A phase I trial of erlotinib and bexarotene as a targeted combination therapy for aerodigestive tract cancers

Dragnev, Konstantin H.; Petty, W. Jeffrey; Shah, Sameena; Carey, Mark; DiSalvo, W.; Williams, Ian; Rigas, James R.; Dmitrovsky, Ethan

doi:10.1200/jco.2005.23.16_suppl.7093

Cited by 2 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Combining the EGFR-TKI erlotinib with bexarotene induced at least additive suppression of growth and cyclin D1 expression in retinoic acid (RA)-resistant human bronchial epithelial cells that had silenced RAR-β and in some lung cancer cell lines. A phase I trial of erlotinib and bexarotene was conducted in patients with www.TheOncologist.com advanced aerodigestive tract cancers, including NSCLC [29]. Twenty-four patients were enrolled, including 46% women and 79% with NSCLC.…”

Section: Combining Targeted Agentsmentioning

confidence: 99%

Combining Targeted Therapies and Drugs with Multiple Targets in the Treatment of NSCLC

Maione

Gridelli

Troiani³

et al. 2006

The Oncologist

View full text Add to dashboard Cite

The first generation of clinical trials of targeted agents in non-small cell lung cancer (NSCLC) treatment has concluded. To date, only a few of these new agents can offer hope of a substantial impact on the natural history of the disease. Nevertheless, clinically meaningful advances have already been achieved. In chemotherapy-refractory advanced NSCLC patients, gefitinib and erlotinib, two epidermal growth factor receptor tyrosine kinase inhibitors, represent a further chance for tumor control and symptom palliation. In chemotherapy-naive, advanced, nonsquamous NSCLC patients, the combination of the anti-vascular endothelial growth factor monoclonal antibody bevacizumab with chemotherapy was demonstrated to produce better survival outcomes than with chemotherapy alone. The relative failure of first-generation targeted therapies in lung cancer may be a result of multilevel crossstimulation among the targets of the new biological agents. Thus, blocking only one of these pathways allows others to act as salvage or escape mechanisms for cancer cells. Preclinical evidence of the synergistic antitumor activity achievable by combining targeted agents that block multiple signaling pathways has recently been emerging. Clinical trials of multitargeted therapy may represent the second generation of studies in this field, and some of these are already ongoing. In a recent phase I/II trial, the combination of erlotinib and bevacizumab demonstrated very promising activity in the treatment of advanced NSCLC pretreated with chemotherapy. Whether the multitargeted approach is best performed using combinations of selective agents or agents that intrinsically target various targets is a matter of debate.

show abstract

Section: Combining Targeted Agentsmentioning

confidence: 99%

Combining Targeted Therapies and Drugs with Multiple Targets in the Treatment of NSCLC

Maione

Gridelli

Troiani³

et al. 2006

The Oncologist

View full text Add to dashboard Cite

show abstract

“…Preliminary results were reported, with a median survival of 5 months, estimated 1-year survival of 13%, and improvement or no decline in QoL in 67% of patients (Table 2) [57]. A combination trial with the agent and erlotinib is also underway [58].…”

Section: Bexarotenementioning

confidence: 96%

Second- and third-line treatments in non-small cell lung cancer

Kumar¹,

Wakelee²

2006

Curr. Treat. Options in Oncol.

View full text Add to dashboard Cite

Slow but steady progress has been made in the treatment of advanced non-small cell lung cancer. For first-line therapy, multiple chemotherapy combination therapies can extend survival and improve quality of life. And recently, for the first time ever, a noncytotoxic agent, the antivascular endothelial growth factor antibody bevacizumab, has been shown to improve survival when added to chemotherapy. Striking improvements have also been made in second-line treatment. In August 2004, only one agent was US Food and Drug Administration (FDA) approved in this setting, docetaxel, but by the beginning of 2005, two more were available, pemetrexed and erlotinib. All three of these drugs can significantly benefit patients, with 1-year survival in excess of 30%. Choosing between the three agents can be challenging, and this review focuses on the toxicity differences and predictors of response that can help guide this decision. Docetaxel and pemetrexed, both traditional intravenous cytotoxins, are excellent options for patients who have shown some response to first-line chemotherapy, but at this time, no other means exist to determine likelihood of response. When choosing between the two, pemetrexed causes significantly less neutropenia than does docetaxel, at least on the standard every-3-week regimen. With erlotinib, an oral epidermal growth factor receptor (EGFR) inhibitor, there are factors that can predict for response, including little or no smoking history, and adenocarcinoma histology. Therefore, patients who fit these characteristics are good candidates for second-line erlotinib. However, the relationship between response to erlotinib and improved survival remains unclear, and several laboratory analyses that may help further, such as evaluation of EGFR gene copy number, are still under development. Although erlotinib is the only FDA-approved option currently available for third-line therapy, many patients with good performance status may benefit from third-line therapy and beyond. In addition to the approved second-line options, other single-agent chemotherapies to consider for treatment beyond second-line are gemcitabine, irinotecan, and oral topotecan. Many new drugs, including bevacizumab, ZD6474 (AstraZeneca, Wilmington, DE), sorafenib, cetuximab, paclitaxel poliglumex, epothilones, and others, alone or in combination with traditional agents, are currently undergoing investigation and hold great promise.

show abstract

A phase I trial of erlotinib and bexarotene as a targeted combination therapy for aerodigestive tract cancers

Cited by 2 publications

References 0 publications

Combining Targeted Therapies and Drugs with Multiple Targets in the Treatment of NSCLC

Combining Targeted Therapies and Drugs with Multiple Targets in the Treatment of NSCLC

Second- and third-line treatments in non-small cell lung cancer

Contact Info

Product

Resources

About