Combination of high-dose radiotherapy and chemotherapy shows encouraging results in treating LSCL

University of Texas M. D. Anderson Cancer CenterNov 4 2009

Treating limited stage small cell lung cancer(LSCL) with a combination of accelerated high-dose radiotherapy and chemotherapy has shown encouraging results, opening the door to larger scale investigation, according to new research from The University of Texas M. D. Anderson Cancer Center.

The Phase II study was presented today (Nov. 3) in an oral session at the annual meeting of the American Society for Radiation Oncology (ASTRO), by Ritsuko Komaki, M.D., professor and program director of Lung Cancer Research and Thoracic Radiation Oncology, Department of Radiation Oncology at M. D. Anderson.

"While still early, these may be the most important study findings for limited stage small cell lung cancer in the past decade," said Komaki, the study's lead author. "This research is important because it achieved a high level of control of the disease while minimizing damage to the esophagus."

According to the American Cancer Society, lung cancer is the leading cause of cancer death for men and women in this country. Almost 220,000 cases will be diagnosed in 2009, and more than 159,000 people will die of the disease.

Small cell lung cancer is an aggressive cancer that accounts for about 20 percent of lung cancers; approximately 20 percent of these cases are classified as LSCL, defined as cancer present in one lung and possible lymph node involvement, but has not metastasized.

"Over the past few years, we have made significant progress by giving concurrent chemotherapy and thoracic radiotherapy (radiation to the chest), as well as prophylactic cranial radiotherapy (radiation to the head to prevent cancer)," said Komaki, who also holds the Gloria Lupton Tennison Distinguished Professorship in Lung Cancer Research at M. D. Anderson. "However, five-year survival in limited stage small cell lung cancer is still only 26 percent, and the likelihood of recurrence and metastasis is still too high."

A previous phase III study conducted at M. D. Anderson and other sites through the North America Intergroup, showed accelerated fractionated radiotherapy (treatment in which radiation levels are increased over time) with concurrent VP-16 (etoposide) and cisplatin (platinum-based drugs) improved five-year survival rates. But this treatment often causes other side effects.

"Severe inflammation of the lining of the esophagus, also known as acute esophagitis, is a significant risk in this type of treatment," Komaki said. "Therefore, despite its long-term survival benefit, this modality has not been popular in community hospitals."

Researchers at M. D. Anderson and their colleagues developed this new study to find a way to increase the level of radiation during concurrent chemotherapy without increasing damage to normal tissue. Supported by NCI grant, this clinical study was then proposed to the Radiation Therapy Oncology Group (RTOG).

Patients with LSCL were treated with thoracic radiotherapy that was accelerated slowly over three weeks. The next step included two weeks of higher radiation levels twice daily, for a total of five weeks. During radiotherapy, patients received four cycles of chemotherapy.

"We gave the patients boosts of radiation twice a day in the last two weeks of treatment, when resistant cells often start to proliferate," Komaki said.

During the median follow-up time of 19 months, 41 percent of patients experienced complete response, and another 39 percent had partial response. Despite the higher radiation dose, the rate of acute severe esophagitis was significantly lower than the previous study, 18 percent, vs. 27 percent, respectively.

However, at 36.6 percent, the two-year survival rate did not improve. In addition, while local control of the disease was excellent, 80 percent, the majority of patients still developed distant metastasis, Komaki said.

Komaki said further study is needed, possibly including a cycle of induction chemotherapy before concurrent treatment. Improved systemic treatment and staging work-ups are needed too, she said.

This study has been adapted by a new randomized intergroup trial (CALGB/RTOG/ECOG/SWOG) that will enroll 700 patients in multiple sites across the country. This research will compare three radiation dose levels and treatment duration times.