Clinical Validation of Cell Culture Assays

[gpawelski]

Gemzar is already approved as a cancer drug in the treatment for non-small cell lung cancer, pancreatic cancer and metastatic breast cancer. Clinical studies reviewed by the FDA showed that patients treated with a combination of Gemzar and carboplatin experienced a significant improvement in survival and response rates compared to carboplatin alone.

Clinical Oncologists for Individualized Treatment of cancer patients have found out years ago that the combination of gemcitabine + platinum (either cisplatin, carboplatin or oxaliplatin) was the most important drug combination introduced for the treatment of solid tumors in the past 18 years. Clinical responses with this regimen were unprecedented.

Individualized testing of the gemcitabine + platinum combination began in the mid-1990s by Dr. Robert Nagourney, Director of Rational Therapeutics, Inc., a cell culture assay laboratory in California. Many patients have received treatment with this regimen because of cell culture assay testing long before any clinical trials in their particular disease types had ever been published.

Cell culture assay's contribution in terms of recognizing the synergistic effects of this combination had been very important in getting clinical trials with this regimen started in a broad spectrum of cancers. Many thousands of lives had been saved, long before these clinical trials ever started.

Results from Rational Therapeutics' EVA cell culture assay test have been shown in published studies to correlate with patient response, time to progression and survival. Clinically validated drug testing assays hold much promise as a means to guide drugs through the Phase I-Phase II transition, which is an especially costly and time consuming part of the drug development process.

The Todd Cancer Institute at Long Beach Memorial Medical Center is the first cancer program in the nation to apply laboratory-directed therapy as the first-line treatment for advanced solid tumors. The Center is currently hosting clinical trials for cancers of the lung, colon, stomach, pancreas and prostate.

http://www.rational-t.com/

Chemotherapy Delays Pancreatic Cancer Recurrence

Chemotherapy may help pancreatic cancer patients live longer before their disease returns.

New research from Germany reveals using the drug gemcitabine (Gemzar) can significantly delay the recurrence of pancreatic cancer compared to no chemotherapy after a patient has surgery for the disease.

Researchers compared gemcitabine to no anticancer drug therapy in 368 patients who had surgery to remove pancreatic cancer. With a follow-up of about four-and-a-half years, results reveal recurrent cancer developed in 74.3 percent of the gemcitabine group and 92 percent in the control group.

Patients in the study who took gemcitabine lived an average of 13.4 months without their cancer coming back compared to 6.9 months in patients who did not take the drug. At three and five years into the study, the estimated disease-free survival was 23.5 percent and 16.5 percent in the gemcitabine group compared to 7.5 percent and 5.5 percent in the control group, respectively. There was no difference in overall survival.

Pancreatic cancer is the fourth leading cause of cancer death in the United States with an overall survival rate of less than 4 percent. Surgery is the best hope for long-term survival, but the disease still returns in most cases.

SOURCE: The Journal of the American Medical Association, 2007;297:267-277

[gpawelski]

Medicare Contractor Establishes Reimbursement Coverage Policy for Cell Culture Assay Tests

National Heritage Insurance Company (NHIC), the contractor that administers Medicare programs in California, has established a positive coverage policy for Cell Culture Assay Tests known as Chemosensitivity (Resistance) Testing for a tumor specimen from a Medicare patient obtained anywhere within the United States, but submitted for testing by one of the approved laboratories located within California. Medicare bills for Chemosensitivity (Resistance) Testing are billed through NHIC because the test is conducted by the approved laboratories in California.

The Chemosensitivity (Resistance) Test can help see what treatments have the best opportunity of being successful for "high" risk cancer patients. The test measures the response of "live" tumor cells to drug exposure. Following this exposure, the assays measure both cell metabolism and cell morphology (Functional Profiling). The integrated effect of the drugs on the whole cell, resulting in a cellular response to the drug, measuring the interaction of the entire genome. Assays based on "cell-death" occur in the entire population of tumor cells.

This cell culture assay technology has been clinically validated for the selection of optimal chemotherapy regimens for individual patients. It is a laboratory analysis based on tumor tissue profiling that uses "fresh" human tumor biopsy or surgical specimen to determine which drugs or combinations of chemotherapeutic agents have the highest likelihood of response for individual cancer patients.

Following the collection of "fresh" tumor cells obtained from surgery or tru-cut needle biopsies, a cell culture assay is performed on the tumor sample to measure drug activity (sensitivity and resistance). This will pinpoint which drug(s) are most effective. Tissue, blood, bone marrow, and ascites and pleural effusions are possibilities, providing tumor cells are present. At least one gram of fresh tissue is needed to perform the tests, and a special kit is obtained in advance from the lab.The treatment program developed through this approach is known as assay-directed therapy.

Individualized assay-directed therapy is based on the premise that each patient's cancer cells are unique and therefore will respond differently to a given treatment. This is in stark contrast to standard or empiric therapy, which chemotherapy for a specific patient is based on average population studies from prior clinical trials.

The decision had been made that the assay is a perfectly appropriate medical service, worthy of coverage on a non-investigational basis. What is of particular significance is that they abandoned the artificial distinction between "resistance" testing and "sensitivity" testing and are providing coverage for the whole FDA-approved kit. Drug "sensitivity" testing is merely a point a little farther along on the very same continuum which "resistance" testing resides.

Cell cuture assay tests based on "cell-death" have proven very effective in identifying novel treatment combinations for a variety of cancers. The value of cell-death assays is that they can and do accurately predict clinical outcomes and define novel chemotherapeutic synergies. It can help see what treatments will not have the best opportunity of being successful (resistant) and identify drugs that have the best opportunity of being successful (sensitive).

The current clinical applications of in vitro chemosensitivity testing is ever more important with the influx of new "targeted" therapies. Given the technical and conceptual advantages of "functional profiling" of cell culture assays together with their performance and the modest efficacy for therapy prediction on analysis of genome expression, there is reason for renewed interest in these assays for optimized use of medical treatment of malignant disease.

The payment provided will be sufficiently realistic that all Medicare patients for whom this testing is indicated will be able to get it with only the routine 20% co-payment, as Medi-gap insurance secondaries are mandated to provide payment for co-pays for Medicare-approved services.

The coverage became effective for claims for services performed on or after February 28, 2007. The decision is posted at:

http://www.medicarenhic.com/cal_prov/policies.shtml

http://www.medicarenhic.com/cal_prov/articles/chemoassaytest_0107.htm