Paclitaxel–Carboplatin Alone or with Bevacizumab for Non–Small-Cell Lung Cancer

Sandler, Alan; Gray, Robert J.; Perry, Michael C.; Brahmer, Julie R.; Schiller, Joan H.; Dowlati, Afshin; Lilenbaum, Rogério; Johnson, David H.

doi:10.1056/nejmoa061884

Cited by 5,366 publications

(3,930 citation statements)

References 18 publications

Supporting

Mentioning

3,740

Contrasting

Unclassified

Order By: Relevance

“…Bevacizumab is the first VEGF inhibitor approved by the FDA for systemic use in cancer. The anti-VEGF antibody is currently approved in combination with intravenous 5-fluorouracil (5-FU)-based chemotherapy, which typically is a combination of irinotecan, 5-FU, and leucovorin (IFL), for first-or second-line treatment of metastatic carcinoma of the colon or rectum (Hurwitz et al, 2004;Hurwitz and Saini, 2006) and, in conjunction with paclitaxel and carboplatin, for first-line treatment of unresectable, locally advanced, recurrent or metastatic nonsquamous, non-small cell lung cancer (NSCLC) (Sandler et al, 2006). Bevacizumab also has activity in breast cancer and kidney cancer.…”

Section: Bevacizumabmentioning

confidence: 99%

Mechanisms of adverse effects of anti-VEGF therapy for cancer

2007

View full text Add to dashboard Cite

Advances in understanding the role of vascular endothelial growth factor (VEGF) in normal physiology are giving insight into the basis of adverse effects attributed to the use of VEGF inhibitors in clinical oncology. These effects are typically downstream consequences of suppression of cellular signalling pathways important in the regulation and maintenance of the microvasculature. Downregulation of these pathways in normal organs can lead to vascular disturbances and even regression of blood vessels, which could be intensified by concurrent pathological conditions. These changes are generally manageable and pose less risk than the tumours being treated, but they highlight the properties shared by tumour vessels and the vasculature of normal organs.

show abstract

Section: Bevacizumabmentioning

confidence: 99%

Mechanisms of adverse effects of anti-VEGF therapy for cancer

2007

View full text Add to dashboard Cite

show abstract

“…Several agents that target vascular endothelial growth factor receptor (VEGFR) have been approved for the treatment of NSCLC. In a first‐line setting, the addition of bevacizumab to chemotherapy significantly improved the clinical outcome with overall survival (OS) of 12.3 months in a Western population and 24.3 months in a Chinese population 8, 9. However, increased toxicity was observed during bevacizumab treatment and class‐related adverse events including hypertension, proteinuria, febrile neutropenia and life‐threatening pulmonary hemorrhage, particularly in squamous NSCLC 8, 9, 10.…”

Section: Introductionmentioning

confidence: 99%

“…In a first‐line setting, the addition of bevacizumab to chemotherapy significantly improved the clinical outcome with overall survival (OS) of 12.3 months in a Western population and 24.3 months in a Chinese population 8, 9. However, increased toxicity was observed during bevacizumab treatment and class‐related adverse events including hypertension, proteinuria, febrile neutropenia and life‐threatening pulmonary hemorrhage, particularly in squamous NSCLC 8, 9, 10. The approval of ramucirumab and nintedanib has provided new options for NSCLC patients who progressed on initial treatment, with improved OS and tolerable toxicity when combined with standard second‐line chemotherapy 11, 12, 13.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of rh‐endostatin (Endostar) combined with pemetrexed/cisplatin followed by rh‐endostatin plus pemetrexed maintenance in non‐small cell lung cancer: A retrospective comparison with standard chemotherapy

Zhou

Zuo²,

et al. 2018

Thoracic Cancer

View full text Add to dashboard Cite

BackgroundRecombinant human endostatin (rh‐endostatin) plus standard chemotherapy in advanced non‐small cell lung cancer (NSCLC) patients has shown improved efficacy; however, it is unclear whether it is effective and safe when added to pemetrexed/cisplatin and used as maintenance therapy.MethodsWe retrospectively evaluated the data of untreated NSCLC patients administered rh‐endostatin plus pemetrexed/cisplatin or pemetrexed/cisplatin. The primary endpoint was progression‐free survival (PFS).ResultsFifty‐six and 39 patients received rh‐endostatin plus pemetrexed/cisplatin and pemetrexed/cisplatin, and 34 and 29 underwent maintenance treatment, respectively. The median PFS was 10 months (95% confidence interval [CI] 5.85–14.15) in the rh‐endostatin and 8.2 months (4.04–12.36) in the chemotherapy group, but the difference was not statistically significant (P = 0.13). In patients administered maintenance treatment, rh‐endostatin plus pemetrexed was associated with prolonged PFS compared to single‐agent pemetrexed when PFS was calculated from first dosing (13.7 [9.41–17.99] vs. 8.2 [4.16–12.24]; P = 0.032); however, PFS did not differ between the groups (hazard ratio 0.618; 95% CI 0.368–1.038; P = 0.069) after adjusting for clinical factors. No difference was observed in the objective response rate between the groups (48.2% vs. 38.5%; P = 0.346), with the exception of men (62.1% vs. 33.3%; P = 0.032) or in the incidence of drug‐related or grade 3–4 adverse events.ConclusionIn previously untreated, advanced‐stage NSCLC patients, first‐line treatment with pemetrexed/cisplatin plus rh‐endostatin did not prolong PFS or overall survival when compared to pemetrexed/cisplatin, but a trend of improved PFS was observed in patients administered maintenance rh‐endostatin plus pemetrexed.

show abstract

“…Angiogenesis inhibitors can be divided into two groups, monoclonal antibodies (Moabs) and small molecule tyrosine kinase inhibitors (TKIs). Bevacizumab is a humanised Moab targeting VEGF, which has shown clinical activity in combination with cytotoxic chemotherapy in metastatic colorectal cancer, non-small cell lung cancer (NSCLC) and breast cancer (Hurwitz et al, 2004;Ramaswamy et al, 2006;Sandler et al, 2006). As single agent bevacizumab has demonstrated acivity in metastatic renal cell carcinoma (Yang et al, 2003).…”

mentioning

confidence: 99%

Vascular disrupting agents in clinical development

2007

View full text Add to dashboard Cite

Growth of human tumours depends on the supply of oxygen and nutrients via the surrounding vasculature. Therefore tumour vasculature is an attractive target for anticancer therapy. Apart from angiogenesis inhibitors that compromise the formation of new blood vessels, a second class of specific anticancer drugs has been developed. These so-called vascular disrupting agents (VDAs) target the established tumour vasculature and cause an acute and pronounced shutdown of blood vessels resulting in an almost complete stop of blood flow, ultimately leading to selective tumour necrosis. As a number of VDAs are now being tested in clinical studies, we will discuss their mechanism of action and the results obtained in preclinical studies. Also data from clinical studies will be reviewed and some considerations with regard to the future development are given.

show abstract

Paclitaxel–Carboplatin Alone or with Bevacizumab for Non–Small-Cell Lung Cancer

Abstract: The addition of bevacizumab to paclitaxel plus carboplatin in the treatment of selected patients with non-small-cell lung cancer has a significant survival benefit with the risk of increased treatment-related deaths. (ClinicalTrials.gov number, NCT00021060.)

Cited by 5,366 publications

References 18 publications

Mechanisms of adverse effects of anti-VEGF therapy for cancer

Mechanisms of adverse effects of anti-VEGF therapy for cancer

Efficacy and safety of rh‐endostatin (Endostar) combined with pemetrexed/cisplatin followed by rh‐endostatin plus pemetrexed maintenance in non‐small cell lung cancer: A retrospective comparison with standard chemotherapy

Vascular disrupting agents in clinical development

Contact Info

Product

Resources

About