2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

adiation alone. Concurrent chemoradiation showed better
results as compared with sequential therapy. Most centers
in Brazil adopt a cisplatin/etoposide concurrent chemoradiation
regimen in this context, although other regimens are
used, such as carboplatin/paclitaxel or cisplatin/vinblastine.
The question of adding additional courses of chemotherapy
after chemoradiation is unsolved.
In a trial performed at the Brazilian National Cancer
Institute, 30 patients with clinical stages IB to IIIA NSCLC
who were candidates for surgical resection received three
cycles of neoadjuvant chemotherapy. Patients without evidence
of progression underwent mediastinoscopy. Those
with negative lymph nodes underwent resection, whereas
radiation was given to those with positive nodes. Twentythree
patients (77%) responded to neoadjuvant chemotherapy,
and complete resection rate was achieved in 21 patients
(70%). 24
For patients with stage IV disease and a good performance
status, chemotherapy is the treatment of choice. With the
exclusion of patients with central nervous system metastasis,
chemotherapy greatly increases survival compared with
best supportive care. 12 This was corroborated by a study of
patients with stage IV NSCLC in a cancer hospital in Sao
Paulo, Brazil. 25 In another trial in three cancer centers in
Brazil, 564 patients with stage IV disease were evaluated.
Of those, 335 (59.4%) received chemotherapy. There was a
great heterogeneity in drug regimens used in the patients.
Again, overall survival was better with chemotherapy compared
with best supportive care. 26
Several agents showed objective responses in advanced
stage NSCLC, including paclitaxel, docetaxel, vinorelbine,
etoposide, pemetrexed, irinotecan, and gemcitabine.
Platinum-containing doublets can lead to 30% to 40% oneyear
survival rates and are superior to single agents. 12
Carboplatin/paclitaxel, cisplatin/vinorelbine, cisplatin/gemcitabine,
carboplatin/docetaxel, or carboplatin/pemetrexate
are drug regimens commonly used in the treatment of
patients with advanced NSCLC in Brazil.
It should be emphasized that in patients with good performance
status and solitary brain metastasis, surgical
resection may improve survival. The results for solitary
metastatic lesions in other sites are controversial. 12
New targeted therapies were shown to produce tumor
responses in patients with advanced lung cancer. Bevacizumab
may be used in combination with paclitaxel and
carboplatin in patients with advanced stage NSCLC with
nonsquamous histology and no hemoptysis. In a metaanalysis
published by investigators from Campinas, Brazil,
bevacizumab improved response rate and progression-free
survival in patients with NSCLC receiving chemotherapy,
while the effect on overall survival was uncertain. 27 Erlotinib
is approved as first-line therapy in patients with EGFR
mutation–positive stage IV NSCLC. It can also be used in
patients who progressed after one prior chemotherapy regimen.
Furthermore, cetuximab showed an increase in overall
survival in patients with stage IV disease when given in
430
combination with cisplatin/vinorelbine. 12 The continuation
of a biologic agent, such as bevacizumab or cetuximab, can
be an option after four to six chemotherapy courses for
responding patients or stable disease. At present, the abovementioned
biological agents are not provided routinely as
part of the standard treatment of patients with NSCLC
through the Brazilian National Health System.
Pemetrexed is an alternative maintenance therapy. Two
recent studies have demonstrated progression-free and overall
survival benefit with the administration of switch maintenance
with pemetrexed (for nonsquamous histology only),
erlotinib, or docetaxel, following four to six courses of
platinum-containing chemotherapy. It should be emphasized,
however, that there is no data to support the continuation
of combination chemotherapy beyond four to six
treatment courses. 28
Systemic Therapy for SCLC
GILBERTO SCHWARTSMANN
SCLC represents approximately 10% to 15% of all lung
cancers. As SCLC has a high risk of early metastatic
dissemination, only a minority of cases (30%) have limited
disease at presentation. Tumor responses to both chemotherapy
and radiotherapy are frequent (50% to 80%), but
relapses are the rule. Platinum plus etoposide chemotherapy
is the cornerstone regimen in the treatment of these
patients. In most centers in Brazil, platinum/etoposide chemotherapy
combined with thoracic radiotherapy is the
choice for patients with limited disease, while chemotherapy
alone is used in patients with extensive disease. Because of
the high risk of central nervous system involvement, prophylactic
cranial irradiation is indicated for complete responders.
Five-year survival of patients presenting with
limited disease varies between 10% and 25%, although it
does not exceed 10% at 2 years in patients with extensive
disease. Most patients relapse within the first two years,
and there are few second-line treatment options for these
patients.
Irinotecan was shown to produce objective responses in
patients with SCLC. In a phase II trial conducted in Japan,
irinotecan was associated with a median survival of 13
months in patients with extensive-stage disease. Subsequently,
a phase III trial comparing cisplatin/irinotecan
with cisplatin/etoposide demonstrated superior median
1-year and 2-year survival rates for the irinotecan arm. 29
This was corroborated by a meta-analysis conducted by
investigators from Sao Paulo, Brazil, that included eight
trials and 3,086 patients with SCLC. 30 Presently, cisplatin/
etoposide, cisplatin/irinotecan, and carboplatin/irinotecan
are the most popular drug regimens used for the treatment
of SCLC in Brazil. Most academic hospital still favor the use
of cisplatin/etoposide with concomitant irradiation as firstline
therapy for patients with limited disease and this
regimen alone for the initial treatment of patients with
extensive disease. The cyclophosphamide/doxorubicin/vincristine
regimen is now rarely used as first-line therapy for
this disease in Brazil.