Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leucovorin, given usually by i.v. injection or orally changes to 5, 10-methylene tetrahydrofolate in tumor as well as normal cells. And in normal FdUMP, an active metabolite of 5-FU, binds tightly to thymidylate synthase in the presence of cofactor, 5, 10-methylene tetrahydrofolate. This interaction leads to potentiate the cytotoxic effect of 5-FU by prolonged inhibition of thymidylate synthase. Phase I study using l-leucovorin (l-LV), an active form of leucovorin, combined with 5-FU, was conducted. In the weekly schedule, 5-FU was fixed to 600mg/m2, and l-LV dose was escalated from 125 mg/m2 to 250mg/m2, if toxicity was acceptable. On the other hand, in the five consecutive-day schedule, 5-FU was fixed to 370mg/m2 and l-LV was escalated from 25mg/m2 to 50mg/m2, 100mg/m2 and 200 mg/m2. l-LV 10mg/m2 was tested as reference. On weekly schedule of l-LV 250mg/m2, grade III diarrhea was seen in 2 cases and grade IV leucopenia was seen in one. In five consecutive-day schedule, at each dose of l-LV, stomatitis, nausea plus vomiting, anorexia, anemia and leucopenia were seen. However, the increase of toxicities were not seen by dose escalation of l-LV. Then, we have been conducted a randomized early phase II study using 250 mg/m2 of l-LV weekly (arm A) and 100mg/m2 (arm B) or 10mg/m2 (arm C) of l-LV for 5 consecutive days in gastric and colorectal cancer by multicenter cooperative study. Plasma concentrations of l-LV were maintained > 10(-5) mol/L for over 5 hrs. after 2 hrs. infusion of 250 mg/m2 of l-LV and for over one hr. after a rapid injection of 100mg/m2 of l-LV.
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PMID:[Phase I study of 5-fluorouracil and l-leucovorin]. 845 86

Thirty-seven patients with advanced colorectal cancer were treated with fluorouracil (5-FU) and folinic acid (FA) (Jan 1990-Dec 1992). Clinical assessment and administration of chemotherapy was incorporated as part of the daily work load of a busy general surgical unit. Records were available for all 37 patients and showed that 13 patients (Treatment failures, Group B) failed to receive more than 3 monthly cycles of treatment, while the remaining 24 received 6 or greater cycles (Treatment completed, Group A). There was no survival advantage demonstrated for the complete study cohort (n = 37) when compared to an historical group (n = 1038) of untreated patients. Median survival in Group A (14.2 months) was significantly greater (chi-squared, P < 0.0001) than survival in Group B (6.7 months). Toxicity was common with 43% experiencing mouth ulcers or stomatitis (13% severe). Three per cent had dose-limiting diarrhoea and myelotoxicity was minimal. There were six partial responses and 16 patients had no change in their disease status while on treatment. Current regimen of 5-FU/FA are well-tolerated with low toxicity but show no survival advantage for advanced colorectal cancer. However, these regimens may be administered within the confines of general surgical practice.
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PMID:Advanced colorectal cancer treated with combined 5-fluorouracil and folinic acid: the experience within a surgical department. 863 15

This study was conducted to establish the optimum postoperative adjuvant chemotherapy with 5-FU in patients with gastric cancer. Seventy gastric cancer patients were treated after surgery with one of the following regimens; 5-FU 10 mg/kg/24 hrs c.i.v. x 24 days (arm A, n = 25); 5-FU 20 mg/kg/24 hrs c.i.v. x 4 days/w x 3 courses (arm B, n = 16); 5-FU 30 mg/kg/24 hrs c.i.v. x 2 days/w x 4 courses (arm C, n = 25). Blood 5-FU concentration, adverse effects and prognosis in each arm were compared. Changes in blood 5-FU concentrations were dose-related. The three-year survival rates in arms A, B and C were 15.0, 13.5 and 0.0%, respectively; they tended to be greater in arms A and B, but differences were not statistically significant. The most frequent adverse effects of the treatments were gastrointestinal, such as stomatitis. The incidence of reactions tended to be low in arm C, i.e., high-dose intermittent administration. Arm B (4 days-on, 3 days-off) was modified to 4 days-on, 6 days-off (arm B'), because severe stomatitis developed. The severity and incidence of stomatitis were reduced in the modified arm B group. We believe that intensive postoperative adjuvant chemotherapy for patients with gastric cancer should be designed using the arm B' approach.
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PMID:[Administration and dosage of fluorouracil (5-FU) continuous i.v. infusion in patients with non-curative resected/non-resected gastric cancer]. 867 14

The relatively high response rate demonstrated with the use of continuous infusion 5-Fluorouracil (CIFU) 200 to 300 mg/m2 per day in disseminated colon cancer is the rationale behind a NCI-sponsored intergroup trial (INT 0153) for postoperative adjuvant therapy of stage III colon cancer. Because CIFU necessitates a significant reduction in the dose of the modulator leucovorin compared with bolus 5-FU, a pilot study of continuous infusion 5-FU in several doses with levamisole was conducted to determine any unexpected toxicity of this combination, and to assess completion rates of levamisole was conducted to determine any unexpected toxicity of this combination, and to assess completion rates of this dose intensive schedule. CIFU, scheduled as two 12-week cycles, was administered at 250 mg/m2 per day. Pending toxicity at the initial dose, CIFU was to be escalated (300 mg/m2) or de-escalated (200 mg/m2). All but one patient entered on this trial completed 24 weeks of adjuvant CIFU+levamisole. Eight patients (57%) completed 24 weeks of therapy with the 2-week scheduled break. One of these 8 patients required a dose reduction without interrupting the schedule. Six patients had toxicity from the CIFU, which obliged us to interrupt the schedule. Limiting toxicities were stomatitis and hand-foot syndrome. No dose-limiting hematologic toxicity was encountered. Three patients (21%) had catheter problems that required replacement. These data suggest that up to 30% of patients started on this regimen may require dose reduction, shorter infusion courses with rest breaks, or both to complete 24 weeks of adjuvant treatment in order to achieve desired dose intensity.
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PMID:A pilot trial of continuous infusion 5-fluorouracil with levamisole for adjuvant therapy of colon cancer. 880 55

To evaluate ambulatory cancer chemotherapy, the clinical response, toxicities and survival time were analysed among 32 patients with non-curative or recurrent colorectal cancer who were treated by l-Leucovorin (l-LV) plus 5-fluorouracil for the past four years. Twenty-nine patients were treated with 5-FU (370 mg/m2) plus l-LV (10-100 mg/m2) for 5 consecutive days and a 23-day interval between treatments. Three patients were treated with l-LV (250 mg/m2) administered as a two-hour infusion and 5-FU (600 mg/m2) intravenous push midinfusion weekly for 6 weeks of an 8-week cycle. Partial response (PR) was observed in 9 patients (28%), no change (NC) in 18. One-year survival ratio was 61% and 4 of 32 patients survived at the end of this study. The median survival time was 14 months. Although stomatitis, nausea/vomiting, diarrhea, leukopenia and pigmentation were noted, no severe side effects were observed. These results suggested that l-LV plus 5-FU therapy might be a useful ambulatory cancer chemotherapy for patients with advanced colorectal cancer.
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PMID:[Clinical study of ambulatory cancer chemotherapy for advanced colorectal cancer]. 884 91

FEC (5-FU 500 mg/m2, epirubicin 50 mg/m2, and cyclophosphamide 500 mg/m2) administered as a conventional bolus schedule is widely used in treatment of advanced breast cancer. 5-FU is thought to be more efficient when administered at high doses as a continuous infusion. The aim of this study was to compare the response rate, time to treatment failure, and overall survival obtained with standard FEC regimen (group A) and FEC with high-dose infusional 5-FU (750 mg/m2 per day/days 1 to 5) (group B). One hundred and seventy-eight patients entered this study, 89 in each arm; 10 were noneligible. Both groups were comparable for age, performance status, menopausal status, hormonal receptor status and prior treatment of the initial tumor, duration of relapse free interval, and type and number of disease sites. One hundred and forth patients were evaluable for efficacy. The response rate was 33.3% in group A (1.4% complete response-CR), and 39.4% in group B (9.8% CR) (ns). In an intent to treat basis (n = 168) the response rates were 26.8% and 34.1%, respectively, in groups A and B (ns). The response rate in liver metastasis was significantly higher in group B (57.1%) than in group A (20.0%) (P = 0.03). The time to treatment failure and overall survival were not different between the two groups. One hundred and fifty-three patients were evaluable for toxicity. 10.7% of the patients in group A and 16.0% in group B stopped treatment due to toxicity. Stomatitis was more frequently observed in group B than in group A (46.7% versus 2.6%, respectively, p < 10(-9)). The rates of other side effects were similar in the two groups. In conclusion, the two regimens gave similar overall response rates, time to treatment failure and survival, but infusional 5-FU yielded a better response rate in the liver metastasis.
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PMID:Randomized trial comparing conventional intravenous bolus FEC and FEC with high-dose infusional 5-fluorouracil as first-line treatment of advanced breast cancer. 893 28

We previously reported results of a Phase II trial of UFT [Taiho Pharmaceutical Ltd., Tokyo, Japan; (BMS-200604) Bristol-Myers Squibb, Princeton, NJ], an oral 4:1 molar concentration of uracil and tegafur, plus oral leucovorin for metastatic colorectal carcinoma (Pazdur et al., J. Clin. Oncol. 12:2296-2300, 1994]. Our results demonstrated that a 28-day schedule of this combination produced a response rate similar to that obtained with conventional intravenous fluorouracil (5-FU)-plus-leucovorin regimens but without the severe or life-threatening neutropenia or oral mucositis that complicates intravenous 5-FU regimens. The current Phase I trial examines the dose-limiting toxic effects and maximum tolerated dose of a 14-consecutive-day schedule of UFT plus oral leucovorin in 14 patients who had histologically proven cancer and had received prior chemotherapy. The daily UFT plus leucovorin dose was divided into three doses administered orally every 8 hours. In this study, the UFT dose was escalated while the leucovorin dose remained at 150 mg/day. Of the 14 patients, 4 were initially treated at the 350-mg/m2/day UFT level for 14 days without any dose-limiting toxic reactions. Subsequently, another 7 patients were treated at the 400-mg/m2/day level; grade 3 diarrhea developed in 3 of these 7 (with severe abdominal cramping in 2 cases and severe nausea and vomiting unresponsive to antiemetics in the third). To better define the starting dose for phase II studies, an additional 3 patients were treated at the 350-mg/m2/day dose level. Of the total 7 patients treated at 350 mg/m2/day, grade 3 toxic events (diarrhea) developed in 2 patients. Grade 1-2 toxic effects noted at this level included fatigue, stomatitis, skin rash, abdominal pain, nausea, and vomiting. Neither partial nor complete responses were observed in this trial. The maximum tolerated dose of this schedule is 350 mg/m2/day UFT plus 150 mg/day oral leucovorin. However, because of this schedule's inferior dose intensity compared with that of the 28-day schedule of UFT plus leucovorin, subsequent development of UFT in the United States has focused on the 28-day regimen.
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PMID:Phase I trial of uracil-tegafur (UFT) plus oral leucovorin: 14-day schedule. 922 Feb 91

A total of 55 patients with measurable colorectal metastatic carcinoma were studied to evaluate the impact on toxicity, response, and survival of protracted venous infusion (PVI) 5-FU 200 mg/m2 per day with Cis-DDP 80 mg/m2 or carboplatin 300 mg/m2 every 3 weeks, 1-hour infusion. Patients received continuous uninterrupted therapy until there were signs or symptoms of toxicity. Both 5-FU and cisplatin were withheld when patients experienced grade II stomatitis and diarrhea, severe nausea or vomiting not controlled by standard antiemetic therapy, and clinically significant hand-foot syndrome. The toxicity was neurological (20% grade 2 and 3) hematological (13% grade 2) and dermatological (11% grade 2). The overall response (CR+PR) was 24% with a median survival of 13 months. The results of our study show that there is no improvement in response rate, response duration or survival compared with historical trials. However, this study does confirm the valuable palliative role of the protracted 5-FU infusion treatment. Colorectal carcinoma is one of the most common neoplasms in Western societies, being second only to lung cancer as a cause of death from malignancy. The management of nonmetastatic primary disease in surgical, with adjuvant chemotherapy for those at high risk of relapse. However, for those with metastatic disease at diagnosis or recurrent disease after resection, cytotoxic chemotherapy is the treatment of choice and fluorouracil (5-FU) is the most active cytotoxic agent in this disease, with a response rate of approximately 20%. Efforts to improve the response rate have focused on the use of agents to modulate 5 FU. The Southwestern Oncology Group (SWOG) study reported by Leichman et al. (1) and a study from the United Kingdom by Hill et al. (2) compared conventional FU to modulated FU and found no improvement in response rate or survival. In the SWOG study, two different schedules of bolus FU and LV were compared with bolus FU alone and to continuous infusion FU administered alone or modulated by LV or PALA. In this study, the results obtained with bolus FU were superior to most of the studies in the literature: The response rate was 26%, and the median survival was 14 months. The high- and low-dose LV and FU groups showed response rates and survival similar to bolus FU alone. However, in 12 previously reported randomized studies comparing FU and LV or FU alone, nine reported that the combination of FU and LV produced significant increases in response rates and two reported significant increase in survival (3, 4). Many of these trials used the dose schedules reported in the SWOG trial. Protracted venous infusion (PVI) 5-FU has been shown to have superior efficacy with less toxicity in colorectal cancer when compared to bolus 5-FU and synergy between cisplatin and 5-FU has been demonstrated in vitro. Consequently, we have investigated the efficacy of the combination of bolus cis or carboplatin and PVI 5 FU in 55 patients with advanced colorectal cancer using survival, response rate, symptomatic response, and toxicity as study endpoints.
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PMID:First-line protracted venous infusion fluorouracil with CisDDP or carboplatin in advanced colorectal cancer. 922 28

Phase II study of nedaplatin (NDP), a new derivative of cisplatin, was completed in 1990, so this agent is now commercially available. NDP is very effective for head and neck cancer. Out of the 90 evaluable patients, CR was achieved in 11 patients and PR in 27 with a response rate of 42%. A new combination chemotherapy containing NDP, especially NDP + 5-FU, was clinically tried. Furthermore concurrent NDP and radiotherapy will be tried in the near future. Phase II study of S-1 (tegafur + CDHP + Oxo) and taxotere (TXT), however, is ongoing. The results obtained so far are almost satisfactory. The aouthor also adopted several new agents which were presented at the ASCO meeting (1993-1997): taxol (TXL), taxotere (TXT), topotecan, amonafide, vinorelbine and thymitaq. Response rates of these agents were as follows: TXL: 26-37%, TXT: 27-41%, topotecan: 0-27%, vinorelbine: 6.7-12.5%, thymitaq: 18.2% and amonafide: 3.6%. So TXL and TXT are very effective for head and neck cancer. In terms of combination chemotherapy, response rates are 33-71% in TXL + CDDP, 23-62% in TXL + CBDCA, 78% in TXT + CDDP and 75% in TXT + CDDP + 5-FU. Concurrent radiotherapy and chemotherapy including new agents are interesting and important issues. Two kinds of protocol were adopted, 5-FU + HU + TXL + RT and TXL + CBDCA + RT. Both protocols are responsive to squamous cell carcinoma of the head and neck. But severe local toxicity (stomatitis) and bone marrow suppression pose problems.
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PMID:[Head and neck cancer]. 935 Feb 34

Fourteen patients with unresectable primary or metastatic liver cancer were divided into two groups: group A, continuous hepatic arterial infusion of 5-FU in 10 cases; group V, continuous intravenous infusion of 5-FU in 4 cases. In group A, 5-FU (360 mg/m2/day x 5 days/week x 4 weeks) was continuously infused into the hepatic artery via femoral or gastroduodenal artery through Infuse A Port. In group V, 5-FU (360 mg/m2/day x 2 weeks) was continuously infused into the subclavian vein through IVH route. On day 1, the concentration of 5-FU in peripheral blood in group A (12.1 +/- 12.8 ng/ml) was significantly lower than in group V (43.8 +/- 19.8 ng/ml, p = 0.004). On day 5, it was also decreased in group A (24.6 +/- 24.1 ng/ml) compared with that in group V (61.8 +/- 34.4 ng/ml, p = 0.039). Side effects of 5-FU like nausea, abdominal discomfort and stomatitis were recognized in 4 out of 10 patients in group A (40%) and 3 out of 4 patients in group V (75%). In group A, a complete response was obtained in one patient with synchronous multiple liver metastases of sigmoid colon cancer. These results suggest that systemic toxicity of 5-FU is alleviated by continuous hepatic arterial infusion in the patients with unresectable liver cancer because of its low concentration in peripheral blood.
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PMID:[Evaluation of 5-fluorouracil concentration in peripheral blood and side effects in continuous hepatic arterial infusion chemotherapy for patients with unresectable liver cancer]. 938 45


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