Subj: Resistance Testing (cell proliferation) vs Sensitivity Testing (cell death)
Date: 8/3/2002 10:33:43 AM Pacific Daylight Time
From: an oncologist writing from aol.com
To: mail@weisenthal.org

The key word today (apoptosis) regarding assays seems to be "cell death" assays. What is the difference between a "cell death" assay [CCRT] and a "cell proliferation" assay [EDR] for predicting resistance to chemotherapy since that is what Medicare now seems to pay for. Why is one type (cell death vs cell proliferation) preferred over another? With ongoing discussions regarding the use of assays, resistance or sensitivity, continuing to appear (your letter to editor in ONCOLOGY especially), what is it going to take before the appropriate clinical trials are done to answer the question of utility once and for all in an acceptable format for the medical oncology community.

Thanks, Tom

My reply:

Subj: CCDRT Q's Date: 8/3/2002 1:45:12 PM Pacific Daylight Time
From: mail@weisenthal.org
To: oncologist Tom (aol.com )

Medicare pays for BOTH cell death assays and cell proliferation assays. Details are given at the following web URL:

nb: as I said in the paper, the distinction between "resistance" assays and "sensitivity" assays is entirely semantic. I prefer the generic term "drug resistance assay" for both.

With Robert Nagourney, I was the co-founder (in 1985) of Oncotech. I was the laboratory director until 1992. I supervised over 10,000 cell proliferation (thymidine incorporation) assays. You can read a detailed head to head comparison of the different labs and technologies at the following URL:

http://weisenthal.org/faqw.htm

This (above URL) also addresses the issue of clinical trials. My conscience is clear that I did everything possible to get the (randomized) trials done. I hope to prove that assay directed therapy is superior to empiric, protocol therapy before I die. I'm willing to do the assays, but I'll never have enough money to fund the trials myself. Among other things, all of this is non-proprietary, public domain technology. All of it.

Let's say I take out a bank loan for $5,000,000 to do a trial of assay directed adjuvant therapy of breast cancer. We accrue the patients, follow them 10 years and we prove superiority of assay directed therapy. Two problems (from my point of view)...100 labs all jump in and take advantage of 25 years worth of hard work and all that money and just start competing against me...no problem... I welcome this, but who's going to lend me the $5,000,000 with this as the probable outcome?

Problem number 2 is that empiric, protocol therapy will doubtless change during this time. So Maurie Markmann will then say that the trial wasn't relevant to "today's" (year 2010) therapy.

As I said; I'm totally willing to do it. I actually got two very large, prospective, randomized trials (myeloma and NSCLC) approved and funded and started in the late 80s. But the trials were closed within 8 months for poor accrual and protocol violations in the STANDARD TREATMENT arm which had absolutely nothing to do with the assays! Since then, I (and Nagourney) have tried to get trials done through virtually all of the cooperative groups, from the CCSG to the GOG. No one will do it unless we pay for it...Catch 22.

The medical oncology community is going to be dragged, kicking and screaming, into this; totally against its will, because it works and because patients will demand it. At a certain point, when unable to ignore and bury it any longer, the medical oncology community will itself organize the trials, just to "prove" me wrong and shut me up. Then we'll all realize how we've wasted the last 20 years doing all those entirely pointless prospective randomized trials of Pepsi Cola vs. Coca Cola.

Thank you very much for taking the time to write; I do hope that you will look up the referenced URLs and please write again if you have other questions, criticisms, and/or suggestions.

- Larry Weisenthal Huntington Beach, CA 714-894-0011 (phone)