PATTERN O FUSE OF RADIOTHERAPY FOR LUNG CANCER: A DESCRIPTIVE STUDY. Spanish Study

¿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.

Pemetrexed single agent for "continuation maintenance" therapy in patients with advanced nonsquamous nonsmall-cell lung cancer (NSCLC)

October 28, 2011 — The European Commission has approved pemetrexed (Alimta, Eli Lilly) for use as a single agent for "continuation maintenance" therapy in patients with advanced nonsquamous nonsmall-cell lung cancer (NSCLC), the company announced today. Pemetrexed is the first chemotherapy agent to be approved in Europe for continuation maintenance therapy, according to Eli Lilly. Continuation maintenance therapy refers to the first-line use of a therapy and then its ongoing use in nonprogressors. Other maintenance regimens are currently available for NSCLC, according to a company press statement, but they involve "switch maintenance," in which nonprogressing patients are switched from their first-line treatment to another drug during the maintenance phase. Continuation maintenance therapy is not for every NSCLC patient who responds to first-line treatment, according to a pemetrexed investigator. "Some may have significant toxicity during induction treatment, and it may be worth having a treatment break. [However], a patient who is having a good response in the absence of significant toxicity may be a good candidate for maintenance therapy," said Luis Paz-Ares, MD, PhD, from the Seville University Hospital in Spain, in a press statement at the 2011 annual meeting of the American Society of Clinical Oncology (ASCO). Dr. Paz-Ares was the lead author of the study on which the European approval is based. That phase 3 study, known as PARAMOUNT, is the first large trial to demonstrate that using continuation maintenance therapy can increase progression-free survival in this setting. The study results were first presented at the 2011 ASCO meeting, and were reported by Medscape Medical News at that time. In an earlier study, pemetrexed was found to increase progression-free survival and overall survival, compared with placebo, in this same patient population when used in switch maintenance. In PARAMOUNT, 939 patients were given the standard 4 courses of first-line induction treatment with pemetrexed and cisplatin to induce disease remission. Nonprogressors with a good performance status were then randomized (in a 2:1 ratio) to either maintenance pemetrexed (n = 359) or placebo (n = 180). Median progression-free survival was 4.1 months in the pemetrexed group and 2.8 months in the placebo group. Continuation maintenance therapy with pemetrexed resulted in a significant 38% reduction in the risk for disease progression (hazard ratio, 0.62; P = .00006). Pemetrexed is approved in Europe and the United States for 3 indications in patients with advanced nonsquamous NSCLC — first-line treatment in combination with cisplatin, second-line treatment, and maintenance treatment for patients whose disease does not progress immediately after platinum-based chemotherapy. Maintenance therapy is a controversial treatment strategy in lung cancer and has been discouraged in certain patients by various experts.

High-dose Radiation Improves Lung Cancer Survival, Study Finds

David Muñoz Carmona
Higher doses of radiation combined with chemotherapy improve survival in patients with stage III lung cancer, according to a new study by researchers at the University of Michigan Comprehensive Cancer Center.
Standard treatment for this stage of lung cancer – when the tumor is likely too large to be removed through surgery – involves a combination of radiation therapy with chemotherapy. But, this new study finds, giving chemotherapy at the same time as the radiation enhances the effect of both. Further, increasing the dose of radiation over the course of treatment also increased survival.
“When patients are diagnosed with stage III lung cancer, surgery is often not an option, and survival rates are typically quite low. Finding new ways to improve survival, even in small increments, is crucial,” says senior study author Feng-Ming Kong, M.D., Ph.D., associate professor of radiation oncology at the U-M Medical School and chief of radiation oncology at the VA Ann Arbor Healthcare System.
The study looked at 237 patients who had been treated for stage III non-small cell lung cancer at U-M and the VA Ann Arbor.
The researchers compared survival among patients treated with radiation alone, with radiation followed by chemotherapy, and with radiation and chemotherapy given at the same time. Thirty-one of the patients were also enrolled in a study in which the radiation dose was increased throughout the course of the treatment.
Patients treated with radiation alone had the worst overall survival rates, living only an average 7.4 months after diagnosis. Adding chemotherapy increased survival to 14.9 months when it was administered after completing radiation and 15.8 months when administered at the same time as radiation. After five years, 19.4 percent of the patients receiving concurrent chemotherapy were still alive, compared to only 7.5 percent of patients receiving sequential chemotherapy.
“Our study shows chemotherapy helps, and high dose radiation helps. But it’s challenging to administer these treatments at the same time because of the potential toxicity associated with the high dose radiation,” Kong says.
U-M researchers are currently looking at using PET imaging during the course of lung cancer treatment to personalize high dose radiation therapy in many individual patients. As the tumor becomes smaller during treatment, increasing the radiation dose will become more tolerable because it is targeting a smaller area. The U-M researchers believe this strategy could lead to improved treatment outcomes in many patients. Kong currently leads a clinical trial that is following patients through their treatment to look at the impact on survival of increasing radiation dose.
Lung cancer statistics: 215,000 Americans will be diagnosed with lung cancer this year and 161,800 will die from the disease, according to the American Cancer Society
Additional authors: Li Wang, M.D., Ph.D.; Candace R. Correa, M.D.; Lujun Zhao, M.D., Ph.D.; James Hayman, M.D.; Gregory P. Kalemkerian, M.D.; Susan Lyons, M.D., Ph.D.; Kemp Cease, M.D.; and Dean Brenner, M.D.
Funding was provided through the Pardee Foundation and an American Society of Clinical Oncology Career Development Award.
Reference: International Journal of Radiation Oncology*Biology*Physics, Vol. 73, No. 5, pp. 1383-1390