Taxanes as first-line therapy for advanced non-small cell lung cancer: A systematic review and practice guideline

Lee

International Journal of Oncology

et al. 2013

Abstract. Osteosarcoma (OS) is the most common primary malignant bone cancer in children and adolescents. Although paclitaxel (PCX) has been considered one of the most important cancer chemotherapeutic drugs, the current protocols for OS treatment do not incorporate this agent. Therefore, the purpose of this study was to evaluate the induction of cell death in OS cells after exposure to PCX, to identify the cell death mechanism(s) activated by PCX and to investigate whether autophagy is associated with PCX-induced apoptosis. The results of the present study confirmed that exposure to low PCX concentrations can induce apoptotic cell death in Saos-2 cells; furthermore, caspase-3 activation, PARP degradation and XIAP downregulation were observed in combination with PCX-induced apoptosis. The potential involvement of mitochondrial events (intrinsic apoptotic pathway) in PCX-induced apoptosis in OS cells was verified by the alteration (depolarization) of mitochondrial membrane potential. In addition, pretreatment with 3-methyladenine (3-MA), a specific inhibitor of autophagy, significantly increased PCX-induced apoptotic cell death in Saos-2 cells. The augmentation of PCX-induced apoptosis by 3-MA was accompanied by increase in the cytochrome c release from the mitochondria, caspase-3 activity and XIAP downregulation, which suggests that inhibiting autophagy further stimulates the PCX-induced mitochondrionrelated (intrinsic) apoptotic pathway by provoking caspase-3 activation. Thus, autophagy observed during PCX-induced apoptosis in Saos-2 OS cells represents the role of cytoprotection in cellular homeostatic processes. In conclusion, the results of this study revealed that PCX exposure effectively induces OS cell death by apoptosis associated with the mitochondrial-mediated caspase-dependent pathway. PCX can increase autophagic activity and suppressing autophagy enhances PCX-induced apoptosis in OS cells. Therefore, it is suggested that combination treatment involving low-dose PCX therapy and autophagy inhibitor therapy could be an effective and potent strategy for improved chemotherapy for OS in the near future.

Section: Discussionmentioning

confidence: 99%

Cytoprotective role of autophagy during paclitaxel-induced apoptosis in Saos-2 osteosarcoma cells

Lee

International Journal of Oncology

et al. 2013

Clinical Cancer Research

“…We showed that a combinational use of nitroglycerin plus vinorelbine and cisplatin regimen improves the response rate to 72% and median time to progression (TTP) to 11 months in comparison with vinorelbine and cisplatin alone in previously untreated stage IIIB/IV patients with NSCLC in a phase II trial, showing the additional effect of nitroglycerin on vinorelbine and cisplatin regimen (30). Taxanes, including docetaxel and paclitaxel, are widely used for chemotherapy in patients with advanced NSCLC (29). However, the effects and their mechanisms of nitroglycerin on the increase in response to docetaxel and carboplatin regimen (DCb) in patients with lung adenocarcinoma, in vivo, have not been reported.…”

mentioning

confidence: 99%

Nitroglycerin Treatment May Enhance Chemosensitivity to Docetaxel and Carboplatin in Patients with Lung Adenocarcinoma

Yasuda

Nakayama

Watanabe³

et al. 2006

112

Purpose: Nitroglycerin may improve the response to chemotherapy in advanced non^small cell lung cancer. The effects and mechanisms of nitroglycerin on the enhancement of chemosensitivity to docetaxel and carboplatin regimen (DCb) in patients with lung adenocarcinoma have not been reported. Experimental Design: Seventeen patients with operable lung adenocarcinoma and stable angina pectoris were selected to investigate the effects of nitroglycerin on immunoreactivity for hypoxia-inducible factor 1a (HIF-1a), vascular endothelial growth factor (VEGF), P-glycoprotein (P-gp), the production of which is regulated by HIF-1, and p53 proteins in their resected tumor by semiquantitative immunohistochemical analyses. Eight of 17 patients were treated with nitroglycerin patches before operation, but 9 of 17 patients were not. Furthermore, to study the relationship between changes in plasmaVEGF levels by nitroglycerin treatment and response to DCb, 29 patients with advanced lung adenocarcinoma were treated with nitroglycerin for 3 days before chemotherapy using DCb. Results: The rates of immunoreactive cells for HIF-1a, VEGF, and P-gp in tumor tissues treated with nitroglycerin were lower than those without nitroglycerin, but those for p53 were not different between those treated with and without nitroglycerin. Furthermore, the rates of immunoreactive cells for VEGF and P-gp proteins were significantly associated with those for HIF-1ain tumor tissue. The magnitude of decrease in plasma VEGF levels after treatment with nitroglycerin was significantly associated with response to DCb in patients with advanced lung adenocarcinoma. Conclusions: Nitroglycerin treatment may improve response to DCb in patients with lung adenocarcinoma, partly through decreasingVEGF and P-gp production via reduction of HIF-1a.

“…The combination of cisplatin with docetaxel does not appear to result in better survival in comparison to other cisplatin-based regimens [39] but seems superior to regimens based on platinum and vinca alkaloids [40]. In 2005, Canadian practice guidelines about the use of taxanes recommended paclitaxel or docetaxel plus cisplatin as one of a number of chemotherapy options in patients with good performance status [41]. Finally, a study group tried to compare regimens with second-generation or third-generation platinum-based regimens but decided to not perform survival aggregation because of too high a heterogeneity [42].…”

Section: Lung Cancer Chemotherapy J-p Sculier and D Moro-sibilotmentioning

confidence: 99%

First- and second-line therapy for advanced nonsmall cell lung cancer

Sculier¹,

Moro-Sibilot²

2009

Eur Respir J

The objectives for the treatment of advanced nonsmall cell lung cancer are palliative and include improvement of survival, symptom control, quality of life and cost. The level of evidence of these benefits is based on multiple randomised trials and meta-analyses. Cisplatinbased chemotherapy with one of the regimens shown to be effective should be preferred. Carboplatin may be substituted for cisplatin if medical contraindications exist. Nonplatinumbased regimens are indicated as first-line treatment for advanced nonsmall cell lung cancer in patients for whom platinum-based chemotherapy is contraindicated. Single drug chemotherapy may be considered in patients with poor performance status. The choice of the active drugs depends on the patient's medical condition. There is no conclusive evidence that high doses of cisplatin (100-120 mg?m -2 ) provide better results than standard lower doses (50-60 mg?m -2 ) in terms of survival. The optimal duration of chemotherapy is poorly documented in advanced nonsmall cell lung cancer. A minimum of four to six cycles is advised in responding patients. Second-line chemotherapy is now accepted as a standard and should be offered to patients with good performance status and failing platinum-based first-line chemotherapy. Evidence is in favour of docetaxel and in the case of adenocarcinoma and adequate renal function, pemetrexed is recommended.