One-Two Punch for Lung Cancer
(Ivanhoe Newswire) -- UCLA researchers find adding the COX-2 inhibitor Celebrex (celecoxib) to the lung cancer drug Tarceva significantly increases the number of people who can benefit from the therapy
In their study, about 33 percent of patients responded to the combination treatment. Typically, only about 10 percent of lung cancer patients respond to Tarveca alone.
The addition of Celebrex is believed to up the efficacy of Tarceva because it inhibits the COX-2 cell signaling pathway. That pathway has been linked to resistance to Tarveca, which blocks the growth of tumor cells by targeting a protein known as the epidermal growth factor receptor, or EGFR.
"Tarceva alone is a great drug and has a lot of clinical benefits, but for a small proportion of patients," says study author Dr. Karen Reckamp. "With this drug combination, we saw an increase in response rates, indicating we are overcoming some resistance."
All of the participants in the study were diagnosed with advanced lung cancer that failed to respond to conventional treatments like chemotherapy.
The authors note the Tarceva-Celebrex treatment could be superior to chemotherapy because it targets only the diseased cells. Chemotherapy kills all fast growing cells, healthy and diseased alike, and can cause serious side effects. In this study, Tarceva only caused minor side effects, such as rash and diarrhea, and the addition of Celebrex didn't add any side effects to the mix.
The researchers plan more study to confirm these early findings and delve more deeply into why some people are resistant to Tarveca.
SOURCE:
Clinical Cancer Research, published online June 1, 2006
: Clin Cancer Res. 2006 Jun 1;12(11):3381-8.
A phase I trial to determine the optimal biological dose of celecoxib when combined with erlotinib in advanced non-small cell lung cancer.
Reckamp KL, Krysan K, Morrow JD, Milne GL, Newman RA, Tucker C, Elashoff RM, Dubinett SM, Figlin RA.
Authors' Affiliations: Department of Medicine, Division of Hematology/Oncology.
PURPOSE:
Overexpression of cyclooxygenase-2 (COX-2) activates extracellular signal-regulated kinase/mitogen-activated protein kinase signaling in an epidermal growth factor receptor (EGFR) tyrosine kinase inhibition (TKI)-resistant manner. Because preclinical data indicated that tumor COX-2 expression caused resistance to EGFR TKI, a phase I trial to establish the optimal biological dose (OBD), defined as the maximal decrease in urinary prostaglandin E-M (PGE-M), and toxicity profile of the combination of celecoxib and erlotinib in advanced non-small cell lung cancer was done. EXPERIMENTAL DESIGN:
Twenty-two subjects with stage IIIB and/or IV non-small cell lung cancer received increasing doses of celecoxib from 200 to 800 mg twice daily (bid) and a fixed dose of erlotinib. Primary end points included evaluation of toxicity and determination of the OBD of celecoxib when combined with erlotinib. Secondary end points investigate exploratory biological markers and clinical response.
RESULTS: Twenty-two subjects were enrolled, and 21 were evaluable for the determination of the OBD, toxicity, and response. Rash and skin-related effects were the most commonly reported toxicities and occurred in 86%. There were no dose-limiting toxicities and no cardiovascular toxicities related to study treatment. All subjects were evaluated on intent to treat. Seven patients showed partial responses (33%), and five patients developed stable disease (24%). Responses were seen in patients both with and without EGFR-activating mutations. A significant decline in urinary PGE-M was shown after 8 weeks of treatment, with an OBD of celecoxib of 600 mg bid.
CONCLUSIONS:
This study defines the OBD of celecoxib when combined with a fixed dose of EGFR TKI. These results show objective responses with an acceptable toxicity profile. Future trials using COX-2 inhibition strategies should use the OBD of celecoxib at 600 mg bid.
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