ONCOLOGY Vol 11 No 9

Although the combination of uracil and tegafur (UFT) has been available commercially in Japan since 1984 and is one of the most extensively prescribed antineoplastic agents in that country, few physicians outside Japan have knowledge of and

Twenty-four patients with metastatic breast cancer that had progressed after high-dose chemotherapy with peripheral blood progenitor cell (PBPC) support were given intramuscular methotrexate in combination with oral

Both cisplatin (Platinol) and fluorouracil (5-FU) have demonstrated single-agent clinical efficacy in a variety of solid neoplasms. The combination of these agents has revealed synergistic cytotoxicity in models in vitro and in vivo, which may explain the clinical effectiveness of 5-FU-cisplatin regimens. UFT (tegafur and uracil) and bis-aceto-ammine-dichloro-cyclohexyl-amine platinum (IV) (JM-216) are novel oral analogues of 5-FU and cisplatin, respectively. In preclinical models, JM-216 has demonstrated equivalent cytotoxicity to cisplatin, while phase I trials suggest its dose-limiting toxicity is myelosuppression. In contrast to cisplatin, JM-216 has not demonstrated significant neurotoxicity or nephrotoxicity. UFT has been used extensively in Japan, where phase II data suggest disease response rates similar to single-agent 5-FU in colorectal, gastric, and breast carcinomas. Combination studies of prolonged administration UFT and single-dose cisplatin have shown efficacy, but also significant hematologic toxicity. We propose a phase I study of UFT and JM-216 administered daily over 14 consecutive days with leucovorin (90 mg/d). Ease of administration and continuous drug exposure are potential advantages of this regimen. Several disease specific investigations may be warranted given demonstrated feasibility in this phase I study.[ONCOLOGY 11(Suppl 10):26-29, 1997]

Given that no therapeutic methods of postoperative adjuvant chemotherapy for non-small-cell lung cancer have been established, we selected UFT (tegafur and uracil) for investigation because UFT is less injurious to the host

This phase III study compares leucovorin plus fluorouracil (5-FU) 425 mg/m2, days 1 through 5, 28-day cycle, with oral leucovorin plus oral UFT (tegafur and uracil) 300 mg/m2, days 1 through 28, 35-day cycle, in terms of

Despite recent progress in surgery and chemotherapy, advanced gastric cancer carries a poor prognosis. Although several antitumor agents have some clinical activity, responses are usually of short duration and fail to

Thirty-nine patients with locally advanced or metastatic gastric carcinoma received oral UFT (tegafur and uracil) plus leucovorin. Treatment consisted of UFT 360 mg/m2/day plus leucovorin 25 mg/m2/day, given orally in divided

Therapeutic options for patients with advanced colorectal cancer who have failed treatment with fluorouracil (5-FU) are limited. Responses have been reported in this setting with a protracted venous infusion of 5-FU. Daily oral therapy with tegafur and uracil (UFT) plus leucovorin (LV) has the potential to mimic the pharmacology of continuous infusion 5-FU. Therefore, we undertook a phase II study of a 28-day schedule of a combination chemotherapy regimen containing oral UFT/leucovorin in patients with measurable metastatic colorectal cancer who had failed treatment with bolus 5-FU. In addition, we sought to determine whether coadministration of UFT and leucovorin alters the bioavailability of these agents. In a pretreatment phase, each patient underwent sequential pharmacokinetic sampling following a single dose of UFT alone, leucovorin alone, and the combination of UFT plus leucovorin. The preliminary results of this trial suggest that tegafur pharmacokinetics are not affected by coadministration of leucovorin and that folate pharmacokinetics are not affected by UFT. [ONCOLOGY 11(Suppl 10):22-25, 1997]

To evaluate the significance of postoperative adjuvant chemotherapy using mitomycin C (MMC) and UFT (tegafur and uracil) in combination, the Japanese Foundation for Multidisciplinary Treatment of Cancer conducted a prospective randomized controlled trial with 834 patients who had undergone curative resection for rectal cancer (T3 or T4 tumors and/or N1, N2, or N3 disease). The patients were randomly allocated to a treatment group (MMC/UFT, 416 patients) and a control group (surgery only, 418 patients). For patients in the treatment group, 20 mg of MMC was sprinkled on the operating field upon completion of surgery. MMC was intravenously injected at 6 mg/m2 on day 7, and then each month after surgery for 6 months. UFT was administered orally at 400 mg/day for 1 year. Although no difference was observed in the 5-year survival rate between the two groups, the 5-year disease-free survival rate in the MMC/UFT group was 69.1%, which was significantly higher than in the control group (59.3%, P = .005). The 5-year cumulative local recurrence rate was significantly lower in the MMC/UFT group (11.6%) than in the control group (19.0%) (P = .0071). We conclude that the adjuvant use of long-term oral UFT and intermittent intravenous MMC improves the disease-free survival rate of patients with curatively resected rectal cancer. [ONCOLOGY 11(Suppl 10):40-43, 1997]

UFT (tegafur and uracil) has been studied extensively in Japan, with documented efficacy in hepatobiliary and pancreatic cancer. In the United States, UFT with or without leucovorin has not undergone phase II testing in

The selective antineoplastic effect of tegafur and uracil (UFT) is attributed to its preferential enhancement of fluorouracil concentration in tumor tissues compared with that in normal tissues. The result of this effect is evident in the clinical benefit and lower toxicity associated with UFT compared with other fluorinated pyrimidines. Beginning with preclinical studies in the 1980s, significant therapeutic advantages of UFT have been reported in numerous trials conducted in Japan, including phase I dose-finding studies, phase II multicenter studies, comparative studies, and combination-chemotherapy studies. In phase II studies conducted at 211 institutions, for example, it was shown that the response rate was over 30% in patients with head/neck, bladder, or breast cancer, and the survival rate was superior to that previously reported in Japanese studies. Two comparative studies suggested that UFT was more effective than single-agent tegafur, and a number of combination-chemotherapy studies have shown that it has an advantage in terms of toxicity, response, and/or survival. UFT is also useful for postoperative adjuvant therapy, as well as therapy for advanced disease in a variety of neoplasms. UFT holds considerable promise and future trials should continue the evaluation and refinement of its role in the treatment of cancer.[ONCOLOGY 11(Suppl 10):30-34, 1997]

Adjuvant chemotherapy has been shown to alter the natural history of patients with resected colon cancer. Two regimens (fluorouracil [5-FU] plus levamisole (Ergamisol) and 5-FU plus leucovorin) have been found most

Standard adjuvant therapy for transmural (T3) and/or node-positive rectal cancer is pelvic radiation therapy plus fluorouracil (5-FU)-based chemotherapy. Randomized trials are in progress to help determine the ideal

In a laboratory study using an experimental peritoneum model of gastrointestinal cancer, the UFTP [tegafur and uracil (UFT) plus cisplatin] regimen was shown to provide a survival benefit compared with the UFTM (UFT plus

The phase I development program of tegafur and uracil (UFT) in the United States has included evaluation of the drug as a single agent and subsequent studies of its biochemical modulation by oral leucovorin. Phase I trials of single-agent UFT examined both a 5-day schedule repeated every 21 days and a 28-day schedule repeated every 35 days. In all of the trials the total dose was divided by three and administered three times daily at 8-hour intervals. Like intravenous schedules of fluorouracil (5-FU), UFT has schedule-dependent toxicity, with granulocytopenia being the dose-limiting toxicity for the 5-day regimen and diarrhea being the dose-limiting toxicity for the 28-day regimen. The suggested phase II doses for UFT administered without leucovorin were 800 mg/m2/day for the 5-day schedule and 360 mg/m2/day for the 28-day schedule. Subsequent phase I studies combining UFT with oral leucovorin used a 28-day schedule repeated every 35 days. Diarrhea was the dose-limiting toxicity, and the recommended phase II dose was UFT, 300 mg/m2/day, plus leucovorin, 90 mg/day. Pharmacokinetic evaluation showed that single-dose UFT results in maximum plasma levels and an area under the concentration-time curve that increased with escalating UFT doses. In addition, 5-FU levels were detectable throughout the 28-day dosing period; however, there was no evidence of significant accumulation of uracil, tegafur, or 5-FU. The administration of leucovorin in this trial provided continuous exposure of d,l-leucovorin and 5-methyltetrahydrofolate with little variation between doses or days.[ONCOLOGY 11(Suppl 10):35-39, 1997]

Gastric cancer is the most chemosensitive adenocarcinoma among digestive neoplasms. A few years ago, we performed a phase II trial with the FLEP regimen, in which fluorouracil (5-FU) and leucovorin are combined

Several trials performed in the United States and Europe have demonstrated the efficacy of UFT (uracil and tegafur in a 4:1 molar combination) with oral leucovorin in the treatment of several tumor types, but particularly

A single-institution phase II study indicated that combination chemotherapy using UFT (tegafur and uracil) plus cisplatin (Platinol) in patients with non-small-cell lung cancer was active with less host toxicity than other cisplatin-

Fujii et al reported that Uracil potentiated the antitumor activity of fluorouracil (5-FU) and 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur). This effect was due to inhibition of the degradation of 5-FU, yet the phosphorylation of 5-FU was unaffected. The molar ratio of tegafur and uracil was 1:4, a combination that has since been widely prescribed in Japan for the treatment of cancer patients. We present here our experimental and clinical results when investigating the antineoplastic effects of this combination of drugs-known as UFT-and provide evidence that UFT is an effective treatment for patients with cancer. [ONCOLOGY 11(Suppl 10):14-21, 1997]

Between 1989 and 1993, 409 evaluable patients with breast cancer have been treated with tegafur and uracil (UFT) in an adjuvant setting in two different trials. Data from both trials were reviewed in December 1995 after a

An open-label, randomized phase III trial has been established to compare the efficacy and safety profile of tegafur and uracil (UFT) plus leucovorin with fluorouracil (5-FU) plus leucovorin as first-line chemotherapy for

During the 1990s, one in nine women in the western world will be diagnosed with breast cancer, and more than 58,000 will die of the disease each year in Europe alone. Recent changes in the primary therapy of operable

The escalating role played by managed care organizations in the health-care system is reflected in the increased demand for cost-effectiveness analyses (CEAs) to assess the balance between economic impact

This study compared the activity and toxicity of fluorouracil (5-FU)/cisplatin with the combination tegafur and uracil (UFT)/cisplatin in the neoadjuvant treatment of locally advanced-stage III or IV (M0)-head and neck

Squamous cell carcinoma of the head and neck is a potentially curable neoplasm. Historically, the standard approach to treatment has been either surgery or radiation therapy, or a combination of the two. Over the past

The oral fluoropyrimidines have proved to be active in colorectal cancer in Japan and, recently, in the United States and Europe. Continuous oral administration simulates protracted fluorouracil (5-FU) continuous

The article by O'Donovan discusses the radiologic appearance of lung cancer, with particular emphasis on the radiographic appearance and work-up of solitary pulmonary nodules (SPNs).

A staple of summer, the common housefly may be a reservoir for Helicobacter pylori, the bacterium responsible for some

Cancer Care, Inc., a voluntary cancer agency dedicated to providing supportive services for people with cancer and their families, is providing copies of Cancer Care Briefs-single-page information sheets that help cancer patients cope with their

The map shown in Figure 1 provides the annual rates of acquired immunodeficiency syndrome (AIDS) per 100,000 population, by state of residence from January through December 1996. Table 1 lists the metropolitan areas with the 50