But while the 13-year study showed a clear benefit with combining radioisotopes, the approach is unlikely to become the standard of care anytime soon, senior author Dr. Martin Walter of the Institute of Nuclear Medicine at the University Hospital of Bern told Reuters Health.
"Right now," he wrote in an email, "the vast majority of centers still use the single isotope approach. It is unlikely that an established standard of care anywhere in the world will be changed based on a single center experience -- and it should not."
More studies would be needed to confirm the findings, but those studies are not likely to happen, Dr. Walter said.
He said radiopeptide therapy, known as DOTATOC, was developed by a university. Swiss physicians have 16 years of successful clinical experience using it, but there is little funding available for larger, prospective trials.
"In contrast to nearly all other anticancer drugs, DOTATOC was not developed by a pharmaceutical company, but by a university hospital department," Dr. Walter said. "Every company that has established their drug on the market would potentially harm their sales by testing their drug against DOTATOC -- which is understandable to some degree. However, the lack of corporate funding led to a lack of randomized evidence for DOTATOC."
Current standard practice for radiopeptide therapy is to bind a single radioisotope like yttrium-90 (Y-90) or lutetium-177 (Lu-177) to a synthetic peptide like octreotide. Both are beta emitters, however Y-90 is a high-energy, long-range emitter, whereas Lu-177 is a short-range, low-energy emitter. Dr. Walter and his colleagues sought to capitalize on the complementary characteristics of the two radioisotopes by combining them to target both large and small neuroendocrine tumor metastases.
In a paper online March 5 in the Journal of Clinical Oncology, the investigators compared 237 patients who received Y-90 DOTATOC with 249 patients who received alternating doses of Y-90 DOTATOC and Lu-177 DOTATOC. Everyone completed at least three cycles of somatostatin-based treatment.
With similar follow-up in both groups (roughly 34 months), the median survival was significantly longer with the Y-90 and Lu-177 combination compared with Y-90 alone: 66.1 versus 47.5 months (p = 0.006; HR, 0.64).
This difference was accomplished without any spike in adverse event rates. The incidence of side effects was similar for the two groups, even for severe renal toxicity (8.9% versus 11.2%; p = 0.47), the main adverse event associated with radiopeptide therapy for neuroendocrine cancers.
Dr. Walter noted that in a cohort study such as this one, "unknown prognostic factors might [have been] unbalanced between the two treatment groups" and any differences could have affected the overall outcome of the study.
Also, he said, patients were enrolled over the course of 13 years and strategies for both medical treatment and supportive care changed over that period, possibly influencing patient outcomes.
Still, he said, "Physicians that have used DOTATOC or that have referred patients to DOTATOC know about the beneficial effects."
The current study included patients referred from more than 80 centers in 19 countries. Dr. Walter said that since 1997, when the treatment was first offered, "hundreds of American patients" have traveled to Switzerland for DOTATOC.
By Gabriel Miller
J Clin Oncol 2012.
Last Updated: 2012-03-14 14:55:13 -0400 (Reuters Health)
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