¿Más es Mejor en Cáncer de Pulmón?

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.