In Elderly Lung Cancer Patients, All-Biologic Regimen Found To Be Efficacious And Well-Tolerated
Main Category: Lung CancerAlso Included In: Seniors / Aging
Article Date: 03 Aug 2009 - 0:00 PDT
Previously untreated non-small cell lung cancer (NSCLC) patients over the age of 70 respond well to a combination of bevacizumab and erlotinib, Fox Chase Cancer Center researchers reported at the annual meeting of the International Association for the Study of Lung Cancer.
"Based on our initial data, the combination appears to be well tolerated and efficacious, though we'll have to wait and see the final results," says Hossein Borghaei, D.O., medical oncologist at Fox Chase, who led the trial.
Elderly patients are often excluded from clinical trials because researchers fear they will have trouble tolerating standard chemotherapy regimens. That leaves open the question of how best to treat these individuals who account for more than half of all NSCLC in the United States.
With that challenge in mind, Borghaei and colleagues designed a trial testing a combination of two molecularly targeted agents in patients 70 years or older. The team reasoned that a combination lacking standard cytotoxic agents may be better tolerated by these patients, potentially without comprising efficacy. "We looked for a regimen that had few side effects, would involve only targeted agents, and had a bit of a track record. This combination was a natural fit," Borghaei says. Several small phase II trials in younger NSCLC patients demonstrated that the combination had anti-tumor activity and a relatively favorable toxicity profile.
Thus far 21 elderly NSCLC patients have enrolled in the Fox Chase trial and 14 are evaluable for response. The median age of the 14 evaluable patients is 78, with a range of 71 to 84 years. Four patients have had partial responses with demonstrable tumor shrinkage and three patients had stable disease by RECIST criteria.
The combination appears safe and well tolerated in this patient population with the most commonly encountered toxicities of clinical relevance being high blood pressure, fatigue, loss of appetite and diarrhea.
"The observed activity of this regimen in this patient population suggests promise and therefore warrants continued investigation," Borghaei says. He also emphasizes that designing a clinical trial just for elderly patients is a novel approach, but one that should be used more in the future given the large proportion of NSCLC patients in this demographic group.
Source:
Diana Quattrone
Fox Chase Cancer Center
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Targeted Drug Combos Could Outsmart Cancer
posted by Gregory D. Pawelski on 5 Aug 2009 at 7:19 amThis is a perfect example that it would be more advantageous to sort out what's the best "profile" in terms of which patients benefit from this targeted drug or that targeted drug. The short term future of cancer therapeutics is combinations of targeted drugs. Can they be combined? What's the proper way to work with all the new targeted drugs? However, what's good for the group (population studies) may not be good for the individual. If a targeted drug combination works extremely well for a certain percentage of cancer patients, identify which ones and "personalize" their treatment.
Patients would certainly have a better chance of success had their cancer been chemo-sensitive rather than chemo-resistant, where it is more apparent that targeted therapy would improve the survival of patients, and where identifying the most effective targeted therapy would be more likely to improve survival above that achieved with "best guess" empiric therapy through clinical trials.
Avastin may have the potential to improve the efficacy of targeted therapy. The combination of Avastin with other targeted therapy may be promising, particularly with regard to safety and efficacy. Tumor growth is dependent on angiogenesis. Angiogenesis is dependent on vascular endothelial growth factor (VEGF). Anti-angiogenesis drugs like Avastin work by block the activity of VEGF to prevent the growth of new capillaries into the tumor and thereby sustain tumor growth.
Avastin directly binds to VEGF to directly inhibit angiogenesis, by choking off the blood vessels that provide a tumor with oxygen and nutrients. Tumors which secrete relatively low levels of VEGF, might be more susceptible to an agent like Avastin which works by blocking VEGF (its effects upon endothelial cells which make up blood vessels).
In cell culture analysis, which actually assesses the direct or indirect effect of a drug upon the cell, whether it is a tumor cell or an endothelial cell, VEGF happens to be the molecule which has been implicated in the process of Avastin on endothelial cells. Drugs like Avastin have striking anti-microvascular effects but minimal anti-tumor effects. That is the reason giving Avastin with combination anti-tumor agents.
Sutent is a "multi-targeted" kinase inhibitor. That means it inhibits several proteins involved in triggering replication in cancer cells. Until Sutent, you had to take one type of drug for "anti-tumor" effects of human neoplasms, and another drug for "anti-microvascular" effects. With Sutent, multiple proteins are involved in both tumor proliferation (growth) and angiogenesis (blood vessels feeding a tumor). It has has both "anti-tumor" as well as "anti-angiogenic" properties. In addition, because it inhibits "multiple" kinases, it possesses activity against "multiple" types of tumors.
Physicians may have to combine several targeted treatments to try an achieve cures or durable reponses for more complicated tumors like those that occur in the breast, colon and lung. The trick is figuring out which patients will respond, and the challenge is to figure out which patients to give these drugs to.
In cancer medicine, it's not a case of throwing targeted drugs at the problem. It's knowing "what" targeted drugs and "how" to use them in "individual" patients (not average populations). It would be more beneficial to assess the net effect of all targeted processes.
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