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Background. UFT is a fixed-ratio combination of uracil and Ftorafur, a prodrug that is absorbed orally and metabolized in vivo to 5-fluorouracil (5-FU). Uracil potentiates 5-FU through interference with its catabolism. The combination of UFT and leucovorin in patients with advanced incurable colorectal cancer, to evaluate preliminary activity and toxicity in this patient population. Methods. Twenty-one patients were treated. Twenty patients were evaluable for toxicity and response. Patients received UFT 350 mg/m2/day divided every 8 hours. Patients took a 5 mg tablet of leucovorin every 8 hours, concurrent with each UFT dose. Treatment was continued for 28 consecutive days, followed by a 7-day rest. Results. Five major objective responses (one complete and four partial) were observed. Toxicity was mild, with no dose-limiting myelosuppression. Four patients experienced grade 3 diarrhea or higher, and two patients experienced dose-limiting mucositis. Conclusion. UFT and low dose leucovorin is a well tolerated, orally administered regimen with activity in colorectal cancer. A randomized comparison of this regimen with conventional parenteral regimens is warranted.

Background. No effective systemic salvage therapy exists for patients with advanced colorectal cancer who progress after receiving bolus fluorouracil (FU) and leucovorin (LV) chemotherapy. In vitro data suggest that bolus FU resistance can be overcome by continuous infusion (CI) FU, and that the cytotoxic effects of Mitomycin-C (MMC) and FU are synergistic. Based on this data, a Phase II trial of CI FU and LV with bolus MMC in patients with advanced colorectal carcinoma who progressed on only one previous chemotherapy regimen was performed. Methods. Twenty-eight patients with advanced colorectal carcinoma who had progressed after one previous chemotherapy regimen of bolus FU/LV were treated with bolus MMC 10 mg/[m.sup.2] every 6 weeks and CI FU 200 mg/ [m.sup.2]/day admixed with LV 10 mg/[m.sup.2]/day given 14 days on/7 days off. Results. The partial response rate in 24 evaluable patients was 17% (95% confidence interval, 2-32%) with a median response duration of 9.5 months (range, 4.2-12.0 months). Twelve (50%) additional patients achieved disease stabilization. Median survival was 9.9 months in the whole group (28 patients) and 11.5 months in the 24 evaluable patients. The major toxicities were grade 4 diarrhea occurring in two patients and grade 3 mucositis occurring in five patients. There was minimal myelosuppression (grade 3 thrombocytopenia in one patient) and no occurrences of hand-foot syndrome or cardiotoxicity. Conclusions. This regimen demonstrates modest activity with acceptable toxicity in colorectal cancer patients who have failed a single-bolus FU/LV regimen. Modifications of this and other infusional FU-based chemotherapy regimens should be explored as potential salvage chemotherapy regimens in advanced colorectal cancer.

Background. We studied three new dose schedules of hepatic arterial infusion of floxuridine (FUDR) and leucovorin and update survival analysis of a previously reported trial using these drugs by hepatic arterial infusion for patients with hepatic metastases from colorectal carcinoma. Methods. Untreated patients with hepatic metastases from colorectal cancer were treated with three dose schedules: Group D, FUDR (0.3 mg/kg/day) and leucovorin (30 mg/[m.sup.2]/day) as a 14-day continuous infusion through an implantable hepatic arterial pump alternating with a 4-week rest period; Group E, a lower dose of FUDR (0.25 mg/kg/day) and leucovorin (30 mg/[m.sup.2]/day) as a 14-day infusion alternating with 2 weeks of saline; and Group F, FUDR (0.3 mg/kg/day) with a lower leucovorin dose (15 mg/[m.sup.2]/day) for 2 weeks followed by a 2-week rest. Results. In 42 patients with unresectable hepatic metastases, the complete-plus-partial response rate was 56%, with a median survival of 24.2 months. Completeplus-partial response rates for groups D, E, and F were 30%, 54%, and 75%, respectively. Twelve percent of the 42 patients developed biliary sclerosis; the percentages of patients per group were 17%, 15%, and 6%, respectively. Updated median survival of the original 24 patients treated with FUDR and leucovorin by hepatic arterial infusion and these 42 new patients (66 total) was 28.8 months. One-, two-, three-, four-, and five-year survival rates were 86%, 62%, 31%, 15%, and 7%, respectively. Conclusions. Hepatic arterial chemotherapy with FUDR and leucovorin for patients with hepatic metastases from colorectal carcinoma yields a high response rate and 1-and 2-year survivals of 86% and 62%, respectively. Although a lower dose of leucovorin (15 mg/[m.sup.2]) with FUDR produces a high response rate with less toxicity, before larger scale trials are initiated, further investigation is needed to reduce toxicity. A study of hepatic arterial dexamethasone with FUDR and leucovorin has been initiated for this purpose. Cancer 1994; 73:1134-42. Key words: floxuridine, leucovorin, colorectal neoplasms, hepatic neoplasms (secondary), hepatic arterial chemotherapy.

Background. A Phase I trial was performed to determine the maximum tolerated dose of concurrent preoperative radiation therapy (5040 cGy) and 2 cycles (bolus daily times 5) of 5-fluorouracil (5-FU) and low-dose leucovorin (LV) (20 Mg/[m.sup.2]), followed by surgery and 10 cycles of postoperative 5-FU/LV in patients with primary or recurrent rectal cancer. Methods. Twenty-four patients were entered into the study. Preoperatively, the initial dose of 5-FU was 325 mg/[m.sup.2]. 5-FU was escalated 50 mg/[m.sup.2], while the dose of LV and radiation therapy remained constant. Chemotherapy and radiation began concurrently on day 1. The post-operative chemotherapy was not dose escalated; 5-FU, 425 mg/[m.sup.2], and LV, 20 mg/[m.sup.2]. The median follow-up was 10 months (range, 4-19 months). Results. The resectability rate with negative margins in the 23 patients who underwent surgery was 100%. One patient refused surgery. The pathologic complete response rate was 13% (3 of 23). An additional four patients had negative nodes and a microscopic foci of tumor in the bowel wall. Therefore, the total clinical complete response rate was 30% (7 of 23). The maximum tolerated dose of 5-FU for the preoperative combined modality segment was 375 mg/[m.sup.2]; therefore, the recommended Phase II dose level is 325 mg/[m.sup.2]. The incidence of Grade 3+ toxicity for the 22 patients treated at the recommended 5-FU dose level (325 mg/[m.sup.2]) during the preoperative combined modality segment was as follows: diarrhea, 14%; erythema, 5%; hematologic, 10%; and total , 18%. The median nadir counts were leukocyte count, 3.7 (range, 1.5-5.9); hemoglobin count, 12.2 (range, 10.2-14.3); and platelet count (times 1000), 165 (range, 92-237). Conclusions. With this regimen, the recommended doses of chemotherapy in the combined modality segment are slightly higher than those recommended in arm 2 of the Intergroup postoperative adjuvant rectal trial 0114. This regimen will serve both as the preoperative arm of the Intergroup randomized trial of preoperative versus postoperative combined modality therapy for resectable rectal cancer (INT R9401) as well as the basis for the combined modality segment of NSABP RO-3. Cancer 1994; 73:273-8.

Background. Most patients with colorectal carcinoma metastatic to the liver have relapses after surgical resection of hepatic metastases with failures divided equally between hepatic and extrahepatic sites. A pilot study was begun using a regimen combining intrahepatic floxuridine (FUDR) and systemic 5-fluorouracil (5-FU) and leucovorin (LV) to determine its safety and efficacy. Methods. Because this was a pilot study, 21 patients with unresectable hepatic metastases from colorectal carcinoma were treated to assess the regimen's toxicity. Eight patients had liver metastases that were resected completely; then they received treatment. FUDR was given by hepatic arterial pump through a 14-day continuous infusion at 0.25 mg/kg/day. Systemic therapy consisted of LV 200 mg/[m.sup.2] and 5-FU 280 mg/[m.sup.2] using a bolus dose of 5-FU for 5 days with escalation of the 5-FU dose in separate patient cohorts. The maximally tolerated 5-FU dose was 325 mg/[m.sup.2]. Results. The median survival in the 21 unresectable patients was 16 months with a partial response rate of 56% (10 of 18 evaluable patients; 95% confidence interval, 38-79%). The major systemic toxicity was diarrhea, Grade 3 or 4, in 54% of patients being treated in the 4-week regimen and 19%, in the 5-week regimen. The level of hepatic toxicity was similar to that in previous studies using intrahepatic chemotherapy alone, i.e., 48% of patients had a 200% increase in alkaline phosphatase levels and 10% had bilirubin elevations of more than 3.0 mg/dl (one patient had documented biliary sclerosis). All eight patients treated with adjuvant therapy were alive without disease after a median follow-up of 23 months. Conclusions. Systemic 5-FU and LV can be combined safely with intraarterial FUDR without loss of efficacy or increased biliary toxicity. Eight patients treated with this regimen as adjuvant therapy after liver metastasis resection were alive and disease-free after a median follow-up of 23 months. Cancer 1993; 71:1964-71.

The predispostion of preexisting cirrhotic metabolic liver disease to the development of hepatocellular carcinoma is well established. However, the association between glycogenoses (a form of noncirrhotic metabolic liver disease) and the formation of benign and malignant liver tumors is less well known. The sixth case of simultaneous occurrence of glycogenosis type Ia and hepatocellular carcinoma, which occurred in a 34-year-old man referred for advice on therapy for his malignant neoplasm, is reported. Cases previously described in the literature are reviewed and management of this entity in light of the current knowledge in the diagnosis and treatment of hepatocellular carcinoma is discussed. Cancer 1992; 69:1320-1322.

With a listening typewriter what an author says would be automatically recognized and displayed in front of him or her. However, speech recognition is not yet advanced enough to provide people With a reliable listening typewriter. An aim of our experiments was to determine if an imperfect listening typewriter would be useful for composing letters. Participants dictated letters, either in isolated words or in consecutive word speech. They did this with stimulations of listening typewriters that recognized either a limited vocabulary (1000 or 5000 words) or an unlimited vocabulary. Results suggest that some versions, even upon first using (hem, could be at least as good as traditional methods of handwriting and dictating. Isolated word speech with large vocabularies may provide the basis for a useful listening typewriter. [ABSTRACT FROM AUTHOR]

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