Radioembolization plus Fluorouracil Active in Colorectal Cancer Patients with Liver Metastases

Radioembolization plus the chemotherapy agent fluorouracil slows cancer progression for colorectal cancer patients whose disease has progressed following prior treatment with chemotherapy and have metastases limited to the liver. These findings were recently published in the Journal of Clinical Oncology.[1]

Colorectal cancer is the second leading cause of cancer-related deaths in the United States. The primary cause of death related to colorectal cancer is cancer spread to the liver, referred to as liver metastasis. The surgical removal of liver metastasis appears to provide optimal outcomes for patients with this stage of disease. However, patients are often not able to have this type of surgery. Reasons a patient may not be eligible for surgical removal of liver metastasis include: the extent of cancer spread within the liver; the size of cancerous tumors within the liver; placement of the cancer within the liver; a patient’s overall health.

Patients with inoperable liver metastasis may be treated with chemotherapy, radiofrequency ablation (a procedure in which radio waves are directed into the tumor(s) with a probe), or radiation therapy. With a goal of improving the duration of survival for these patients, researchers continue to evaluate novel ways to treat inoperable liver metastasis.

Radioembolization is another strategy to optimize the delivery of radiation to liver metastases while sparing healthy tissue. This strategy utilizes radioactive microspheres (small spheres containing radioactive material). The small spheres are injected into vasculature of the liver, where they tend to get lodged in the vasculature responsible for providing blood and nourishment to the cancer cells. While lodged in place, the radioactive substance spontaneously emits radiation to the surrounding cancerous area while minimizing radiation exposure to the healthy portions of the liver. Results from a small study published in the Journal of Clinical Oncology indicated that radioembolization with concomitant chemotherapy (oxaliplatin, fluorouracil, and leucovorin) was active in colorectal cancer patients with inoperable liver metastases who had no prior treatment; median time to cancer progression within the liver in this study was over one year.

The current study—a large prospective, multicenter, randomized Phase III trial—was designed to evaluate the safety and efficacy of radioembolization combined with the chemotherapy agent fluorouracil in heavily pretreated colorectal cancer patients. All 44 patients in this study had metastatic colorectal cancer with inoperable metastases limited to the liver and had disease progression following standard chemotherapy including the agents fluorouracil, oxaliplatin, and irinotecan. Patients were randomized to receive either treatment with fluorouracil alone or radioembolization plus fluorouracil. At a median follow-up of 24.8 months, radioembolization plus fluorouracil significantly improved the median time to tumor progression and the time to liver progression (see Table 1). In addition, treatment with the radioembolization plus fluorouracil was well tolerated with only one patient experiencing significant toxicity compared with six patients in the fluorouracil arm.

Table 1: Time to liver progression, time to tumor progression, and median overall survival for patients receiving fluorouracil alone compared with radioembolization plus fluorouracil.

Fluorouracil Alone (n= 23) Radioembolization plus fluorouracil (n=21) P value
Median time to liver progression (months) 2.1 5.5 .003
Median time to tumor progression (months) 2.1 4.5 .03
Median overall survival (months) 7.3 10.0 .80

The researchers concluded that radioembolization combined with fluorouracil may benefit metastatic colorectal cancer patients with liver-limited disease who have progressed following prior chemotherapy.

Reference:


[1] Hendlisz A, Van den Eynde M, Peeters M, et al. Phase III Trial Comparing Protracted Intravenous Fluorouracil Infusion Alone or With Yttrium-90 Resin Microspheres Radioembolization for Liver-Limited Metastatic Colorectal Cancer Refractory to Standard Chemotherapy. Journal of Clinical Oncology [early online publication]. June, 21 2010.

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