Klin Onkol 2000; 13(Speciál2 2000): 1.
New technologies and the rapidly increasing knowledge about the molecular basis of malignant diseases provide important opportunities for the future of chemotherapy. Oncology is used today to treat a whole range of genetically different individuals with similar treatment protocols which are no equally effective for all. Moreover, by a time a cancer cell acquires a metastatic phenotype it has acquired many genetic changes which make it resistant to anticancer drugs. A molecular understanding of the basis of malignant diseases and mechanisms of resistance will allow the cancer to be treated much more effectivelly. We are talking now in this content about individualized chemotherapy in malignant diseases.
The most promising approach for therapy individualization is
nowadays cell culture drug resistance testing (CCDRT). This
human tumor cell assay is a laboratory test performed on fresh
tissue specimens or leukemic blood cell populations. The
procedure includes following stepsi i) isolating tumor cells
from the samples, ii) exposing the tumor cells to drugs during
chort-term culture, iii) assessing drug effects by measuring
either cell proliferation or cell death. There exist hundreds of
publications with dealing the results of CCDRT and their
correlation with therapy outcome and patient survival. One part
of results did not find such a correlation. This is why the
application of CCDRT in clinical oncology has been controversial
in the past. The other part of obtained results is indicating
the associations are highly positive.
The results clearly demonstrate that if the patients are treated
with drugs which are not active in these assays, the patients
die significantly sooner than when they are treated with drugs
which are active in the assays. Moreover, some researchers on
the basis of the results of multi-variate analysis are highly
persuaded, that drug resistance assay results are „far more
important than any other clinical or laboratory prognostic
factor“.
All these findings form the start point for proposal CCDRT to be
a fully-reimbursable, selective, non-investigational service in
malignant diseases diagnosis and treatment. The greatest
progress in this field appeared in the United States. More
recently, it was determined in a Medicare Hearing (Social
Security Administration Docket Number 96-1936, Decision rendered
April 24, 1998) that „By June 30, 1996, Cell Culture Drug
Resistance Testing was sufficiently proven and accepted by the
general medical community to be part of the generally accepted
medical practice. From that time forward it is no longer
considered as experimental“.
In vitro CCDRT like the MTT assay may provide a valuable tool
for prediction of individual therapy outcome. Even there exists
a real need for more examples in in vitro sensitivity correlated
with overall clinical outcome, there exist at least several
reasons or situations in which it could be actually useful. We
are persuaded that patients with relapsed, resistant malignant
diseases, with tumors non responding to usual chemotherapy and
neoplasms where the treatment protocols are not established
today, are the candidates for individualized therapy based on
CCDRT. If nothing else, in the case of in vitro resistance to
selected anticancer drugs, the highly toxic side effects could
be eliminated by avoiding the use of such noneffective agents in
treattment protocols.
