SIRT Slows Growth of Colorectal Cancer Liver Metastases

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Oncology NEWS InternationalOncology NEWS International Vol 11 No 10
Volume 11
Issue 10

ORLANDO-Delivering Selective Internal Radiation Therapy (SIRT) via radioactive microspheres (SIR-Spheres) significantly increased response to treatment and time to progression in a small cohort of patients receiving chemotherapy for advanced colorectal cancer liver metastases.

ORLANDO—Delivering Selective Internal Radiation Therapy (SIRT) via radioactive microspheres (SIR-Spheres) significantly increased response to treatment and time to progression in a small cohort of patients receiving chemotherapy for advanced colorectal cancer liver metastases.

Ten of 11 patients responded to the combination of yttrium-90 microspheres and chemotherapy, according to phase II trial results reported at the 38th Annual Meeting of the American Society of Clinical Oncology (abstract 599). Their median time to progression was 15.6 months—10.9 months longer than recorded for a control group of 10 patients who received only chemotherapy. None of the control patients responded to the chemotherapy regimen alone.

Bruce Gray, MBBS, MS, PhD, developer of SIR-Spheres and medical director of SIRTeX Medical Ltd., New South Wales, Australia, presented the data with investigator Guy van Hazel, MBBS, FRCP, FRACP, of Perth Oncology, Mount Hospital, Perth, Australia.

Characterizing the response rate as "extraordinarily high," Dr. Gray pointed to 11 sets of before-and-after CT scans (see Figure 1  and Figure 2) and told ONI: "If you don’t believe the data, you don’t have to, because the pictures are there and you can see it."

The US Food and Drug Administration (FDA) announced in March its approval of SIR-Spheres, based on a previous randomized trial, for use in the treatment of unresectable metastatic liver tumors from primary colorectal cancer in combination with intrahepatic artery chemotherapy with floxuridine. SIR-Spheres has since been used on its first US patient in Phoenix, Arizona, Dr. Gray said, and at a number of other US institutions. (For more information on US centers using SIR-Spheres, see www.sirtex.com.)

About 32 microns in diameter, the radioactive microspheres (Figure 3) are delivered into the hepatic artery via a catheter in the groin and locate permanently in the liver. Because liver tumors receive the vast majority of their blood supply from the hepatic artery, the microspheres tend to concentrate in the tumor, which may receive as much as five to six times the amount of radiation delivered to normal liver tissue, which receives most of its blood supply from the portal vein.

The procedure can be done on an outpatient or inpatient basis with an overnight stay in the hospital. "Then they go home, and they’re selectively irradiated over the next 2 weeks while going about their normal activities," Dr. Gray said. After 2 weeks, only 2.5% of the original radioactivity remains.

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 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 (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. 

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