1.20, p =0.45). A final analysis was performed on all 306 enrolled patients. The addition of cediranib increased response rate ([RR] 52% versus 34%, p =0.001) but did not significantly improve PFS (HR 0.91, 95% CI 0.71–1.18, p =0.49) or OS (HR 0.94, 95% CI 0.69–1.30, p =0.72). Cediranib patients had more grade 3 hypertension, diarrhoea and anorexia. Conclusions: The addition of cediranib 20mg daily to carboplatin/paclitaxel chemotherapy increased RR and toxicity, but not survival. [Copyright &y& Elsevier]

Summary: Background: Cisplatin-induced anemia may correlate with adverse events, poor quality of life (QoL), decreased adjuvant chemotherapy (ACT) dose intensity, shorter relapse-free survival (RFS) or overall survival (OS). Methods: The JBR.10 trial demonstrated significantly longer survival with adjuvant cisplatin and vinorelbine (n =242) compared to observation (n =240) in patients with resected NSCLC [Winton T, Livingston R, Johnson D, Rigas J, Johnston M, Butts C, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med 2005;352(25):2640–2]. This exploratory analysis evaluates the predictive value of baseline (in all patients) and during-treatment (in ACT arm only) hemoglobin (Hb) levels on OS and RFS when adjusted for prognostic factors. Baseline (in all patients) and during treatment (in ACT arm only) Hb levels were also correlated with adverse events, QoL, morbidity and ACT dose intensity. Results: Baseline Hb did not predict RFS or OS. However, there was a trend to shorter OS (p =0.1) when baseline Hb was <120g/L. Lower baseline Hb predicted increased hospitalization (p =0.04) and worse QoL (SOB item, p =0.03) but had no impact on adverse events or dose intensity. There was a trend to longer RFS (p =0.08) in patients with lower nadir during-treatment Hb and to longer OS (p =0.06) and RFS (p =0.08) in patients with maximum during-treatment Hb drop >30% that was not maintained when ACT dose intensity was included in the model. Maximum during-treatment Hb drop >30% correlated with increased lethargy (p =0.003) and worse QoL (fatigue item, p =0.07). Conclusions: Lower baseline and during-treatment Hb levels seem associated with poorer QoL, fatigue and increased hospitalization. There is a trend for shorter OS in patients with lower baseline Hb levels. [Copyright &y& Elsevier]