Scientists suspect low-dose effects have led to global epidemic
by Gdpawel on Mon Feb 06, 2012 10:40 PM
The Gynecologic Oncology Group (GOG) held its 84th Semi-Annual Meeting on Januray 26-29, 2012 in San Diego, CA.http://www.gog.org/meetinginformation.html Presented last summer, in the first head-to-head clinical trial comparing gene expression patterns (molecular profiling) with personalized cancer cytometric testing (functional profiling or chemosensitivity testing), personalized cancer cytometrics was found to be substantially more accurate.Four different genes were included in the molecular part of the study. The four genes were selected as those which researchers believe to have the greatest likelihood of accurately predicting individual patient response to specific anti-cancer drugs.Although this was the first head-to-head, the accuracy levels found in this trial for personalized cancer cytometric testing were strikingly consistent with those documented in dozens of previous studies, published by respected cancer researchers around the world. In those studies, as in this one, extremely high levels of correlation (in other words, high levels of test accuracy) were found for personalized cancer cytometrics.Source: Arienti et al. Peritoneal carcinomatosis from ovarian cancer: chemosensitivity test and tissue markers as predictors of response to chemotherapy. Journal of Translational Medicine 2011, 9:94.It was hoped that something like this study would be proposed at the semi-annual GOG meeting. Perhaps a good three-armed clinical trial: physician's choice vs molecular profiling vs functional profiling?I understand this issue has been an ongoing saga for some years now. The question that should be addressed is an across the board assessment of the relative accuracy of different endpoints. They should answer all the questions at once, not one followed by another. I hope we do not have to wait until the summer ASCO meeting to find out.
by Gdpawel on Tue Feb 07, 2012 10:50 PM
On ASCO's Connection, a professional networking site for ASCO's worldwide oncology community, Don S. Dizon, MD, FACP posted his take on the semi-annual GOG meeting.He was engaged in updates of ongoing clinical trials and discussion of new trial concepts for ovarian, cervix, endometrial, and other gynecologic cancers. He learned that we are entering a new era in clinical trials—gone are the days of doing a trial in gynecologic cancer using the "next best drug" because it worked in (whatever) cancer. No—the onus on investigators is to design new trials based on science. As Dizon's mentor and friend, Dr. Carol Aghajanian (chair of the Developmental Therapeutics Committee) put it: "No tissue, no marker, no target—no trial." During the meeting, he also found himself considering the endpoints of clinical trials: should it be the response rate? Should it be the proportion of patients who have no tumor growth at six months? Or should it be overall survival? What about quality of life—could this ever be a primary endpoint in clinical trials? What about toxicity as an endpoint? Obviously, the endpoints in a trial depend on the trial itself—phase I studies are geared towards toxicity evaluations, phase II towards effectiveness, and phase III towards survival. It occurred to him—maybe the endpoints should not be determined solely by a group of investigators in a conference hall in San Diego. Maybe it's time to have this dialogue with the public—beyond the National Cancer Institute, beyond the American Cancer Society, beyond ASCO. Maybe they should engage the public into a discussion of what endpoint is "meaningful."I liked the reply to his commentary by Dr. Rick Boulay. Adopting the same endpoints in molecular medicine as they have in the era of cytotoxic chemotherapy, may lead to erroneous conclusions. Reports in the New England Journal of Medicine from ICON 7 and GOG on the use of Avastin (bevacizumab) in frontline ovarian carcinoma have shown modest improvement in disease free interval while overall survival may not be increased.Further teasing out the data shows that shortly after Avastin is discontinued, patients tend to recur. Are they using this drug wrong? Are the expectations of improvement in efficacy despite discontinuation of a biological agent too high?http://connection.asco.org/commentary/article/id/3137/clinic Biologic therapy is on the ascendancy. The possibility of eradicating cancer by selective destruction of tumor blood vessels may represent an attractive therapeutic avenue. It's going to take "combination" antivascular therapy though, to make a difference. The AngioRx Assay is the most promising technology on the therapeutic horizon. And on top of that, putting a vascular disrupting agent in combination with an anti-angiogenesis agent.http://cancerfocus.org/forum/showthread.php?t=3549 http://cancerfocus.org/forum/showthread.php?t=3400
by Gdpawel on Tue Mar 06, 2012 07:19 AM
Dr. Robert Nagourney, of Rational Therapeutics, posted on his blog, his take on the July 2011 meeting of the Ovarian Cancer National Alliance (OCNA), which included a lecture by John Hays, MD, from the National Cancer Institute (NCI), entitled “Decision time: what is the right choice of chemotherapeutic agent(s)?Dr. Hays, part of the molecular signaling section at the NCI, reviewed literature on the topic. He described the need for prospective clinical trials to validate retrospective and in vitro results.He then examined data from three technologies, the Oncotech extreme drug resistance test, Precision Therapeutics ChemoFX test and the ATP-based chemosensitivity test. Dr. Nagourney found it odd that Dr. Hays spent time examining the EDR (extreme drug resistance) technology of Oncotech in as much as it is no longer offered and reflects proliferation-based studies, which have since largely been discredited.http://cancerfocus.org/forum/showthread.php?t=3139 The ATP assay was reviewed using the results of a study published by Dr. Ian Cree in which 180 patients received either assay-directed (ATP) or physician's choice. This study actually provided an improvement for patients who received the ATP-based treatment but failed to achieve significance. It failed largely because it was underpowered.But this reflected a more concerning aspect of the study. It seems that the “physician's choice” arm increasingly applied the best drug regimens developed in Dr. Cree’s own laboratory. As the trial continued to accrue, an increasing proportion of patients received Gemzar (gemcitabine)-based doublets (which were very new at the time) based upon Dr. Cree’s observation of activity for these novel combinations.This had the uncomfortable effect of forcing Dr. Cree to compete with himself. Had Dr. Hays been truly interested in examining this study as Dr. Nagourney has, he might have noticed the good control group response rate partly reflected the application of Dr. Cree’s’ own observations.Indeed, when during Dr. Nagourney's many attempts to conduct a prospective study with the GOG, he was confronted with a study design similar to Dr. Cree’s, (e.g. they could incorporate any treatment they chose, including those that he developed), his statistician demanded that he forego the pleasure, as he could see only too well that the trial had become impossible to power. There was no true control arm for statistical comparison.http://cancerfocus.org/forum/showthread.php?t=748 The final portion of Dr. Hays’ presentation was the ChemoFX assay. This technology propagates tissue biopsies to confluence and then conducts measurement of drug-induced cell death.With substantial funding largely provided by venture capital, Precision Therapeutics has leapt into the GOG with a series of trials. Should this hybrid technology fail to provide prospective results that meet significance, it will be a damaging blow to this unfairly maligned area of investigation.While Dr. Nagourney wishes the ChemoFX investigators luck, a failure on their part could be harmful to the field. Their reliance on propagated, sub-cultured tissues grown to monoculture has been a concern to Dr. Nagourney since they first arose in the last few years as participants in the field.http://cancerfocus.org/forum/showthread.php?t=1114 According to Dr. Nagourney, what is interesting in Dr. Hays’ review is not so much what he said, but what he didn’t say.First, he did not mention the seminal work of Dr. Larry Weisenthal, of Weisenthal Cancer Group, a pioneer in the field.Second, he did not describe the nearly 2,000 retrospective, yet statistically significant correlations in the literature in a wide variety of diseases. He neglected to mention that one of the most widely used regimens for breast and ovarian cancer was developed using the same human tumor culture analyses that he decries. If he actually treats patients, he no doubt uses the cisplatin gemcitabine doublets developed using one of these platforms.Finally, Dr. Hays has failed evidence-based medicine 101. He has forgotten that in life-threatening illnesses where prospective clinical trial data is not available, in accordance with the dictates of evidence-based medicine, one should use the best available data to guide treatments.There is a wealth of data supporting laboratory based drug selection. Presentations like that described do not add to the discourse.http://cancerfocus.org/forum/showthread.php?t=3490
by Gdpawel on Sat May 19, 2012 11:26 PM
It was hoped that something like the Arienti, et al study would be proposed at the semi-annual GOG meeting. Perhaps a good three-armed clinical trial: physicians' choice vs molecular profiling vs functional profiling?
It looks like Dr. Larry Weisenthal of the Weisenthal Cancer Group has given some information in relation to this.
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