Hanna's work challenges consolidation approach in clinical practice for stage III lung cancer
The addition of docetaxel to both concurrent chest radiation and a regimen of two chemotherapy drugs, cisplatin and etoposide, does not significantly improve survival for patients with inoperable stage III non-small cell lung cancer (NSCLC) and does add significant toxicity. These new findings from a phase III trial were presented by Nasser Hanna, MD, of Indiana University Melvin and Bren Simon Cancer Center, at the American Society of Clinical Oncology 2007 Annual Conference.
Published results in 2003 from a single-arm, phase II Southwest Oncology Group (SWOG) study reported that docetaxel following concurrent chemotherapy and radiation improved median survival time to 26 months for these stage III NSCLC patients. Since then, about 70 percent of physicians have adopted this regimen without confirmation from a randomized trial.
Hanna’s randomized, prospective phase III Hoosier Oncology Group (HOG) study sought to test whether docetaxel is in fact responsible for these favorable results. Of the 243 patients enrolled in the study, one-half were observed with concurrent chemotherapy and radiation therapy and one-half received the additional docetaxel. For inclusion in the study, patients had to have unresectable, phase III NSCLC and pass a lung function test.
Survival was similar on both arms of the trial, indicating that the addition of docetaxel did not improve survival. However, high side effects and risk were more likely to occur in those patients who received the docetaxel - including increased infections, pneumonitis, hospitalization and deaths. Due to the toxicities reported, the study was stopped early at the recommendation of the Data Safety Monitoring Board after an analysis based upon the first 203 patients entered and 147 randomized patients.
“Significant advances are unlikely to come from continued exploration of consolidation chemotherapy,” Hanna said. “It's a difficult treatment to give, and you're not going to see a big difference. This is not going to lead us in that direction, and I believe we need to re-think this.”
Mark Green, MD, of the Network for Medical Communication and Research Analysis Group, agreed with this assessment in his discussion of this study.
“Dr. Hanna brilliantly analyzed his own data,” he said. “This sequential chemotherapy approach has frequently been positive.” He noted that the study, to be highlighted in the upcoming Best of ASCO Regional Sessions, has the potential to change practice once its results are better understood and digested by oncologists.
A HOG phase II trial that is currently open and accruing patients is now looking at improving outcomes for this patient population by combining the antiangiogenic drug sarafenib with concurrent chemotherapy and radiation. Antiangiogenic drugs that inhibit the growth of blood vessels that supply nutrients to the tumor have already been shown to be effective in renal, breast and colon cancer, and to some extent, metastatic non-small cell lung cancer.
“We are the first to do an antiangiogenic study in stage III, unresectable lung cancer, and we are breaking new ground,” says Hanna.
ASCO Daily News Coverage Monday, June 4, 2007
Consolidation with Docetaxel in NSCLC After Concurrent Chemoradiotherapy
Abstract from ASCO 2007 Annual Meeting
Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 7512
Other sub-analyses of study presented at ASCO 2007 Annual Meeting
F.O. Ademuyiwa, et. al., Multivariate analysis of prognostic variables associated with survival from a phase III study of cisplatin (P) plus etoposide (E) plus chest radiation (XRT) with or without consolidation docetaxel (D) in patients with unresectable stage III non-small cell lung cancer (NSCLC).
M.M. Sgroi, et. al. An analysis of elderly patients (pts) treated on a phase III trial of cisplatin (P) plus etoposide (E) with concurrent radiotherapy (CRT) followed by docetaxel (D) vs observation (O) in pts with stage III non small cell lung cancer (NSCLC).