Somnath Mukherjee, MD
Capecitabine produces similar local disease control with lower toxicity versus gemcitabine when combined with radiotherapy following induction chemotherapy in patients with locally advanced pancreatic cancer.
The phase II randomized SCALOP trial showed a median progression-free survival of 12 months in patients assigned to capecitabine/radiotherapy compared with 10.4 months in those randomized to gemcitabine/radiotherapy, a difference that was not statistically significant (hazard ratio = 0.60; P
= .111). Overall survival, a secondary endpoint, favored capecitabine/radiotherapy, however.
The findings were presented by Somnath Mukherjee, MD, at the 2013 Gastrointestinal Cancers Symposium.
The optimal treatment of locally advanced pancreatic cancer is unresolved, as few randomized controlled trials have been conducted in this setting. “There is a bit of debate as to what is the standard of care. An ongoing trial from France—LAP 07—is comparing chemotherapy and chemoradiation and the results will probably be available later this year,” said Mukherjee. “At the moment, both are considered standards of care.”
Survival of about 10 months has been reported with the use of chemotherapy alone and chemoradiation. Selection of treatment after disease control with chemotherapy varies by region. In the United Kingdom, the current standard has been chemotherapy alone, Mukherjee said, whereas in the United States, the use of chemotherapy combined with radiotherapy is more common.
The SCALOP study sought to test the feasibility and activity of chemotherapy (capecitabine or gemcitabine) combined with radiotherapy following induction chemotherapy with three cycles of the combination of gemcitabine and capecitabine (GemCap). The feasibility of delivering chemoradiation in a multicenter setting in the United Kingdom has been unknown, said Mukherjee, senior clinical researcher, Oxford University.
After induction therapy, 74 patients with stable disease were randomized to an additional GemCap cycle followed by either gemcitabine with radiation or capecitabine with radiation. The median radiation dose in each group was 50.4 Gy.
Both treatment arms passed the Fleming’s design parameters, which allows for stopping treatment if one therapy is ineffective. Median progression-free survival at 9 months, the primary endpoint, was not significantly different between the groups (62.9% in the capecitabine/radiotherapy arm vs 51.4% in the gemcitabine/radiotherapy arm).
“There was a suggestion that survival might actually be better with capecitabine than with gemcitabine,” Mukherjee said. Median overall survival was almost 2 months longer in the capecitabine/radiotherapy arm versus the gemcitabine/radiotherapy arm (15.2 months vs 13.4 months; P
No patients in the capecitabine/radiotherapy arm suffered grade 3 or 4 hematologic toxicity, compared with 18.4% in the gemcitabine/radiotherapy arm (P
= .007). The rates of grade 3/4 nonhematologic toxicity were 11.1% in the capecitabine/radiotherapy arm versus 26.3% in the gemcitabine/radiotherapy arm (P
“If LAP 07 comes back showing that capecitabine/radiotherapy is better than chemotherapy on its own, I do not think anybody will go back to doing a study of gemcitabine/radiotherapy and capecitabine/radiotherapy,” said Mukherjee. “It will definitely help in defining the standard of care or at least give us the direction we should be traveling.”
Somnath Mukherjee S, Chris Hurt C, Gareth Griffiths G, et al. SCALOP: Results of a randomized phase II study of induction chemotherapy followed by gemcitabine (G) or capecitabine (Cap) based chemoradiation (CRT) in locally advanced pancreatic cancer (LANPC). J Clin Oncol 30: 2012 (suppl 34; abstr LBA146).