Dr. van Hazel also described the results reported at ASCO as "fantastic" and told ONI that the danger, if any, of long-term radiation toxicity was relative to the success of treatment with SIR-Spheres. The disease being treated currently has a time to progression of about 8 months after chemotherapy and a median survival of 16 to 20 months, according to Dr. van Hazel. "We’re nowhere close to our median survival," he said, noting that, as of May 2002, the time to progression with SIR-Spheres was double the expectation. "So if we run into radiation toxicity, it will be because of this prolonged survival," he said.
All 21 patients in the trial received the then-standard chemotherapy regimen of 425 mg/m2 of fluorouracil(Drug information on fluorouracil) and 20 mg/m2 of leucovorin for 5 days. This was repeated every 28 days until progression. Eleven patients also were implanted with SIR-Spheres during the second cycle of chemotherapy.
Although the patients who received SIR-Spheres had more than double the number of grade 3-4 adverse events (13 vs 6), the investigators said the toxicity was acceptable and that quality of life was similar for both cohorts of patients. Dr. van Hazel described the toxicity as normal for patients undergoing chemotherapy for liver metastases.
The trial was halted in 1999 after Leonard Saltz, MD, of Memorial Sloan-Kettering Cancer Center, reported that adding irinotecan(Drug information on irinotecan) (Camptosar) to the standard treatment significantly increased response rates in these patients.
Drs. Gray and van Hazel said they felt they could not subsequently recruit patients to a phase III trial giving only the standard fluorouracil/leucovorin treatment. Instead, they told ONI that they are opening new phase II arms in which patients will be given a chemotherapy regimen containing irinotecan or oxali-platin (Eloxatin) and possibly another regimen as well.