High-dose radiation improves lung cancer survival, U-M study finds

Concurrent chemotherapy, radiation also linked to better survival

ANN ARBOR, Mich., 09 april 2009 — 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 Ann Arbor VA Healthcare System.

The study, published in the April 1 issue of the International Journal of Radiation Oncology*Biology*Physics, 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.

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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: Pardee Foundation, American Society of Clinical Oncology Career Development Award

Two drugs don't boost lung cancer survival: Roche

By Emma Thomasson and Ben Hirschler
07 oct 2008--Roche Holding AG and Genentech Inc said on Monday a study into the benefits of combining their Tarceva and Avastin drugs for lung cancer patients did not show an increase in overall survival.
Both drugs are targeted therapies -- modern medicines which act as "smart bombs" by crippling cancer cells while leaving healthy cells intact. It had been hoped that adding them together would extend patients' lives.
Roche and Genentech said on Monday a Phase III study investigated the addition of Avastin to Tarceva compared with Tarceva alone for the treatment of patients with advanced non-small cell lung cancer, the most common form of lung cancer.
The study did not show a significant increase in overall survival with the Avastin-Tarceva combination compared with Tarceva alone.
But there was evidence of an increase in the time patients lived without their disease getting worse as well as the response rate when Avastin was added to Tarceva compared with Tarceva alone.
Deutsche Bank analysts said the result was "somewhat disappointing" as combining the two drugs was an attractive treatment option, with the potential to increase efficacy without undue side effects.
But the high cost -- around $12,000 a month -- meant using both drugs would only be considered if there was convincing clinical data.
Roche said further analysis was needed and the full results of the study would be submitted for presentation at a conference on thoracic oncology in Chicago next month.
Both Avastin and Tarceva are already available for the treatment of patients with advanced lung cancer in the United States and Europe.
"We are disappointed this study did not show an improvement in survival for patients with advanced lung cancer who have a poor prognosis and a disease that is extremely difficult to treat," said Genentech chief medical officer Hal Barron.
"We are, however, encouraged to see the combination of Avastin and Tarceva had clear evidence of biological activity, and will fully analyze the data so that we can apply the insights to our ongoing lung cancer research."
Panmure analysts said the result was a boost for AstraZeneca Plc, whose drug Zactima is in Phase III clinical trials in lung cancer. A strong result for the Tarceva/Avastin combination could have undermined the market for Zactima.
Roche, the world's largest maker of cancer drugs, wants to buy Genentech, which is already majority-owned by Roche. Genentech rejected a $89 per share bid from Roche in mid-August -- valuing the remainder of Genentech at $43.7 billion -- but Roche has said it is committed to its takeover proposal.

Brain radiation increases lung cancer survival

Preventive radiation to the brain significantly reduces the risk of lung cancer spreading to this organ and improves survival, according to data presented in a session Monday at the 43rd annual meeting of the American Society of Clinical Oncology.
All of the patients studied had advanced small-cell lung cancer, a type that carries a poor prognosis and is generally not amenable to surgical removal.
"Brain metastases are a common problem in small-cell lung cancer," study coordinator Dr. Ben Slotman, professor and chairman of radiation oncology at VU University Medical Center, Amsterdam, noted at a press briefing.
Previous studies have shown that brain radiation to prevent the cancer from invading this organ can extend survival in patients with limited small-cell lung cancer. The current study suggests that "all patients with small-cell lung cancer who respond to chemotherapy could benefit from" brain radiation, Slotman said.
In the study, 286 patients with advanced small-cell lung cancer and any response to chemotherapy were randomly assigned to preventative brain radiation or no radiation.
Preventative radiation was well tolerated; side effects were generally mild and consisted largely of headache, nausea/vomiting and fatigue, Slotman reported. Moreover, this treatment "did not adversely affect quality of life," he said.
Results showed that brain radiation significantly reduced the risk cancer spreading to the brain. After 1 year, there was brain involvement in 14.6 percent in the radiation group versus 40.4 percent in the comparison group.
Moreover, brain irradiation improved survival. At 1-year, the survival rate was 27.1 percent in the group that received preventative radiation compared to only 13.3 percent in the group that did not.
"Because improvements in treatment results for patients with advanced small-cell lung cancer have been minimal in the past two decades, these findings represent a significant advance," Slotman noted in a written statement.
Based on these findings, preventative radiation of the cranium should be "routinely be offered to all responding patients with (advanced) small-cell lung cancer," he told conference members.