30 september 2011: Bron: Cancer Prev Res (Phila). 2011 Jul;4(7):984-93.

Nadat in 2005 studies naar effect van celebrex - celecoxib waren stilgelegd wegens vermeende risico op hartfalen zijn er toch weer studies gedaan nadat bleek dat het risico op hartfalen niet opwoog tegen het eventuele profijt van celebrex - celecoxib bij longkanker. De meest recente studie toont ook aan dat celebrex longkanker kan voorkomen bij rokers en vroegere rokers. Hier het abstract van de studie, daaronder een studie uit 2004 met celebrex bij longkanker patienten met ook positieve resultaten:

Cancer Prev Res (Phila). 2011 Jul;4(7):984-93.

Lung cancer chemoprevention with celecoxib in former smokers.

Mao JT, Roth MD, Fishbein MC, Aberle DR, Zhang ZF, Rao JY, Tashkin DP, Goodglick L, Holmes EC, Cameron RB, Dubinett SM, Elashoff R, Szabo E, Elashoff D.

Source

Pulmonary and Critical Care Section, New Mexico VA Health Care System/University of New Mexico, Albuquerque, New Mexico 87108, USA. jenny.mao@va.gov

Abstract

Ample studies suggest that the cyclooxygenase-2 (COX-2)/prostaglandin E(2) (PGE(2)) pathway plays a pivotal role in carcinogenesis and that COX-2 inhibition may help prevent lung cancer. Therefore, we conducted a randomized, double-blind, placebo-controlled trial of the COX-2-selective inhibitor celecoxib (400 mg bid for 6 months) in former-smokers (age ≥ 45, ≥ 30 pack-years of smoking, ≥ 1 year of sustained abstinence from smoking). We assessed the impact of celecoxib on cellular and molecular events associated with lung cancer pathogenesis; the primary endpoint was bronchial Ki-67 labeling index (Ki-67 LI) after 6 months of treatment. Of 137 randomized subjects, 101 completed both baseline and 6-month bronchoscopies and were evaluable for the primary endpoint analysis. The beneficial effect on Ki-67 LI was greater in the celecoxib arm (versus placebo) in a mixed-effects analysis (P = 0.0006), and celecoxib significantly decreased Ki-67 LI by an average of 34%, whereas placebo increased Ki-67 LI by an average of 3.8% (P = 0.04; t test). In participants who crossed over to the other study arm at 6 months (all of whom had received 6 months of celecoxib at the end of a 12 months treatment period), the decreases in Ki-67 LI correlated with a reduction and/or resolution of lung nodules on computed tomography. Celecoxib significantly reduced plasma c-reactive protein and interleukin-6 mRNA and protein and increased 15(S)-hydroxy-eicosatetraenoic acid levels in bronchoalveolar lavage (BAL) samples. The baseline ratio of COX-2 to 15-hydroxyprostaglandin dehydrogenase mRNA in BAL cells was a significant predictive marker of Ki-67 response to celecoxib (P = 0.002). Our collective findings support the continued investigation of celecoxib for lung cancer chemoprevention in former smokers at a low risk of cardiovascular disease.

Comment in

Cancer Prev Res (Phila). 2011 Jul;4(7):949-53.

PMID:: 21733822; [PubMed - in process]
PMCID: PMC3153413: [Available on 2012/7/1]

In een studie met 26 patiënten zorgde het ontstekingsmiddel Celebrex dat normaal gesproken gebruikt wordt bij vormen van athrose voor een bijzonder positief effect nadat het als aanvulling werd gegeven bij chemo bij longkankerpatiënten. Bij maar liefst 5 van de 26 patiënten verdween de kanker volledig (= 19%) terwijl normaal een percentage van 5 % wordt gemeten bij alleen chemo. Volgens Dr. Altorki, directeur van de afdeling thoraxchirurgie van het New York-Presbyterian Hospital’s Weill Cornell Medical Center zijn deze resultaten in het verleden nog nooit gezien. Celebrex wordt gezien als een Cox-2 remmer (inhibitor) en daar worden wereldwijd honderden studies naar verricht. Celebrex onderdrukt bij athrose de aanmaak van prostaglandin, een stofje dat algemeen gezien wordt als een stimulator van kankergroei. In feite blokkeert celebrex de energietoevoer naar de kankercel en stimuleert zelfs het apoptoseproces (zelfmoord kankercel). Hoewel er nog veel onderzoek naar gedaan zal worden is dit toch een bemoedigend resultaat. Cox-2 remmers (inhibitors) werken overigens niet alleen bij longkanker, maar bij vele soorten kanker zoals melanomen, prostaatkanker enz. enz. Ook is dit een positief bericht omdat deze studie al bij patiënten een goed resultaat geeft. Phase III studies kunnen en worden nu dan ook opgezet. Hieronder het persbericht zoals dat op ASCO werd vrijgegeven.

The popular painkiller Celebrex may help to curb the growth of deadly lung cancers, a small preliminary trial suggests. The study is the latest to hint that the anti-inflammatory pills taken by millions of American for arthritis can play a role in preventing a variety of cancers — or even curing them.

IN THE NEW study, lung tumors completely disappeared in five of 26 patients with lung cancer who took Celebrex in addition to their standard chemotherapy regimen, reported Dr. Nasser Altorki, director of thoracic surgery at New York-Presbyterian Hospital’s Weill Cornell Medical Center.
That translates to a 19 percent tumor-eradication rate, compared to the 5 percent rate traditionally seen with chemotherapy alone, he said.
“This is very encouraging,” Altorki said. “Historically we haven’t seen these kind of results.”
Others agreed. “Within the limitations of [a preliminary] trial, this is interesting and exciting data,” said Dr. Michael Gordon, associate dean for research for the University of Arizona Health Sciences Center in Phoenix.
Altorki is the first to admit that, taken alone, the study is too preliminary to draw any firm conclusions. But it is just one of several recent trials showing that combining chemotherapy with Celebrex or similar drugs appears to be synergistic in fighting cancer, noted Dr. Bernard Levin, vice president of cancer prevention at M.D. Anderson Cancer Center in Houston.

The approach is so promising that more than 100 clinical trials are now underway to see if the anti-arthritis drugs — collectedly known as COX-2 inhibitors — may help prevent and treat cancers of the lung, colon, pancreas, prostate and more, Levin said.

BLOCKING CANCER GROWTH
Scientists still aren’t exactly sure how the COX-2 inhibitors — a class of drugs that in addition to Celebrex includes Vioxx and several other agents — combat cancer, but dozens of lab and animal studies have provided some powerful hints, Altorki said.
First, they may choke off the supply of nutrients to tumors, thereby killing them, he said. Additionally, they appear to boost the body’s immune response and encourage cancer cells to self-destruct.
As their name implies, COX-2 inhibitors block production of a chemical called COX-2, which triggers the pain and inflammation that characterize arthritis. Too little COX-2, in turn, shuts down the body’s production of prostaglandins, substances that cause inflammation and may also fuel tumor growth.

“Tumors make a lot of prostaglandin, a substance that acts as a very powerful tumor promoter,” Altorki said. “Prostaglandin brings in new blood vessels to feed tumors. This somehow masks them from the immune system and turns off the built-in mechanism that tells cancer cells to self-destruct when they become old, hurt or defective.”

Turning off prostaglandin production not only deprives the tumor of the blood supply it needs to grow, but also restores the built-in suicide mechanism in the cells, Altorki said. “And in doing so, this somehow restores the immune system whose function is to fight disease.”
One of the most exciting aspects of the approach, he said, is that it targets a pathway shared by almost all cancers.

Also noteworthy is the drugs’ safety profile, Levin said, explaining that the COX-2 blockers were designed to be gentler on the stomach than aspirin and other arthritis drugs. In fact, there is some indication that they may even ameliorate some of the arthritis-like side effects that accompany chemotherapy, such as debilitating joint pain, he said.
Already, early studies of the COX-2 blockers in people with a hereditary disease that predisposes them to precancerous growths of the colon were so persuasive that the U.S. Food and Drug Administration OK’d their use for these patients. Three large studies involving over 5,000 volunteers to see if Celebrex and Vioxx can help prevent colon cancer in healthy people as well are underway, with results expected within two years.
As for lung cancer, the hope is that by turning down COX-2 production, cancer cells’ coat of armor will be penetrated, making them more prone to killing by chemotherapy.

LUNG CANCER TRIAL
The new study, presented here Tuesday at the annual meeting of the American Society for Clinical Oncology, was designed to see what happens if patients with cancer still confined to the lung were given Celebrex in addition to traditional chemotherapy prior to surgery to remove the tumor. The study was funded by Pharmacia, which makes Celebrex, and Pfizer, which helps to market it.
This year, an estimated 170,000 Americans will be diagnosed with lung cancer, 155,000 of whom will die — more than from breast, prostate and colon cancer combined.