Lay Summary: Chemosensitivity assays are controversial but most experts believe that they do not reliably assist in selecting chemotherapy. There is more evidence for chemoresistance assays but this also remains disputed.
Oncotech ER is a form of chemosensitivity testing, or rather, a modification that tests resistance to chemo rather than sensitivity. The article by Schrag et al1 criticized the field of chemosensitivity and drug resistance, concluding that these types of in vitro assays are not yet ready for prime time. The panel of authors attempted to present evidence that in vitro drug response assays should not be used clinically. This issue was first addressed by an exhaustive Medicare Coverage Advisory Committee (MCAC) in 1999. A panel of physicians selected by the Department of Health and Human Services reviewed hundreds of articles from the literature and heard two days of testimony by experts in the field in an open hearing. The panel voted unanimously that although chemosensitivity assays should not be covered, drug resistance assays should be paid for. This became a cause celebre with a vigorous debate in the literature and variant opinions offered by professional bodies. The American Society of Clinical Oncology vigorously objected and recommended: ”
The use of chemotherapy sensitivity and resistance assays to select chemotherapeutic agents for individual patients is not recommended outside of the clinical trial setting. Oncologists should make chemotherapy treatment recommendations on the basis of published reports of clinical trials and a patient’s health status and treatment preferences. Because the in vitro analytic strategy has potential importance, participation in clinical trials evaluating these technologies remains a priority.” I believe that the So. California branch of ASCO dissented from this recommendation, see http://weisenthal.org/medicareletter.pdf.
The Extreme Drug Resistance Assay (EDR) Assay is a laboratory test performed on a patient’s tumor cells. This lab test is claimed to determine the probability of a tumor’s resistance to a specific chemotherapy drug. If the tumor cells grow in the presence of very high concentrations of chemotherapy drug, then the cancer cells are considered resistant to that drug.
Drug sensitivity and resistance assays have been examined for their potential utility in ovarian cancer by a number of clinical investigators. Unfortunately, analysis of these studies has suffered greatly from the absence of an appropriate control population. The majority of these trials have compared the survival of individuals whose treatment was selected by a particular assay with a historical/retrospective patient group treated at the same institution. A report in the Gynecologic Cancer session described an important attempt by investigators in Europe to directly address the value of the adenosine triphosphate (ATP)-based tumor chemosensitivity assay, by randomizing patients with platinum-resistant ovarian cancer (n = 180) to either “assay-directed therapy” or the treatment of the “physician’s choice”. The objective response rate was 40.5% for the assay-directed group vs 31.5% for the physician’s choice of treatment. Progression-free survival (intention-to-treat analysis) was 104 days in the assay-directed vs 93 days in the physician’s choice groups. In addition, there was no difference in overall survival between the strategies. This study provides support for the conclusion that the ATP-based tumor chemosensitivity assay is not superior to physician’s choice in the selection of chemotherapy in women with platinum-resistant ovarian cancer.Some experts claim that resistance assays are different from chemosensitivity assays and Medicare does cover them. However, this distinction has not been sufficiently demonstrated and most experts vigorously dispute this.
In conclusion, the technologies and the questions that they raise are quite different. It Oncotech Sensitivy testing not yet been recommended by professional societies and gudielines pending completion of a phase III trial. With Oncotech ER the situation is more uncertain, NCCN says that “current evidence is not sufficient to supplant standard of care chemotherapy”.
More recently in ASCO 2008, researchers affiliated with Precision Therapeutics and Columbia University reported that a test of chemoresponsiveness (ChemoFX®) can predict survival of patients with advanced ovarian cancer. This remains something that must be confirmed by future studies. NCCN says that “chemosensitivity.resistance assays are being used in some NCCN centers”, which I consider something less than an endorsement. Thsi si a level 3 recommendations, which is defined as: “The recommendation is based on any level of evidence but reflects major disagreement.”
Schrag D, Garewal HS, Burstein HJ, et al: American Society of Clinical Oncology technology assessment: Chemotherapy sensitivity and resistance assays. J Clin Oncol 22 : 3631 -3638, 2004
John P. Fruehauf In Vitro Drug Resistance Versus Chemosensitivity: Two Sides of Different Coins Journal of Clinical Oncology, Vol 23, No 15 (May 20), 2005: pp. 3641-3643
P. Hwu, A. Y. Bedikian, and E. A. Grimm
Challenges of chemosensitivity testing.
Clin. Cancer Res., September 15, 2006; 12(18): 5258 – 5259.
M. Markman Chemosensitivity and Chemoresistance Testing
J. Clin. Oncol., October 10, 2005; 23(29): 7363 – 7364.
R. Nagourney Chemosensitivity and Resistance Assays: A Systematic Review?
J. Clin. Oncol., May 20, 2005; 23(15): 3640 – 3641.
J. P. Fruehauf and D. S. Alberts
In Vitro Drug Resistance Versus Chemosensitivity: Two Sides of Different Coins
J. Clin. Oncol., May 20, 2005; 23(15): 3641 – 3643.
H. S. Wieand
Chemotherapy Sensitivity and Response Assays: Are the ASCO Guidelines for Clinical Trial Design Too Restrictive?
J. Clin. Oncol., May 20, 2005; 23(15): 3643 – 3644.
M. Castro Resisting a Fundamentalist Policy
J. Clin. Oncol., May 20, 2005; 23(15): 3645 – 3646.