CHICAGO, June 4 -- For locally advanced unresectable pancreatic cancer, chemoradiation may add a few weeks of survival compared with chemotherapy alone, according to a small randomized trial.
Radiotherapy plus gemcitabine (Gemzar) improved survival from 9.2 to 11.0 months (P=0.034) without a benefit for progression-free survival, reported Patrick J. Loehrer, Sr., M.D., of Indiana University in Indianapolis, and colleagues at the American Society of Clinical Oncology meeting here.
Action Points
- Explain to interested patients that the use of radiation therapy for patients with locally advanced, unresectable pancreatic tumors is controversial.
- Note that this study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
For every day of radiation, patients survived an additional 1.9 days, commented Robert A. Wolff, M.D., of the M.D. Anderson Cancer Center in Houston, who was a discussant on the study.
The findings "suggest radiation has a role in the treatment of patients with locally advanced disease," he said, but the regimen would "need further refinement before it could be broadly applied" because of higher toxicity.
The E4201 study randomized patients to gemcitabine induction and consolidation at a dose of 1,000 mg/m2 per week alone or at a dose of 600 mg/m2 during induction with concurrent three-dimensional conformal radiotherapy at 180 cGy per day for a total of 50.40 Gy followed by gemcitabine consolidation.
Enrollment ended early because of poor accrual with a total of 74 loco-regionally advanced pancreatic cancer patients who had good performance status.
One reason for the poor accrual was that some oncologists thought it was unethical to use radiation while others thought it was unethical not to use radiation, Dr. Loehrer said. "It remains a sobering reality that in nearly three decades of research, the true impact of radiation therapy in pancreatic cancer is still controversial."
Because of the small size of the trial -- only 25% of planned enrollment -- "I would really call it a randomized phase II," Dr. Wolff said.
During follow-up, all participants died. Median overall survival, the primary endpoint, was significantly longer with radiochemotherapy than with chemotherapy alone (HR 0.574, P=0.034).
Progression-free survival, though, showed no advantage for the combination of gemcitabine and radiation (6.0 versus 6.7 months, HR 0.821, P=0.50).
The researchers noted that surrogate markers of progression, such as pain and anorexia, are commonly used in these patients making measuring objective response difficult.
For the chemoradiation, the response rates compared with chemotherapy alone included:
- Partial response in 6% versus 5% of patients.
- Stable disease in 68% versus 35% of patients.
- Progression in 6% versus 16% of patients.
- Clinical progression without confirmation scans in 21% versus 46%.
Early overall survival rates were similar between groups but separated over time (29% versus 11% at 18 months and 12% versus 4% at 24 months), which Dr. Wolff said shows that radiation benefits only patients with more favorable tumor biology.
In locally advanced disease, chemotherapy can identify patients with poor tumor biology and spare them radiation, which is unlikely to be effective.
Three studies including one from his center have shown improved survival with chemotherapy first and then giving radiation only to those who do not progress, Dr. Wolff said. "So I think we now have an emerging strategy for locally advanced pancreatic cancer."
Patients should have induction chemotherapy then be restaged so that those with localized disease can have radiochemotherapy followed by observation while those with metastatic disease are given second line therapy or best supportive care, he said.
Toxicity was "formidable" with grade 3-4 events in 93% of patients who had radiotherapy and 82% of those who did not. Chemoradiation was associated with more gastrointestinal grade 3-4 events (38% versus 14%, P=0.03) and more grade 3-4 fatigue (32% versus 6%, P=0.006).
| Dr. Loehrer reported conflicts of interest in the form of research funding from Eli Lilly, Novartis, AstraZeneca, and Imclone. Dr. Wolff reported conflicts of interest for Eli Lilly, Genentech, and sanofi-aventis. |
Primary Source
American Society of Clinical Oncology
Source Reference: Loehrer PJ, et al "A randomized phase III study of gemcitabine in combination with radiation therapy versus gemcitabine alone in patients with localized, unresectable pancreatic cancer: E4201" ASCO Meeting 2008; Abstract 4506.