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)

5-Fluorouracil (5-FU) and bleomycin (BLM) are active agents in head and neck squamous-cell cancer (H-N-scc). Less toxicity and an enhanced activity have been reported when these agents are administered by continuous infusion (CI), with or without a bolus of cisplatin (CDDP), another active agent. Thirty-three patients with recurrent and/or metastatic head and neck squamous cell carcinoma were treated with a combination regimen including CDDP (100 mg/m2) on day 1 plus BLM (15-mg bolus followed by 16 mg/m2/day by CI) and 5-FU (650 mg/m2/day by CI) on days 1-5 every 3 weeks. Thirty-one patients were evaluable for toxicity and response. The response rate (RR) was 15% (5 of 31), with one complete response (CR) and four partial responses (PRs), at a confidence interval of 95% (0-34%). Four of the five responders had not received previous radiotherapeutic treatment. Toxicity was deemed acceptable; nausea and vomiting and stomatitis were moderate. Only one patient had irreversible renal toxicity, after two cycles of chemotherapy. No symptomatic lung toxicity was observed. Good antitumour activity was noted for previously untreated disease (3 of 4; 75% RR). This combination of drugs proved to be inactive, however, in previously irradiated recurrent and/or metastatic H-N-scc (1 of 25; 4% RR). These results underscore the need to be extremely attentive to different patient populations when selecting therapeutic schedules and when analyzing reported results.
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PMID:Phase II study of cisplatin and continuous-infusion 5-fluorouracil and bleomycin for recurrent and metastatic head and neck squamous-cell carcinoma. 169 3

Tumor necrosis factor-alpha (TNF-alpha) has a spectrum of biologic effects and has been shown to exert antiviral effects in fibroblasts in vitro. The in vivo administration of TNF-alpha (40-160 micrograms/m2 intravenously over 2 hr) and its effects on vesicular stomatitis virus (VSV) replication in peripheral blood mononuclear cells (PBMC) from patients with malignancy was investigated. Blood was obtained before, during, and after infusion. The PBMC were separated and infected with VSV at a multiplicity of infection of 0.005 plaque-forming units/cell and virus yields were determined 72 h later. The TNF-alpha inhibited VSV yields by as much as 99% in a dose-dependent manner with the inhibition initially observed during the first hour of infusion. Despite a rapid reduction in TNF-alpha serum levels, the higher doses still produced antiviral effects 4 hr after the infusion. Sera obtained at identical times had no interferon activity. Human gamma-interferon (25 micrograms/ml) added in vitro augmented the TNF-alpha-induced inhibitory activity in both magnitude and duration. Percentages of lymphocytes and monocytes in peripheral blood were reduced at 4 hr after TNF-alpha administration and the monocyte to lymphocyte ratio was diminished and temporally coincided with the loss of TNF-induced antiviral state. These data suggest that the in vivo administration of TNF has a direct inhibitory activity on VSV replication in human peripheral blood mononuclear cells that was enhanceable by gamma-interferon and possibly monocyte mediated.
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PMID:In vivo administration of tumor necrosis factor-alpha is associated with antiviral activity in human peripheral mononuclear cells. 170 3

Mitoxantrone is a dihydroxyanthracenedione derivative which as intravenous mono- and combination therapy has demonstrated therapeutic efficacy similar to that of standard induction and salvage treatment regimens in advanced breast cancer, non-Hodgkin's lymphoma, acute nonlymphoblastic leukaemia and chronic myelogenous leukaemia in blast crisis; it appears to be an effective alternative to the anthracycline component of standard treatment regimens in these indications. Mitoxantrone is also effective as a component of predominantly palliative treatment regimens for hepatic and advanced ovarian carcinoma. Limited studies suggest useful therapeutic activity in multiple myeloma and acute lymphoblastic leukaemia. Regional therapy of malignant effusions, hepatic and ovarian carcinomas has also been very effective, with a reduction in systemic adverse effects. Mitoxantrone inhibits DNA synthesis by intercalating DNA, inducing DNA strand breaks, and causing DNA aggregation and compaction, and delays cell cycle progression, particularly in late S phase. In vitro antitumour activity is concentration- and exposure time-proportional, and synergy with other antineoplastic drugs has been demonstrated in murine tumour models. Leucopenia may be dose-limiting in patients with solid tumours, whereas stomatitis may be dose-limiting in patients with leukaemia. Other adverse effects are usually of mild or moderate severity although cardiac effects, particularly congestive heart failure, may be of concern, especially in patients with a history of anthracycline therapy, mediastinal irradiation or cardiovascular disease. Mitoxantrone displays an improved tolerability profile compared with doxorubicin and other anthracyclines, although myelosuppression may occur more frequently. Thus, mitoxantrone is an effective and better tolerated alternative to the anthracyclines in most haematological malignancies, in breast cancer and in advanced hepatic or ovarian carcinoma. Further studies may consolidate its role in the treatment of these and other malignancies.
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PMID:Mitoxantrone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the chemotherapy of cancer. 171 46

Twenty-eight patients with refractory advanced malignancies were treated with a 24 hr infusion of 5-fluorouracil (5-FU), Leucovorin (LV), and N-(phosphonacetyl)-L-aspartic acid (PALA) weekly. Twenty-seven patients were evaluable for the assessment of toxicity and anti-tumor activity. PALA was administered as intravenous bolus over 15 min at a fixed dose, 250 mg/m2 24 hr before the start of 5-FU and LV infusions. 5-FU was initially administered at 750 mg/m2 and was incrementally increased to 2600 mg/m2. LV was administered in a fixed dose of 500 mg/m2 concurrently with 5-FU over a 24-hr period. The course was repeated weekly. Diarrhea, stomatitis, nausea, and vomiting were among dose-limiting toxic effects. Other toxicities observed were hand-foot syndrome, hair loss of scalp/eyelashes, overall weakness, rhinitis, and chemical conjunctivitis. Maximum tolerated dose (MTD) of 5-FU in this combination and schedule was 2600 mg/m2. Seven of 14 patients treated at 2600 mg/m2 were able to tolerate the chemotherapy on a weekly basis without interruption. The other seven patients required dose de-escalation, a majority of whom contained 5-FU at a dose of 2100 mg/m2. Twenty-three of 27 patients had been previously treated. Eight patients achieved a partial response, all of whom were previously treated, except three patients. A complete response was observed in a patient with pancreatic carcinoma, previously untreated. Overall response rate for the patients who were treated at the 5-FU dose of 2100 mg/m2 or 2600 mg/m2 is 9 of 18 patients (50%).
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PMID:Phase I study of high dose 5-fluorouracil and high dose Leucovorin with low dose phosphonacetyl-L-aspartic acid in patients with advanced malignancies. 173 89

Oral complications commonly affect cancer patients undergoing active treatment. These include oral infection, gingival bleeding, stomatitis/mucositis, xerostomia, dental caries and periodontal disease. The oral cavity also acts as an entry site for systemic infection, particularly in those who are myelosuppressed. This paper reviews the structure and function of the oral cavity and how this may be affected by anticancer therapy. Oral care procedures are discussed and controversial areas highlighted showing that, although it is generally agreed that oral care is essential in preventing/minimizing complications and maintaining general comfort, there is no general agreement about the frequency with which care is required or about the tools and agents to be employed. Areas for future research are highlighted.
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PMID:The oral complications of specific anticancer therapy. 176 79

Patients undergoing chemotherapy or radiotherapy for malignancies often develop annoying inflammation of the oral mucosa as a side-effect of cytotoxic therapy. As prostaglandins are known to be cytoprotective Prostin E2 was given to 10 patients with neoplasms of the ear, nose, pharynx or larynx, or of the maxillofacial region, who received radiotherapy. The reference group was made up of five patients with the analogous diagnosis who received the conventional therapy with Hexoral sol. One patient was not administered any therapy. The patients that were given Prostin E2 did not develop either the inflammatory process or stomatitis. In the reference group the inflammatory process appeared in two patients and lesions were noticed in one patient. Excellent results, although still preliminary, pointed out that preventive local administration of Prostin E2 was superior to the conventional therapy and that accordingly, Prostin E2 should be regarded as the drug of choice.
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PMID:[Use of prostin E2 in the treatment of stomatitis caused by radiotherapy]. 182 22

35 evaluable patients were treated with 5'-deoxy-5-fluorouridine (doxifluridine), a fluoropyrimidine derivative. All patients had been heavily pretreated and had refractory disease. Treatment with doxifluridine at a dosage of 3000 mg/m2 given intravenously for 5 successive days at 3-week intervals led to 6 partial remissions (17%). The main side-effects were central neurotoxicity, stomatitis and myelotoxicity, resulting in 2 toxic deaths. In patients with renal function disturbances, toxicity proved to be more severe. We concluded that the drug should not be used in patients with renal impairment. Because responses have been encountered, further evaluation of the drug may be warranted in the less toxic oral form.
Eur J Cancer 1991
PMID:Phase II clinical trial of doxifluridine in patients with advanced ovarian cancer. 182 17

Since continuous exposure increases the cytotoxicity of 5-Fluorouracil, this agent is now commonly administered by 4-5 day continuous infusions. However Phase I studies have suggested that infusion of doses up to 450 mg/m2/day for at least 28 days may be possible. In the present study 12 patients with advanced head and neck cancer were treated with continuous infusion 5-Fluorouracil at starting doses of 400-450 mg/m2/day for 28 days followed by a 14 day rest period. Patients received a median of 2.5 cycles over 10 weeks for a median total 5-Fluorouracil dose of 12,700 mg/m2. One patient achieved Partial Response. Significant stomatitis (Grade II or greater) was seen more frequently than predicted from Phase I studies (8/12 patients) and was the most common cause for dose reduction. Diarrhea, emesis, palmar/plantar syndrome and skin rash were also noted. No significant myelosuppression was seen. Extremely large amounts of 5-Fluorouracil can be delivered to head and neck cancer patients by extended infusion. However due to the high frequency of stomatitis in this population, lower starting doses than those used in this study may be required.
Sel Cancer Ther 1991
PMID:Tolerance of extended (28 day) continuous infusion of 5-fluorouracil in advanced head and neck cancer. 183 3

The mouth and throat are vulnerable sites in cancer patients, subject to treatment-related stomatitis and mucositis, and infection due to bacteria, viruses, and fungi. The author presents a summary of the conditions and their causes, and an update on current treatments of choice.
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PMID:Prevention and treatment of oral complications in the cancer patient. 183 77

36 patients with advanced malignancy were studied in a phase I trial of continuous 24-h infusion of floxuridine (FUdR) plus etoposide plus cisplatin (FEP) administered for 5 consecutive days at 4-week intervals. Study design fixed the dose rate of etoposide and cisplatin with escalation of FUdR only. Dose rate-limiting toxicity related to the FUdR component was stomatitis and diarrhoea and was invariably associated with leukopenia and thrombocytopenia when grade 3 or 4 level gastrointestinal toxicity was observed. Only 3 of 64 courses were associated with transient renal failure related to cisplatin. Drug-related deaths occurred (leukopenia-associated sepsis) in 4 patients with poor performance status (ECOG 3 and 4). Responses occurred in 15 of 26 evaluable patients (all previously treated minimally or untreated) including 5/11 non-small cell lung cancer; 3/3 oesophageal; 2/2 breast; 4/5 gastric; 1 osteogenic sarcoma; and 1 unknown primary (probably ovary). The recommended dose rates for a 5-day infusion of the three agents for good risk patients is 20 mg/m2 per day of each drug. For poor risk patients including age greater than 65 years; performance status 2 or greater; or extensive bone metastases or prior radiation; the recommended starting dose rates are: FUdR 15 mg/m2 per day; etoposide 15 mg/m2 per day; and cisplatin 20 mg/m2 per day. Dose escalation of FUdR to a maximum of 25 mg/m2 daily is feasible in selected patients demonstrating optimal tolerance.
Eur J Cancer 1991
PMID:Infusion of floxuridine plus etoposide plus cisplatin in human malignancies. 183 61


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