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Background: Floxuridine (FUDR) and alpha-interferon (IFN) are active agents in advanced renal cell carcinoma, with different dose-limiting toxic effects and antitumor synergism in experimental models. The main purpose of this phase II study was to assess the activity and toxic effects of a combination of FUDR and alpha 2b-IFN in metastatic renal cell carcinoma., Patients and Methods: Metastatic renal cell carcinoma patients with measurable disease entered the study. FUDR was administered as a constant-rate continuous infusion for 14 days every 28 days at a starting daily dose of 0.1 mg/kg and with dose escalations of 0.025 mg/kg/day at each subsequent cycle if WHO > or = 2 toxicity had not occurred. IFN-alpha 2b 10 x 10(6) I.U. was administered intramuscularly 3 times per week., Results: Forty-two patients entered the study and a total of 272 cycles of FUDR + alpha 2b-IFN were administered. In 41 evaluable patients WHO grade III-IV toxic effects included nausea and vomiting (22%), diarrhea (32%), stomatitis (12%), fatigue (27%) and anorexia (12%). It was possible to increase the initial FUDR does in 21 (50%) patients; the median FUDR dose intensity was 0.35 mg/kg/week (range 0.18-0.54). Among 39 evaluable patients, 3 (7.5%) complete and 10 (25.5%) partial responses were observed (response rate 33%, 95% confidence interval (CI) 19%-50%) which lasted a median of 13 months (5.5-40+). Responses also occurred in liver (2), in patients pretreated with systemic therapy (5) and in patients who had other unfavourable prognostic characteristics (7). Median progression-free and survival times were 9 and 16 months, respectively., Conclusions: In this study FUDR + alpha 2b-IFN demonstrated interesting activity in metastatic renal cell carcinoma, showing promise also in patients with unfavourable prognostic characteristics. The antitumor activity of FUDR and alpha 2b-IFN seems to be cumulative, but cumulative toxicity is also observed. These results require confirmation in randomised trials.

Background: Cancer chemotherapy in elderly patients is an important and under-researched area. Doxifluridine is a fluoropyrimidine derivative and is activated to 5-fluorouracil by uridine phosphorylase, which is more highly expressed in malignant cells. Because of the high bioavailability and low toxicity of oral doxifluridine we conducted this phase II trial to evaluate the feasibility, toxicity and activity of a home therapy with oral doxifluridine in elderly metastatic colorectal cancer patients., Patients and Methods: Forty-three elderly metastatic colorectal cancer patients entered the study: their median ECOG performance status was 1 (0-2) and median age 74 years (69-83), the predominant site of metastasis was liver and all but one of the patients had received no previous chemotherapy. Doxifluridine was given orally at the initial daily total dose of 2250 mg for 4 consecutive days every week. The daily dose was reduced to 1500 mg if toxicities greater than grade 2 (WHO) occurred., Results: Forty-two patients are evaluable for toxicity: treatment was well tolerated, with the most common side effect being diarrhea, severe in 7 (17%) patients (6 grade 3 and 1 grade 4). Thirty-six patients are evaluable for response and 2 complete and 3 partial responses have been observed (response rate 14%; 95% confidence limit interval 5%-29%)., Conclusions: This study demonstrates that a home therapy with oral doxifluridine in elderly advanced colorectal cancer patients is feasible, with a relatively low rate of toxicity, and has moderate activity, comparable to that of intravenous 5-fluorouracil. Therefore, this treatment may be considered for the management of advanced colorectal cancer in the elderly.