Standard-Dose Radiation Bests High-Dose Radiation in Advanced NSCLC
IMNG Medical Media, 2013 May
16, P Wendling
Standard-dose radiation
produced better overall survival and locoregional control than did high-dose
radiation when given with concurrent chemotherapy in patients with newly
diagnosed stage III non–small cell lung cancer in the phase III, randomized
RTOG 0617 trial.
Patients
on the high dose had a 56% greater risk of death than those on a standard 60 Gy
dose. Median overall survival times were 18.5 months with high-dose radiation
and 28.7 months with a standard dose (hazard ratio, 1.56;P = .0007).
The
risk of local failure also was increased by 37% in the high-dose arm (HR, 1.37; P = .03).
“At
this point, there is no clear reason for the poor outcome we experienced on the
high-dose arm,” lead author Dr. Jeffrey Bradley said in a press briefing
highlighting studies to be presented at the upcoming annual meeting of the American Society of Clinical
Oncology (ASCO).
The
most likely culprit is unreported toxicities, although other possible
explanations are increased heart dose, longer duration of therapy, or a
combination of these factors, he said.
The
results are surprising because conventional thinking has been that higher doses
of radiation would more effectively kill the tumor and thereby improve
survival.
A
phase-III trial in the 1970s established the standard radiation dose of 60 Gy
in this setting but, over time, several radiation dose-ranging phase-II studies
have reported promising results and improved median survival times with
radiation doses up to 74 Gy, explained Dr. Bradley, professor of radiation
oncology and chief of the thoracic service at Washington University, St. Louis.
At
the same time, improvements in technology such as three-dimensional radiation
therapy (RT) and intensity-modulated RT techniques have made RT delivery more
precise, allowing organs and tissues sensitive to radiation to receive less
radiation while the tumor receives more. This technique was explored in
Radiation Therapy Oncology Group (RTOG) 0617.
“This
is a very surprising result, especially when using these special radiation
techniques that were designed to be more precise, you would expect that the
outcome would be better,” ASCO president Sandra Swain, medical director of the
Washington (D.C.) Cancer Institute, told reporters. “This should really put an
end to higher-dose treatments, given the better outcomes in the standard-dose
arms.”
Dr.
Bradley said, “A lot of phase-III trials turn out negative when phase-II trials
look good, so I think it was good to do a phase-III trial and get this
answered.”
RTOG
0617 randomly assigned 464 patients with newly diagnosed, unresected stage-III
non–small cell lung cancer to conformal RT to 60 Gy, five times per week for 6
weeks or to 74 Gy five times per week for 7.5 weeks. All patients received
concurrent chemotherapy with weekly paclitaxel (Taxol) and carboplatin, with a
second randomization for patients to receive consolidation chemotherapy with or
without cetuximab (Erbitux).
Among
the 419 patients available for analysis at 18 months, local failure rates were
25% with standard-dose RT and 34.3% with high-dose RT (P = .03, as noted above), Dr. Bradley
reported.
Median
18-month overall survival rates were 67% with the standard radiation dose vs.
54% with the high dose.
Median
overall survival times in both groups were higher than expected, but “the
overall survival benefit of 60 Gy is independent of the cetuximab question,” he
said. Data from that portion of the trial are expected to be reported in 2014.
Finally,
the only significant difference in physician-reported side effects was a
slightly higher rate of esophagitis in the high-dose arms (21% vs. 7%).
Full
details of RTOG 0617 (abstract 7501) will be reported 10:15 a.m. on June 4 at
ASCO’s annual meeting in Chicago.
The
study was supported by the National Cancer Institute. Dr. Bradley reported
having no relevant financial disclosures. A coauthor reported research funding
from the NCI.
