CHICAGO--A role is emerging for multimodality therapy in the
treatment of both resectable and unresectable stage III non-small-cell
lung cancer (NSCLC). When given as an adjunct to radiotherapy or
surgery, chemotherapy can downstage local disease and control
systemic disease spread by eliminating micro-metastases or delaying
the development of metastases, Ann Mauer, MD, a senior fellow in
oncology at the University of Chicago, said at the International
Conference of the American Thoracic Society and American Lung Association.
For unresectable, locally advanced NSCLC, the current treatment
standard is chemotherapy and radiotherapy. A metaanalysis in the British
Medical Journal showed that adding chemotherapy to radiotherapy
increased survival, although the effect was small--less than 4% of
patients were alive at 2 years.
Dr. Mauer said that in a randomized CALGB trial, vinblastine and
cisplatin (Platinol) followed by radiotherapy raised median survival
for patients with unresectable stage III NSCLC from 9.54 months for
radiotherapy alone to 13.74 months for bimodality therapy.
A portion of this trial has been duplicated by CALGB in a three-arm
study of conventional radiotherapy, cisplatin plus radiotherapy, and
hyperfractionated radiotherapy. With a minimum follow-up of 1 year,
this trial of more than 450 patients is showing a significant
increase in survival with chemotherapy plus radiotherapy. Median
survival is 11.4 months for standard radiotherapy, 12.3 months for
hyperfractionated radiotherapy, and 13.8 months for cisplatin plus
radiotherapy. "We are looking forward to longer follow-up to see
if the benefit in survival holds true," Dr. Mauer said.
Another strategy for treating unresec-table stage III NSCLC is
concomitant chemotherapy and radiotherapy, which may allow for an
interaction between the two modalities and enhance local or regional
control of spread of the disease. This approach is promising because
some chemotherapeutic agents may enhance the effects of radiation,
Dr. Mauer said.
Concomitant chemotherapy and radiotherapy is still investigational,
however, she said, because it may increase such side effects as
esopha-gitis and myelosuppression. Doses of chemotherapy given
concurrently with radiotherapy are lower than standard courses of
chemotherapy, and these lower doses may not provide adequate systemic activity.
For resectable stage III NSCLC, two randomized trials have
demonstrated a survival benefit when cisplatin-based chemotherapy
regimens were given before surgery. These trials were small in size,
however, Dr. Mauer said.
A study of 50 patients at M.D. Anderson demonstrated a median
survival of 64 months when surgery followed chemotherapy, compared
with 11 months for surgery alone. A study of 59 patients in Spain
showed a median survival of 26 months with chemotherapy and surgery,
but only 8 months with surgery alone.
Cisplatin and etoposide (VePesid) given concomitantly with
radiotherapy and followed by surgery achieved a median survival of 13
months in patients with stage IIIA NSCLC and 17 months in those with
stage IIIB disease, according to a SWOG investigation. "Bimodal
or tri-modal therapy is potentially superior to resection for local
control and survival, but work still needs to be done to determine
the best approach," Dr. Mauer said.
In particular, researchers need to define the role of surgery in the
combined modality approach. Important issues related to the
sequencing of chemotherapy also need to be resolved, she said. For
example, is sequential chemotherapy better than concomitant? What are
the optimal regimen and duration of therapy?
"Hopefully, with better understanding of the microbiology of the
disease, we can define prognostic factors, predict survival, and
determine whether a patient may or may not respond to a particular
therapy," she said.