Randomized phase II trial of two different schedules of docetaxel plus cisplatin as first‐line therapy in advanced nonsmall cell lung cancer

Abstract

Livers exposed to warm ischemia (WI) before transplantation are at risk for primary nonfunction (PNF), graft dysfunction, and ischemic biliary strictures, all associated with ischemia/reperfusion injury (IRI). Our multifactorial approach, Leuven drug protocol (LDP), has been shown to reduce these effects and increase recipient survival in WI/IRI‐damaged porcine liver transplantation. The aim was the identification of the molecular mechanisms responsible for the hepatoprotective effects of the LDP. Porcine livers were exposed to 45 minutes of WI, cold‐stored for 4 hours, transplanted, and either modulated (LDP group; n = 3) or not modulated (control group; n = 4). In the LDP group, the donor livers were flushed with streptokinase and epoprostenol before cold perfusion; the recipients received intravenous glycine, a‐1‐acid‐glycoprotein, FR167653 (a mitogen‐activated protein kinase inhibitor), a‐tocopherol, glutathione, and apotransferrin. Liver samples were taken before WI and 1 hour after reperfusion. Gene expression was determined with microarrays and molecular pathways and key regulatory genes were identified. The number of genes changed between baseline and 1 hour after reperfusion was 686 in the LDP group and 325 in the control group. The extra genes in the LDP group belonged predominantly to pathways related to cytokine activity, apoptosis, and cell proliferation. We identified 7 genes that were suppressed in the LDP group. These genes could be linked in part to the administered drugs. New potential drug targets were identified on the basis of genes induced in the control group but unaffected in the LDP group and interactions predicted by the literature. In conclusion, the LDP primarily resulted in the suppression of inflammation‐regulating genes in IRI. Furthermore, the microarray technique helped us to identify additional gene targets. Liver Transpl 18:206–218, 2012. © 2011 AASLD.

Phase II trial of weekly docetaxel and gemcitabine for previously untreated, advanced non-small cell lung cancer

“…Gastrointestinal toxicities and fatigue were the predominant adverse events. This finding corresponds with published data on protocols based on weekly docetaxel [15,26].…”

“…The most frequently observed toxicity in these studies was fatigue. We recently compared weekly and 3-weekly schedules of docetaxel/cisplatin in patients with previously untreated NSCLC [26]. Weekly regimen, however, appeared to have no clear advantage over the standard 3-weekly regimen.…”

Phase II Trial of Biweekly Chemotherapy with Docetaxel and Cisplatin in High-Risk Patients with Unresectable Non-Small Cell Lung Cancer

“…However, the weekly schedule showed significantly less myelosuppression and febrile neutropenia [27]. …”

Phase II study of carboplatin, docetaxel and bevacizumab for chemotherapy-naïve patients with advanced non-squamous non-small cell lung cancer

“…The secondary endpoints were the overall response rate (ORR), as assessed by independent reviewers according to the RECIST version 1.1, OS, and safety. As we hypothesized that the addition of bevacizumab might overcome the potential shortcoming of substituting cisplatin with carboplatin, the PFS in three previously published studies [2,24,25] examining docetaxel and cisplatin were consulted. As the reported PFS were 3.7 months [2], 4.3 months [25], and 5.0 months [24], respectively, we estimated the PFS of the regimen as being 4.6 months.…”

“…As we hypothesized that the addition of bevacizumab might overcome the potential shortcoming of substituting cisplatin with carboplatin, the PFS in three previously published studies [2,24,25] examining docetaxel and cisplatin were consulted. As the reported PFS were 3.7 months [2], 4.3 months [25], and 5.0 months [24], respectively, we estimated the PFS of the regimen as being 4.6 months. On the other hand, the PFS of a phase II study with paclitaxel, carboplatin, and bevacizumab that was conducted in Japan was 6.9 months [26].…”