The majority of patients with cancer will require treatment with
chemotherapeutic agents at some point in the course of their disease.
Current treatment recommendations rest on carefully designed clinical
studies in large patient populations and provide an individual patient
with a probability for response based on clinically observed response
rates. This approach has led to major progress in clinical oncology and
has helped to identify curative therapeutic regimens for patients with
testicular cancer, some leukemias, some malignant lymphomas, and
childhood tumors.
Successful regimens are now also available for the
adjuvant treatment of patients with breast cancer, osteogenic sarcoma,
cervical cancer, and colorectal cancer. However, there are still a large
number of cancers for which there is only marginal treatment. In
addition, it is becoming clear that each individual patient’s tumor is
genotypically and phenotypically different. Work with the estrogen
receptor or HER 2/
neu has clearly taught us that tailoring
therapy, based on the presence of a receptor or protein in the tumors of
some patients but not in those of others, could improve response rate
(and survival). For these reasons, numerous attempts have been made to
develop in vitro or in vivo assays that might predict individual
response or resistance.
With
predictive assays, there are conceptually a number of problems that are
independent of the type of experimental system used. These include the
choice of drug concentrations relevant for the clinical situation;
intratumor and intertumor (e.g., primary versus metastases or metastases
versus metastases)heterogeneity in tumor(s) from the patient; interference of
experimental conditions with the usual physiologic microenvironment of
tumor cells as they existed in the patient; and selection pressure on
tumor cells by the experimental system used. The relationship between
inhibition of tumor growth in vitro and a patient’s response to
chemotherapy (and survival) is obviously quite complex.
Chemosensitivity
assays only would be helpful in patients with curable diseases
receiving known effective first-line chemotherapy if they had excellent
predictability, allowing for identification of the rare patient with
primary resistant disease. There is no convincing evidence that any
chemosensitivity assay has such a predictive power. However, in the
clinical setting of patients with refractory disease where palliation is
the goal, chemosensitivity assays certainly might help avoid toxic side
effects of agents that are unlikely to be clinically effective.
At
present, there is no convincing evidence that such assay-guided
chemotherapy is superior to a treatment recommendation by an experienced
oncologist with regard to patient survival. There is, however, recent
evidence that clinical response rates may be superior for in vitro
assays-directed chemotherapy versus chemotherapy selected by a
clinician.
lists the various in vitro and in vivo tests that have been used to predict patient response or lack of response. Details on these assays are provided below.
Different Techniques Used for Predictive Tests.