ISTANBUL, Turkey--A phase III
multicenter study has confirmed that
high tumor tissue expression of the gene
ERCC1 in patients with metastatic nonsmall-
cell lung cancer (NSCLC) is predictive
of resistance to cisplatin. In
the study, Rafael Rosell, MD,
PhD, and his coinvestigators
customized therapy to doublets
with or without cisplatin,
based on patients' levels
of ERCC1 expression.
The findings are important
in that they could enable clinicians
to identify patients more likely to
do well on cisplatin and, conversely, potentially
would alert them to subsets of
NSCLC patients in whom non-cisplatinbased
regimens might be more effective,
with the added benefit that these patients
could avoid toxic side effects of an agent
unlikely to be helpful.
The 444-patient trial was presented at
the 31st Congress of the European Society
for Medical Oncology (ESMO) (Late
Breaking Abstract 1). ERCC1 (excision
1), a nucleotide excision
repair gene, has been associated
with resistance to cisplatin,
said Dr. Rosell, scientific
director for oncology
research, Catalan Institute of
Oncology, Barcelona, Spain. Dr.
Rosell, with colleagues from the University
of California at Davis Cancer Center
and the Spanish Lung Cancer Group,
conducted the trial at 24 study sites.
Before treating the patients, the researchers
isolated ERCC1 mRNA from
biopsies of their tumors, and then used
quantitative real-time reverse transcriptase
PCR to assess ERCC1 expression
Patients were then randomized in a
1:2 ratio to a control arm, in which they
received chemotherapy with docetaxel
(Taxotere) and cisplatin, or to a genotypic
arm, in which patients with low
ERCC1 expression received docetaxel/
cisplatin as in the control arm, but those
with high ERCC1 expression were treated
with docetaxel and gemcitabine (Gemzar).
A total of 366 patients completed
the study; all were evaluable for progression-
free and overall survival, and 346
were evaluable for overall response.
In the control arm, 53 patients (39.3%)
had a response to treatment (95% CI
31.4% to 47.8%). Response to chemotherapy
was significantly higher in the
genotypic (ERCC1-expression stratified)
arm, with 107 patients (50.7%) achieving
a response (95% CI 44% to 57.5%,
P = .019).
"Patients in the control arm with high
levels of ERCC1 would have done better
with the docetaxel/gemcitabine regimen,"
Dr. Rosell said.
The results, he concluded, "provide a
proof-of-principle for the practicality and
usefulness of tailoring chemotherapy for
individual patients," and also provide a
path for future research into chemotherapy
customization in patients wtih