Michael P Thirlwell | PubMed Health

PubMed2002

Randomized, open-label, phase III study of a 28-day oral regimen of eniluracil plus fluorouracil versus intravenous fluorouracil plus leucovorin as first-line therapy in patients with metastatic/advanced colorectal cancer.

PURPOSE: To compare the efficacy and tolerability of eniluracil (EU)/fluorouracil (5-FU) with that of 5-FU/leucovorin (LV) as first-line therapy for patients with metastatic/advanced colorectal cancer. PATIENTS AND METHODS: This multicenter, randomized, open-label, phase III study (FUMA3008) conducted in the United States and Canada compared the safety and efficacy of EU/5-FU (11.5 mg/m(2)/1.15 mg/m(2) twice daily for 28 days every 35 days) with that of intravenous 5-FU/LV (425 mg/m(2)/20 mg/m(2) once daily for 5 days every 28 days) in patients with previously untreated metastatic colorectal cancer. Overall survival (OS) was the primary end point. RESULTS: A total of 981 patients were randomized and 964 patients received treatment (485 EU/5FU, 479 5FU/LV). Survival for EU/5-FU was not statistically equivalent (but not statistically inferior) to that for 5-FU/LV (hazard ratio, 0.880; 95% confidence interval [CI], 0.75 to 1.03). Median duration of survival was 13.3 months in the EU/5-FU group and 14.5 months in the 5-FU/LV group. Median duration of progression-free survival for EU/5-FU was statistically inferior to that of the control group (20.0 weeks [95% CI, 19.1 to 20.9 weeks] v 22.7 weeks [95% CI, 18.3 to 24.6 weeks]; P =.01). Both treatments were well tolerated. Diarrhea was the most common nonhematologic toxicity in both groups; treatment-related grade 3 or 4 diarrhea occurred in 19% of patients treated with EU/5-FU and 16% of patients receiving 5-FU/LV (P =.354). Grade 3 or 4 granulocytopenia occurred in 5% of EU/5-FU patients and 47% of 5-FU/LV patients. CONCLUSION: Safety profiles of both treatments were acceptable. Although antitumor activity was observed, EU/5-FU did not meet the protocol-specified statistical criteria for equivalence to 5-FU/LV in terms of OS.

Administration, Oral↗

PubMed2002

Radioembolization for hepatic metastases.

In a phase I/II study, 37 patients with metastatic liver disease, predominantly from colorectal cancer (n = 33) were treated between 1986 and 1994 by intrahepatic arterial embolization of radioactive yttrium 90 (Y 90) glass microspheres. The calculated total liver dose increased in stages from 5,000 cGy to 15,000 cGy. Mean follow-up was 8 months (range, 1 to 49). No major procedural, hematologic, or pulmonary complications occurred. Late gastroduodenal ulceration occurred early in the study at 6 to 8 weeks in three patients with a history of chronic alcohol abuse and was treated successfully medically. Of 30 patients with either computed tomography (CT) or sonography follow-up for 4 months or longer, 15 had tumor involvement in the liver that was diffuse, irregular, or infiltrating with mixed or poor vascularity and thus definitive imaging changes could not be appreciated on follow-up. In 15 patients with identifiable marker lesions with developed hypervascularity, post-treatment beneficial effects were noted. In seven of these patients followed by CT, decreased tumor attenuation and sharper definition of tumor-liver interface were noted. Findings on sonography in eight patients were increased tumor sonolucency centrally, consistent with liquefaction necrosis, and rim hyperechogenicity, consistent with calcification. A 25% to 40% decrease in area of marker lesions occurred in five patients and one other patient had small 1.0- to 1.5-cm lesions disappear temporarily on sonography. In conclusion, this method provides a feasible single-session technique for treatment of hepatic metastases. Complications are low and if the tumor pattern is nodular with some hypervascularity, beneficial effects are observed clinically and on imaging studies.

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