CHICAGOAlthough concomitant platinum-based systemic
chemotherapy and thoracic radiotherapy have yielded the best short-term
survival rates for patients with limited-stage small-cell lung cancer (SCLC),
this approach produces few long-term survivors because local failure and
distant metastasis are common.
That is why Charles R. Thomas, Jr, MD, suggested that
oncologists encourage patients who reach the 2-year mark after current
treatment to participate in chemoprevention studies involving novel
antiproliferative systemic agents directed at inhibiting tumor growth and
retarding disease progression. Dr. Thomas is a radiation and medical oncologist
at the University of Texas Health Science Center at San Antonio/San Antonio
Cancer Institute and a member of the Southwest Oncology Group (SWOG).
Long-Term Results of SWOG 8269
In a presentation at the annual meeting of the Radiological
Society of North America (RSNA), Dr. Thomas reported the long-term results from
SWOG 8269, the first North American cooperative experience with concomitant
cisplatin (Platinol), etoposide (VePesid), and external beam radiation therapy
for limited-stage SCLC. Preliminary results of the trial had been published
previously after a follow-up period of 3 years, and a further analysis of data
concerning patterns of failure was performed after a median follow-up period of
Because of recent observations in the literature about
long-term survival of patients with limited-stage small-cell lung cancer, SWOG
again reviewed data after a minimum follow-up interval of 13.1 years, maximum
interval of 14.5 years, and median interval of 13.4 years, and Dr. Thomas
reported on these findings.
When SWOG 8269 began, it enrolled 123 patients between April
1985 and May 1986. After excluding nine patients, the trial evaluated 114
patients from 47 institutions who received induction chemotherapy,
consolidative chemotherapy, and thoracic irradiation.
Induction therapy consisted of three cycles of IV cisplatin 50
mg/m2 on days 1 and 8, 29 and 36, and 57 and 64; IV etoposide 50
mg/m2 on days
1 through 5, 29 through 33, and 57 through 61; and IV vincristine 1.4 mg/m2 on
days 15, 22, 43, and 50. Consolidative chemotherapy involved two cycles of
vincristine, methotrexate, etoposide, doxorubicin, and cyclophosphamide
A total thoracic irradiation dose of 45 Gy was administered
concomitantly in 25 daily fractions at 1.8 Gy per fraction. A total cranial
irradiation dose of 30 Gy was administered in 15 fractions at 2.0 Gy per
fraction with the third cycle of chemotherapy.
As of May 2000, 5 of the 114 patients (4%) were alive and free
from disease progression. The median progression-free survival was 12 months,
and overall survival was 19.5 months. After 2 years, approximately one third of
patients were progression free, but by 5 years, only one fourth of patients had
no signs of disease progression. Two fifths of patients were alive at the end
of 2 years, but only one fourth were alive at the end of 5 years.
Second Primary Cancers
A significant subset of patients developed second primary
cancers. Second primary cancers were responsible for the deaths of 29% of 38
patients who died of causes other than small-cell lung cancer.
Second primary cancer tumor types included acute myelogenous
leukemia (AML), squamous cell lung cancer, breast cancer, prostate cancer,
pancreatic cancer, renal cell carcinoma, and myelodysplasia. One patient had
both melanoma and non-Hodgkin’s lymphoma.
A pattern-of-failure analysis involving 76 patients who died of
SCLC revealed that local recurrence was a factor in nearly half. Exclusively
local failure occurred in one quarter of patients; distant metastasis was the
first sign of treatment failure in more than one third of patients; both local
and distant failure occurred in approximately one quarter.
Late failures were detected up to 13 years after treatment.
Both progression-free and overall survival curves continued to flatten after 12
years, indicating that the risk for late failure or a second malignancy follows
survivors well into the second decade after therapy, he said.
Data from SWOG 8269 appear to suggest that progression of SCLC
accounts for most of the failures and deaths during the first 3 years after
treatment. The cause of treatment failure in subsequent years is not as clear
because of confounding variables, such as continued use of tobacco products and
upper airway or digestive tract malignancies, he said.
Dr. Thomas indicated that because the survival and disease-free
progression curves continue to decline with long-term follow-up, "it would
make sense to develop clinical trials to study the effect of maintenance or
prophylactic novel anti-proliferative systemic agents because classic cytotoxic
chemotherapy and concomitant radiation therapy alone is not going to be the