Chemoresistance and Chemosensitivity Testing in the Selection of Second Line Anti Neoplastic Drug Delivery

A number of retrospective and fewer prospective reports have suggested the potential for in vitro testing of ovarian cancer tumor samples to select treatment, particularly in the setting of recurrent or resistant disease.31-33 The goal of all such testing would be to provide the clinician with a tool that will permit the delivery of a treatment strategy that is more likely to be beneficial, compared with empiric decisions regarding treatment based on evidence-based (and other) clinical data, and good clinical judgment.34,35

Before briefly discussing the evidence supporting the clinical usefulness of these claims, it is important to appreciate the critical distinction between a prognostic and a predictive test in the oncology arena.

A prognostic test provides information regarding the statistical likelihood of a more or less favorable outcome. For example, women with advanced-stage or high-grade ovarian cancer are more likely to have a poorer survival outcome compared with individuals with early-stage or low-grade disease. This is an example of a prognostic test, since there is nothing in the information that permits the clinician to specifically select a treatment program that can actually improve that survival.

In contrast, a predictive test provides data that allow the clinician to use the information to select a particular management strategy that has been shown to enhance the opportunity for a more favorable outcome. Excellent examples of predictive tests in oncology are the estrogen receptor, which suggests the potential utility of hormonal therapy, and Her2 overexpression, which predicts the activity of treatment containing trastuzumab.

Unfortunately, to date, the only available evidence reveals several of these che-mosensitivity or chemoresistance assays to be of possible prognostic value in ovarian cancer.34,35 For example, an ovarian cancer shown to be highly resistant to a number of chemotherapeutic agents may have a particularly poor outcome, but there is currently no prospective evidence that the active selection of a particular drug (e.g., low level of resistance or suggested high degree of sensitivity in vitro), based on an assay result, will improve the chances for a favorable outcome (again, compared with the judgment of an experienced oncologist).

It is hoped that future trials in this general area will be able to either establish the clinical utility of one (or more) of these assay systems or continue to reveal them to be solely of prognostic (and therefore quite limited) clinical value in this setting.

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