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)

The results of recent preclinical and clinical studies suggest that AO-90, a methionine-free intravenous amino acid solution (7.43%), potentiates the antitumor effect of 5-fluorouracil (5-FU). In the present multi-center, randomized, controlled study conducted at the internal medicine departments of 24 institutions between July 1991 and May 1993, patients with advanced gastric cancer were randomly allocated to receive either AO-90 (500-750 mL/day, AO/MF group) or Amiparen, a commercial intravenous amino acid solution (600-800 mL/day, C/MF group) by total parenteral nutrition for 14 days. Both groups received MF therapy which consisted of a continuous infusion of 5-FU at 350 mg/m2/day for 14 days and an i.v. push of mitomycin C 7 mg/m2 on days 7 and 14 (one course). Additional treatment courses were initiated after a withdrawal period when appropriate. Of the 53 subjects enrolled, 52 (98.1%) were eligible and 47 (88.7%) completed the scheduled treatment (AO/MF group: 23, C/MF group: 24). Although there were significant differences for age and sex between the groups, the Mantel-Haenszel test showed that these unevenly distributed characteristics did not affect the study results. The overall clinical response rates in the completed cases were 30.4% (7/23) in the AO/MF group and 16.7% (4/24) in the C/MF group. In particular, the response rate in the inoperable advanced cases with liver metastases, ascites or distant metastases was 45.5% (5/11) in the AO/MF group versus 16.7% (2/12) in the C/MF group. The treatment-related adverse reactions observed were mainly hematologic and subjective/objective symptoms, such as decreased leukocyte count, hemoglobin level and platelet count, nausea/vomiting, diarrhea, stomatitis, and fever. The differences in the incidence were not significant between the groups. These results show that AO-90 in combination with MF therapy is efficacious in the treatment of patients with gastric cancer.
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PMID:[A controlled study of AO-90, a methionine-free intravenous amino acid solution, in combination with 5-fluorouracil and mitomycin C in advanced gastric cancer patients (internal medicine group evaluation)]. 775 84

Between September 1990 and August 1994, 11 patients (pts) with liver metastases (mets) from colorectal cancer were treated with continuous hepatic arterial infusion chemotherapy of 5-fluorouracil (FU) plus leucovorin (LV). Eight pts had non-resectable liver mets (H3: 7, H2: 1), and 3 had residual small mets after resection of major mets. Drugs were administered via an extracorporeal infusion device connected to the hepatic arterial infusion port. 5-FU and LV were given through a 5- to 7-day continuous infusion at 500-750 mg/body/day and 30 mg/body/day, respectively, with a 3- to 4-week rest period. In the recent 6 pts, cisplatin was administered as a 2-hour infusion at 25 mg/body, one or two times simultaneously. Grade 2 toxicity was noted in two pts (18%). One was stomatitis and another was uncontrolled ascites in an advanced cirrhotic pt. The response rate in the 9 evaluable pts was 67% with 6 PR and no CR. The duration of the response was 5 to 9 months. One- and two-year survival rates were 75% and 22%, respectively. These results were superior to those of the intermittent bolus injection of 5-FU plus MMC (or epirubicin) in 40 pts from 1977 to 1994. These results suggest that continuous 5-FU plus LV arterial infusion is an effective regimen in pts with liver metastases from colorectal cancer. However, the infusion with an extracorporeal device limits the pts' quality of life. Further investigation is needed for a schedule that can be practiced for a longer period.
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PMID:[Continuous intraarterial infusion of 5-fluorouracil plus leucovorin for liver metastases from colorectal cancer]. 785 96

In an ongoing prospective study 11 patients with unresectable liver metastases from colorectal carcinoma have been treated with hepatic-arterial infusion of 5-FU (1 g m-2) for 24 h on days 1 to 5 combined with a rapid infusion of high-dose leucovorin (100 mg m-2) (HD-regimen) or low-dose leucovorin (20 mg m-2) (LD-regimen) on days 1, 3 and 5. There was only mild local toxicity grade 1 and grade 2 in both regimen. Twenty-four cycles with high-dose leucovorin and 42 cycles with low-dose leucovorin showed a mild to moderate systemic toxicity, including haematological changes, stomatitis and diarrhoea. We did not see any grade 4 toxicity and no treatment-related fatalities occurred in this series. Eighty per cent reduction of leucovorin dosage leads to a significant decrease in grade 2 and grade 3 haematological and gastrointestinal toxicity.
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PMID:Local and systemic toxicity of intra-hepatic-arterial 5-FU and high-dose or low-dose leucovorin for liver metastases of colorectal cancer. 818 66

Due to the pattern of tumor infiltration, hepatic resection may be accomplished in 20% of all patients with colorectal liver metastases. However, a new recurrence is observed very often and early. Up to date, systemic adjuvant treatment failed to improve the overall results. Taking into account the benefit of palliative intrahepatic chemotherapy, intraarterial therapy was performed as an adjuvant to removal of metastatic colorectal liver metastases in 51 out of 90 patients over an eight year period (1982-90). Due to abnormal arterial liver arteries 5 pat. got an intraportal catheter. The following monthly treatment schedules were applied: FUDR (fluorodesoxyuridine) 0.2-0.3 mg/kg/d/14 d (N = 12), FUDR 1,2 mg/kg/d/5d (N = 21), FUDR 1.0-1.7 mg/kg/d/5 and folinic acid 30 mg/m2/d (N = 18). Mortality (5.5%) and morbidity (36%) were not increased by catheter implantation. Local and systemic side effects were mainly stomatitis 0-22% and hepatobiliary toxicity 6-42%. Including an operative mortality of 5.5%, the median survival of 45 months was associated with a disease-free interval of 15 months. Intrahepatic recurrence was diagnosed after a median time of 26 months (extrahepatic recurrence was 25 months respectively). The following prognostic factors were associated with favourable survival: solitary metastasis (p > 0.001), curative resection, segmentectomy, normal serum levels of CA 19-9 and LDH. Although both groups were not comparable, due to more extended tumor infiltration in the treatment group (p = 0.03), adjuvant arterial chemotherapy delayed after curative resection intrahepatic recurrence to 52 versus 14 months (p = 0.036). Disease-free survival was improved to 19 versus 12 months (p = 0.08) resulting in a trend to better overall survival (p = 0.07).
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PMID:[Adjuvant regional chemotherapy after resection of liver metastases of primary colorectal tumors]. 832 38

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

The pharmacokinetics of docetaxel as investigated in Phase I and Phase II trials are discussed. Phase I trials have shown that docetaxel exhibits linear pharmacokinetics consistent with a three-compartment model. Population pharmacokinetic and pharmacodynamic analysis of the results of 22 nonrandomized Phase II trials with nonlinear mixed-effects modeling showed that the interpatient variability of docetaxel pharmacokinetics is mainly related to body surface area and hepatic function. The effect of body surface area on clearance does not present a problem, since the dose of docetaxel is adjusted for body size. However, patients with impaired liver function are at increased risk of serious adverse effects (febrile neutropenia, severe infections, severe stomatitis, and toxic death) during treatment with docetaxel 100 mg/ m2. Patients with impaired liver function should receive a reduced dose (75 mg/m2). The presence of liver metastases without impaired liver function had no effect on docetaxel's clearance or safety, suggesting that a dose of 100 mg/m2 is well tolerated in such patients. Docetaxel pharmacokinetics and pharmacodynamics determined in Phase I and Phase II trials indicate a need to adjust the dosage for body surface area and liver function.
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PMID:Pharmacokinetic and pharmacodynamic properties of docetaxel: results of phase I and phase II trials. 943 28

A 37-year-old man was diagnosed as having a rectal cancer with familial adenomatous polyposis, with the mutation of APC gene, and gastric polyposis, hypertrophy of the retinal pigment epithelium and a lipoma of the left arm. The patient underwent a total colectomy for the rectal cancer and a partial resection of the liver for metastasis (S3) which was detected on laparotomy, followed by cannulation in the hepatic artery. After the operation, 5-FU alone and low doses of CDDP and 5-FU were administered, but the level of serum CEA elevated and CT scanning showed multiple liver metastases. Then, low doses of leucovorin (30 mg/body bolus) and 5-FU (500 mg/body/h) were injected through an injection port every week. After 6 months, the level of serum CEA reduced and CT scanning showed minor response (about 30% on the decrease rate), without side effects, including diarrhea, stomatitis and bone marrow suppression.
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PMID:[A case of hepatic metastasis of rectal cancer with familial adenomatous polyposis treated by transarterial administration of low-dose leucovorin and 5-FU]. 949 38

High-dose chemotherapy combining regional hepatic artery infusion (HAI) of fluorodeoxyuridine (HAI FUDR) and systemic venous infusion of 5-fluorouracil (i.v. 5-FU) was delivered against liver metastases from colorectal cancer. The hypothesis that chronomodulation of delivery rate along the 24 h time scale would improve the tolerable doses of both drugs was tested. Combined HAI FUDR (80 mg/m2/day) and i.v. 5-FU (1200 mg/m2/day) were administered for five consecutive days every 3 weeks, either as a constant rate infusion (schedule A, 27 patients) or as chronotherapy (schedule B, 29 patients). This latter regimen consisted of a sinusoidal modulation of the delivery rate over the 24 h scale with a maximum at 16:00 for FUDR and 4:00 for 5-FU. Intrapatient dose escalation up to the individual maximum tolerated doses (MTD) was planned for both drugs in the absence of any previous grade 3 or 4 toxicity. All patients had metastatic colorectal cancer, with adjuvant or palliative chemotherapy given to six patients (22%) on schedule A and 12 patients on schedule B (41%). Severe stomatitis occurred in 71% of the patients and was dose limiting. No hepatic toxicity was encountered. Dose reductions of 5-FU and/or FUDR were required for 17 of 27 patients on schedule A (63%) as compared to 11 of 29 patients on schedule B (38%), following reaching the individual MTD (p<0.05). Over the first six cycles, patients on schedule B received higher doses (mg/m2/cycle; FUDR: 522 +/- 85 versus 499 +/- 50, p=0.004 and 5-FU: 5393 +/- 962 versus 5136 +/- 963, p=0.009) and higher dose intensities (mg/m2/week; FUDR: 164 +/- 46 versus 151 +/- 52, p=0.018 and 5-FU: 1652 +/- 478 versus 1553 +/- 535, p<0.041) of both drugs than patients on schedule A. As a result the number of courses with doses of 5-FU above 1200 mg/m2/day and/or FUDR above 110 mg/m2/day was larger in group B than in group A (5-FU, A: 67 of 268, 25% versus B: 133 of 321, 41% and FUDR, A: 86 of 268, 32% versus B: 155 of 321, 48%; p<0.001). Objective responses were observed in 13 patients on schedule A (48%) and 11 patients on schedule B (38%). The results support the need for further exploration of chronotherapy of colorectal cancer liver metastases with combined arterial and venous fluoropyrimidine chemotherapy.
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PMID:Continuous delivery of venous 5-fluorouracil and arterial 5-fluorodeoxyuridine for hepatic metastases from colorectal cancer: feasibility and tolerance in a randomized phase II trial comparing flat versus chronomodulated infusion. 1037 73

Raltitrexed (Tomudex), a novel folate-based inhibitor of thymidylate synthase, has demonstrated anti-tumour efficacy comparable with 5-fluorouracil and leucovorin in patients with advanced colorectal cancer (CRC). This phase II study was conducted to evaluate the anti-timor efficacy and tolerability of raltitrexed in patients with advanced CRC who had received one previous chemotherapy regimen. Raltitrexed was administered at a dose of 3.0 mg/m2 i.v. over 15 min once every 3 weeks. Of 43 eligible patients, 53% had colon cancer and 47% rectal cancer. Objective responses were observed in 16% of patients [95% confidence interval (CI): 7-31%; seven partial responses). The median duration of response was 101 days (range: 45-239 days), the median overall duration of response was 145 days (range: 104-302 days) and the median survival was 11.6 months (95% CI: 9.4-14.7 months). Liver metastases showed a 17% (three of 18) response rate and lung metastases a 12% (three of 25) response rate. Adverse events of grade 3 or 4 reported for more than 5% of patients were neutropenia (23%), leukopenia (9%), reversible SGPT increase (7%) nausea/vomiting (19%), anorexia (14%), asthenia (9%) and hypotension (7%). Grade 3 or 4 diarrhea, stomatitis and alopecia were not observed. In summary, raltitrexed had an acceptable toxicity profile and promising anti-tumor activity against advanced CRC in patients who had received prior chemotherapy. Further clinical trials of combination chemotherapy using raltitrexed are warranted.
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PMID:Phase II study of raltitrexed (Tomudex) in chemotherapy-pretreated patients with advanced colorectal cancer. Tomudex Cooperative Study Group. 1057 7

We present the case of a 72-year-old man with gastric tube cancer accompanied by multiple liver metastases, after esophagectomy for esophageal cancer, whose quality of life (QOL) was improved with a small dosage of TS-1. The patient's high serum AFP level suggested alpha-fetoprotein-producing gastric cancer. He was treated with half the standard dose of TS-1, because the patient's poor general condition necessitated chemotherapy with low toxicity and high efficacy. The daily dose was 40 mg for the first three courses and 50 mg for the last two. Each treatment course consisted of a four-week administration followed by two drug-free weeks. The patient received five courses of chemotherapy at our outpatient clinic before his death from re-progression of liver metastasis. No serious side effect except temporary stomatitis was observed. A decrease in tumor markers, alpha-fetoprotein and carcinoembryonic antigen, was obtained after 4 weeks. After 2 cycles, computed tomography and endoscopy examinations showed regression of the primary tumor and liver metastases, and tumor markers were decreased remarkably. The patient's QOL improved gradually after the treatment. His performance status before the chemotherapy was 3, and improved to 1 after two cycles. The small dosage of TS-1 was effective without any adverse effects, and improved the patient's QOL, for 6 months.
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PMID:[A patient with advanced gastric cancer in the gastric tube whose QOL was improved by TS-1]. 1191 37


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