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)

Locally advanced or metastatic adenocarcinoma of the stomach still carries a poor prognosis, with 5-year survival rates of < 15%. Palliative chemotherapeutic regimens for this disease are largely 5-FU-based. We have investigated the clinical activity of an oral combination of uracil and tegafur (UFT) with calcium folinate (Orzel), in patients with measurable metastatic disease. Thirty-six patients received a total of 94 courses of daily UFT 300 mg/m2 plus calcium folinate 90 mg for 28 consecutive days followed by a 7-day rest. Planned treatment doses were maintained in 83% of all evaluable courses. Main toxicities included diarrhea (21 patients) and nausea and vomiting (20 patients). Other side effects were asthenia, malaise, stomatitis, and myelosuppression. At present, 26 patients are evaluable for response. Of these, one achieved a complete response and three achieved partial remissions. In addition, six patients reached stable disease, yielding an overall response rate of 27%. We conclude that the combination of UFT and calcium folinate is a feasible outpatient regimen that warrants further clinical evaluation.
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PMID:UFT and oral calcium folinate as first-line chemotherapy for metastatic gastric cancer. 1044 64

This study was designed to evaluate the activity, safety and tolerance of docetaxel (D) in a selected population with metastatic squamous cell carcinoma of the head and neck (SCCHN). Twenty-four patients with no prior palliative therapy were enrolled and received D 100 mg m(-2) by 1 h of infusion, every 3 weeks. All but two patients had been evaluated for efficacy on lung metastatic sites. No prophylactic administration of anti-emetics or growth factors was given. A pharmacokinetic study was performed in 22 patients. Twenty-one patients were assessable for response and 24 for toxicity. One hundred and four cycles were administered with a median of 4.5 (range 1-9) per patient. The median cumulative dose was 449 mg m(-2). Partial responses were achieved in five patients with a median duration of 18.7 weeks (range 13.1-50.3). The overall response rate was 20.8% with a median duration of 11.0 weeks (range 2.4-52.6). The most frequent side-effect was neutropenia (79.2% grade IV) but with a short duration (median 4 days) and no febrile neutropenia. The incidence of moderate/severe fluid retention was 29.2% with one treatment discontinuation. Other toxicities (all grades) were common (skin 75%, asthenia 50%, infection 29.2%, nausea 16.7%, diarrhoea 12.5%, stomatitis 16.7%, vomiting 8.3% and HSR 8.3%). A mean clearance of 19.6 l h(-1) m(-2) and an area under the curve of 6.00 microg ml(-1) h(-1) was found in the pharmacokinetic analysis. Docetaxel is active in this selected population with metastatic SCCHN, with a good tolerance.
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PMID:A phase II study of docetaxel in patients with metastatic squamous cell carcinoma of the head and neck. 1050 70

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

Melatonin (MLT) has been proven to counteract chemotherapy toxicity, by acting as an anti-oxidant agent, and to promote apoptosis of cancer cells, so enhancing chemotherapy cytotoxicity. The aim of this study was to evaluate the effects of concomitant MLT administration on toxicity and efficacy of several chemotherapeutic combinations in advanced cancer patients with poor clinical status. The study included 250 metastatic solid tumour patients (lung cancer, 104; breast cancer, 77; gastrointestinal tract neoplasms, 42; head and neck cancers, 27), who were randomized to receive MLT (20 mg/day orally every day) plus chemotherapy, or chemotherapy alone. Chemotherapy consisted of cisplatin (CDDP) plus etoposide or gemcitabine alone for lung cancer, doxorubicin alone, mitoxantrone alone or paclitaxel alone for breast cancer, 5-FU plus folinic acid for gastro-intestinal tumours and 5-FU plus CDDP for head and neck cancers. The 1-year survival rate and the objective tumour regression rate were significantly higher in patients concomitantly treated with MLT than in those who received chemotherapy (CT) alone (tumour response rate: 42/124 CT + MLT versus 19/126 CT only, P < 0.001; 1-year survival: 63/124 CT + MLT versus 29/126 CT only, P < 0.001). Moreover, the concomitant administration of MLT significantly reduced the frequency of thrombocytopenia, neurotoxicity, cardiotoxicity, stomatitis and asthenia. This study indicates that the pineal hormone MLT may enhance the efficacy of chemotherapy and reduce its toxicity, at least in advanced cancer patients of poor clinical status.
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PMID:Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. 1067 14

Marshall's syndrome or periodic fever syndrome was first described in 1987 in the USA based on observations of 12 children under the age of five with periodic fever (> 38 degrees C) and accompanying aphtous stomatitis, pharyngitis, and cervical adenopathy (PFAPA). In 1998, a national retrospective study was carried out in France by the pediatric infectious pathology group, and a semeiological analysis was made of 22 cases. The main characteristics of Marshall's syndrome found in this patient population were in agreement with those reported in the literature. The onset of symptoms occurred between the age of 3 months and 12 years, with a mean age of 5 years; no geographical or ethnic predisposing factors were noted. The diagnosis of symptoms was subsequently established at an age ranging from 5 months to 16 years, with a mean age of 6.5 years. It was determined that following an initial phase of generalized clinical manifestations (asthenia, cranial neuritis, dysphagia, anorexia), the symptoms become stereotyped, with the sudden appearance of high fever (> 40 degrees C), shivering, aphtous stomatitis, pharyngitis, and cervical adenopathy. Other symptoms such as cranial neuritis, arthralgia, and abdominal pain may also be present (50% of cases in the present study), but due to their variability of appearance they are of lesser diagnostic value. The main characteristic of Marshall's syndrome is its periodic aspect; with fever occurring every 6 to 9 weeks, with a mean interval of 66 days before recurrence of fever compared to the shorter interval of 21 to 28 days reported in the literature. After excluding the presence of an infection, the differential diagnosis includes the following: familial Mediterranean fever, hyper IgD syndrome, and feverish neutropenia. During the periods of fever, an inflammatory syndrome with hyperleucocytosis and a marked increase in C-reactive protein (CRP) levels and sedimentation rate is observed. The most effective treatment seems to be the early administration of corticoids during the initial phase, prior to the appearance of more specific symptoms. The prognosis is excellent, with a progressive decrease in the incidence of periodic fever and an absence of complications. However, the etiology of Marshall's syndrome has not yet been determined.
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PMID:[Marshall syndrome: results of a retrospective national survey]. 1094 83

The aim of the study was to define a regular and tolerable dose of the epirubicin-docetaxel combination in first-line chemotherapy of patients with metastatic breast cancer. Sixty-five women with measurable and/or evaluable disease were treated with epirubicin escalated from 60 to 110 mg/m(2) according to 5 dose levels, in combination with a fixed dose of 75 mg/m(2) docetaxel, every 21 days for 6 cycles, without preventive use of hematopoietic growth factors or antibiotics. Forty-three women received adjuvant chemotherapy, consisting of anthracyline- or anthracenedione-based regimens in 39 cases (60%). Twenty-seven women were treated in the phase I study (3 at epirubicin 60 mg/m(2), and 6 at each subsequent dose level). Dose-limiting toxicity consisted of grade III asthenia and febrile neutropenia (epirubicin 75 mg/m(2)), grade IV thrombopenia and grade III asthenia (epirubicin 90 mg/m(2)), grade IV stomatitis and grade III diarrhea (epirubicin 100 mg/m(2)), and grade III diarrhea (epirubicin 110 mg/m(2)). In the phase II study, an additional 38 women were treated at epirubicin 90 mg/m(2) and epirubicin 100 mg/m(2). During the 349 cycles delivered, grade IV neutropenia occurred in 90%; febrile neutropenia requiring hospitalization occurred in 62 (17.8%) and lasted more than 3 days in 12 (3.4%). Nonhematologic toxicity was acceptable. Three left ventricular ejection fraction depressions occurred and normalized during follow-up. The overall response rate in the 62 evaluable women was 69.4% (range: 58--81%), with a median duration of 7.8 months. After 26 months of follow-up, the median time to progression was 9.1 months and median overall survival was 22.7 months. On the basis of efficacy and toxicity, the recommended dose of the combination is epirubicin 100 mg/m(2) plus docetaxel 75 mg/m(2).
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PMID:Epirubicin--docetaxel combination in first-line chemotherapy for patients with metastatic breast cancer: final results of a dose-finding and efficacy study. 1147 55

Polyethylene glycol-coated (pegylated) liposomal doxorubicin (PLD) is a new formulation of doxorubicin with peculiar pharmacokinetic and pharmacodinamic properties, a favorable toxic profile and a demonstrated activity in solid tumors. We tested PLD in locally advanced or metastatic NSCLC patients, progressed after a platinum-based first-line chemotherapy. PLD was administered at the dose of 35 mg/m(2) every 21 days. After the first six patients had been accrued, due to the low toxicity shown in the first six patients, the dose was escalated to 45 mg/m(2). Seventeen patients were enrolled in the study and were considered eligible for evaluation of toxicity and response. Stomatitis, palmar-plantar erythrodysaesthesia (PPE) and asthenia were the most common toxicities and affected approximately half of the treated patients. Stomatitis occurred in 8/17 patients and was grade 3-4 in three. PPE was seen in 9/17 and was grade 3 in one. In the group treated at the dose of 45 mg/m(2) PPE was more frequent and severe and required treatment delay in some cases. Other toxicities were equally distributed among the two groups. Hematological toxicity was not common and never reached grade 3-4. However, one patient with grade 2 leucopenia had pneumonia and died. Clinically evident heart failure was never recorded. Left ventricular ejection fraction was assessed in three patients after PLD treatment (in one case after the first course, due to the occurrence of atrial fibrillation, and in two cases after six courses) and was unchanged compared to pre-treatment assessment. One confirmed partial response was observed (5.8%); five patients (29.4%) had stable disease (including one minor response) and nine (52.9%) had disease progression. Median time to progression was 9.5 weeks, median survival 18.6 weeks. PLD at the doses employed in this study can be safely administered and has shown activity in platinum pretreated NSCLC patients.
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PMID:Single-agent pegylated liposomal doxorubicin (Caelix) in chemotherapy pretreated non-small cell lung cancer patients: a pilot trial. 1175 Jul 14

Melatonin (MLT) is the main hormone released from the pineal gland and has proved to have physiological antitumor activity. MLT has been shown to exert anticancer activity through several biological mechanisms: antiproliferative action, stimulation of anticancer immunity, modulation of oncogene expression, and anti-inflammatory, anti-oxidant and anti-angiogenic effects. Several experimental studies have shown that MLT may inhibit cancer cell growth, and preliminary clinical studies seem to confirm its anticancer property in humans. In addition, MLT may have other biological effects, which could be useful in the palliative therapy of cancer, namely anticachectic, anti-asthenic and thrombopoietic activities. On this basis, the present clinical investigation was performed in an attempt at better definition of the therapeutic properties of MLT in human neoplasms. In a first clinical study, we evaluated the effects of MLT in a group of 1,440 patients with untreatable advanced solid tumors, who received supportive care alone or supportive care plus MLT. In a second study, we evaluated the influence of MLT on the efficacy and toxicity of chemotherapy in a group of 200 metastatic patients with chemotherapy-resistant tumor histotype, who were randomized to receive chemotherapy alone or chemotherapy plus MLT. In both studies, MLT was given orally at 20 mg/day during the dark period of the day. The frequency of cachexia, asthenia, thrombocytopenia and lymphocytopenia was significantly lower in patients treated with MLT than in those who received supportive care alone. Moreover, the percentage of patients with disease stabilization and the percentage 1-year survival were both significantly higher in patients concomitantly treated with MLT than in those treated with supportive care alone. The objective tumor response rate was significantly higher in patients treated with chemotherapy plus MLT than in those treated with chemotherapy alone. Moreover, MLT induced a significant decline in the frequency of chemotherapy-induced asthenia, thrombocytopenia, stomatitis, cardiotoxicity and neurotoxicity. These clinical results demonstrate that the pineal hormone MLT may be successfully administered in medical oncology in the supportive care of untreatable advanced cancer patients and for the prevention of chemotherapy-induced toxicity.
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PMID:Is there a role for melatonin in supportive care? 1186 1

Tegafur is a prodrug of the antineoplastic agent fluorouracil, and is administered in a 1:4 molar ratio with the fluorouracil modulator uracil. Oral tegafur/uracil 300 mg/m(2)/day plus calcium folinate 75 or 90 mg/day for 28 days every 35 days was as effective as intravenous (IV) fluorouracil 425 mg/m(2)/day plus folinic acid 20 mg/m(2)/day for 5 days every 28 or 35 days in the treatment of patients with metastatic colorectal cancer in two large, randomised, nonblind, multicentre trials (n = 816 and 380). Median survival time among patients treated with tegafur/ uracil or fluorouracil was approximately 12 months in both trials. Results from both trials also demonstrated no significant between-group differences in overall response rates among patients treated with oral tegafur/uracil (12 and 11%) or IV fluorouracil (15 and 9%). In elderly patients (aged > or = 70 years) with metastatic colorectal cancer, results from small noncomparative studies showed that treatment with oral tegafur/uracil afforded overall response rates of 12.5 to 29% and was well tolerated. During preoperative treatment with oral tegafur/uracil plus calcium folinate as an adjunct to radiotherapy in patients with stage II or III rectal cancer, the maximum tolerated dosage of tegafur/uracil was 350 mg/m(2)/day (administered 5 days per week for 5 weeks). Among the 15 patients who were followed for 5 to 8 months, three had a complete response to treatment. Treatment with tegafur/uracil was also given postoperatively. The most common adverse events associated with oral tegafur/uracil were anaemia, nausea/vomiting, diarrhoea, thrombocytopenia, mucositis, neutropenia, asthenia, anorexia and abdominal pain. Oral tegafur/uracil was associated with a significantly more favourable tolerability profile than IV fluorouracil in the two large randomised trials. In particular, stomatitis and most adverse haematological events were less frequent.
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PMID:Oral tegafur/uracil. 1188 48

Based on the synergistic cytotoxicity demonstrated in vitro by topoisomerase I inhibitors followed by docetaxel and the feasibility of giving both drugs on a weekly schedule avoiding overlapping toxicities, we designed a phase I trial of weekly CPT-11 (irinotecan)/docetaxel to determine the dose-limiting toxicities (DLT) and the maximum-tolerated dose (MTD) of this combination. Eighteen patients with advanced solid tumors treated with at least one prior chemotherapy regimen were included in this trial. CPT-11 was administered as a 90-min (intravenous) IV infusion followed immediately by docetaxel as a 30-min IV infusion. Both drugs were given on days 1, 8 and 15 in 4-week cycles. Four escalating dose levels of CPT-11/docetaxel (level I: 60/20 mg/m(2), level II: 60/25 mg/m(2), level III: 70/25 mg/m(2), and level IV: 70/30 mg/m(2)) were studied. Forty-seven cycles were administered (range, 1-5 courses) with a median number of 2.6 cycles per patient. Grade 4 leukopenia was the DLT reached at dose-level IV (CPT-11/docetaxel 70/30 mg/m(2)). Four patients had grade 3 anemia at dose levels III (two patients) and IV (two patients), while grade 3/4 thrombocytopenia was not seen. Grade 3/4 non-hematologic toxicities included grade 3 diarrhea in two patients (dose levels II and IV), grade 3 asthenia in one patient (dose level II) and grade 3 stomatitis in one patient (dose level I). The recommended dose of this weekly schedule is CPT-11 70 mg/m(2) and docetaxel 25 mg/m(2). DLT of this regimen is leukopenia, although toxicity is manageable at the recommended dose level. The activity of this regimen is being evaluated in a phase II study in previously treated patients with advanced non-small cell lung cancer.
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PMID:Phase I study of weekly CPT-11 (irinotecan)/docetaxel in patients with advanced solid tumors. 1214 Jan 45


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