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QUALITY: Is pre-chemo testing the future? by Harvey Frey MD

Careful readers of this blog will have noted that along with reporting about the change in reimbursement for cancer drugs (and to get the real scoop on that you should see JD Klienke’s excellent article in Health Affairs), there’s also been a trend generally in favor of chemo-sensitivity testing before chemotherapy–largely considered a fringe activity by mainstream oncologists. Then this week the NEJM had an article generally in favor of pre-chemo testing. Did the appearance of this article mean that oncologists were moving the way of the pre-chemo testing radicals or did I as the dumb layman misunderstand it? I asked Dr Harvey Frey, who has written for laymen on this subject for THCB before but has generally not been in favor of it, what he thought.

I think you’ve got it right.

Now oncologists guess at prognosis and probable effective treatment based on how a cancer looks under the microscope, how extensive it is when found, and some blood tests. But even within the groups they’ve determined that way, there are still huge variations in actual patient response and survival rates. Since they never know who needs the treatments for sure, many patients are treated who might not need the treatment, and some get ineffective treatments before finding an effective one, and since the treatments are not innocuous, that’s bad.

They first tried doing sensitivity testing by growing cancer cells with different chemotherapeutic agents. For a variety of reasons, that never was very helpful. For years they have thought that, if only they could determine the actual genes responsible for cancer, they could break down the large heterogeneous groups into smaller groups with better defined responses, and spare many patients any treatment at all.

This study is a start toward that end, but still a small step. The technique doesn’t require that they try to grow the cells, but can be done on regular biopsies as obtained now. But so far all it’s shown is a correlation between their test and survival. They haven’t yet shown that they can predict response to hormones or chemotherapy. But there’s every reason to hope that they will ultimately be able to make such predictions, at least with better accuracy than we can now.

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Greg Pawelski
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Greg Pawelski
rondoc
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rondoc

where can a patient go to get the latest functional cell profiling or other useful markers… my wife is on her third chemo and each ct scan shows a new problem but some reduction in others.. don’t know what to do now… time is running out.. help please

Greg Pawelski
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Greg Pawelski

As the Google search engine still brings up this almost four-year-old posting, I am reminded of some of the ideas Dr. Harvey Frey still had of pre-chemo testing (cell culture assays). Most notably is the thought he has that sensitivity testing is done by growing cancer cells with different chemotherapeutic agents. In modern cell culture assays with Functional Tumor Cell Profiling, there is no growing of cells as in the old cell-growth assays. Cells are taken fresh “live” in their three dimensional, floating clusters. Cells are cultured in conical polypropylene microwells for 96 hours to increase the proportion of tumor… Read more »

Gregory D. Pawelski
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Gregory D. Pawelski

Besides the existence of the Chemotherapy Concession (profit motive in drug selection) being one of the major factors working against the individualization of cancer chemotherapy based on testing the cancer biology, the NCI had made an attempt years ago, to study assay-directed therapy of lung cancer on its own. 1. Their expertise was in establishing permanent cell lines and they only tested tumors after first culturing them to amplify their cell number (these were all passaged, grown up, multiplied, replated). The result was that their assay evaluability rate for primary lung cancers was only 11%. 2. The second problem they… Read more »

Gregory D. Pawelski
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Gregory D. Pawelski

Besides the existence of the Chemotherapy Concession (profit motive in drug selection) being one of the major factors working against the individualization of cancer chemotherapy based on testing the cancer biology, the NCI had made an attempt years ago, to study assay-directed therapy of lung cancer on its own. 1. Their expertise was in establishing permanent cell lines and they only tested tumors after first culturing them to amplify their cell number (these were all passaged, grown up, multiplied, replated). The result was that their assay evaluability rate for primary lung cancers was only 11%. 2. The second problem they… Read more »

kim
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Providing us a lots of inrank, isn’t it our duty to spreading that vital purpose to all over proples unaware from health care ?

Arik
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They tell you that a given form of treatment has an above average probability of being associated with a clinical response and/or with being associated with above average survival.

Gregory D. Pawelski
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Gregory D. Pawelski

Dr Ian Cree, Director, Translational Oncology Research Centre, Queen Alexandra Hospital, Portsmouth UK performed the very first prospective, randomized clinical trial of physician’s choice chemotherapy versus ATP assay-directed chemotherapy in non-surgically debulked, platinum-resistant ovarian cancer and presented it at the May, 2005 American Society of Clinical Oncologists (ASCO) meeting in Orlando, Florida. The results were highly suggestive of an effect due to the assay, and the most successful drug regimens used were nearly all developed using the assay. UK results in cancer are always lower than in the US for a variety of reasons. Part of this is probably lead… Read more »

Gregory Pawelski
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Gregory Pawelski

Assay-testing is based on a biological principle that when a drug is effective, it will induce cell-death (apoptosis) in the cancer cell (this is the new technology). If the cancer cell is resistant to a drug, apoptosis will not occur. Assay-testing for apoptosis will determine whether a drug kills the tumor. Chemosensitivity testing (assay-testing) can take the guesswork out of cancer treatment. Currently, physicians select a drug and must wait about six months to see whether it is effective on a particular patient. Conventionally, oncologists rely on clinical trials in choosing chemotherapy regimens. But the statistical results of these population-based… Read more »