Phase II trial of 5-fluorouracil plus eniluracil in patients with advanced pancreatic cancer: a Southwest Oncology Group study.

BACKGROUND: Eniluracil is a potent, irreversible inactivator of dihydropyrimidine dehydrogenase, the major catabolic enzyme for 5-fluorouracil (5-FU). Pretreatment with eniluracil significantly increases plasma half-life, plasma concentration and oral bioavailability of 5-FU. This multicenter phase II trial was designed to estimate the 6-month survival rate in patients with metastatic adenocarcinoma of the pancreas treated with 5-FU and eniluracil. PATIENTS AND METHODS: One hundred and sixteen patients (61 with no prior chemotherapy and 55 with prior chemotherapy) were registered for treatment with eniluracil 50 mg (total dose) p.o. on days 1-7 and 5-FU 20 mg/m(2)/day p.o. on days 2-6 of a 28-day treatment cycle. RESULTS: In 106 patients evaluable for survival, the 6-month survival rate was 34% [95% confidence interval (CI) 22% to 47%, median survival 3.6 months] for patients who had not been treated previously with chemotherapy and 29% (95% CI 16% to 42%, median survival 3.4 months) for those who had received prior chemotherapy. For those patients with measurable disease, the confirmed response rates were 8% and 2%, respectively. The most common grade 3-4 toxicities were neutropenia (29% of patients) and diarrhea (12% of patients). Overall, 69% of patients experienced a grade 3 or worse adverse event during treatment. CONCLUSIONS: These results suggest that the combination of a 7-day course of eniluracil and a 5-day course of oral 5-FU has limited activity in patients with advanced pancreatic cancer, and is associated with a high frequency of clinically significant adverse events.

Phase II evaluation of suramin in advanced renal cell carcinoma. A Southwest Oncology Group study.

Twenty-two eligible patients with advanced renal carcinoma were treated with suramin utilizing a fixed dose regimen. Therapy was reasonably well tolerated with 3 of 22 patients (14%) developing grade 4 toxicity and 11 of 22 patients (50%) having a maximum toxicity of grade 3. There were no responders; median survival was 10 months. Suramin is not an active agent in advanced renal carcinoma.

Amphotericin B modifications of peripheral blood lymphocyte and tonsil lymphocyte responses to concanavalin A.

Peripheral blood lymphocytes (PBL) were shown previously to be activated to incorporate 3H-thymidine by concanavalin A (con A). Amphotericin B (Am B) was reported to be both immuno-enhancing and suppressive. We investigated the response of PBL and tonsil lymphocytes (TL) to con A in culture, and the effect of Am B on these responses. PBL were activated by con A as expected, and the magnitude of the response diminished as cell density increased. The responses of PBL usually were significantly enhanced by Am B at 2.5 or 5 micrograms/ml, but 10 micrograms Am B/ml significantly inhibited the con A response. TL had relatively high rates of spontaneous proliferation, but Am B was a potent inhibitor of this. TL responded to con A just as well as PBL, and Am B strongly inhibited these responses too. When TL were cultured with various doses of con A in the presence of 5 or 10 micrograms Am B/ml, the shape of the dose curves resembled those of PBL stimulated in the absence of Am B except that the incorporation of 3H-thymidine increased with increasing cell density. It was concluded that Am B at 2.5-5.0 micrograms/ml enhanced the response of PBL to con A and suppressed the response at 10 micrograms/ml. All doses of Am B inhibited both spontaneous proliferation and con A-induced proliferation in TL. In spite of this inhibition, the TL population responded to various doses of con A in the presence of Am B.