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)

Auranofin (triethylphosphine gold), an oral gold preparation, has recently been made available, and along with injectable gold preparations, is of therapeutic value for rheumatoid arthritis. Serious gold toxicity is uncommon, and drug-related deaths rare. Many potential adverse reactions are similar, including dermatitis, stomatitis, thrombocytopenia, leucopenia, and proteinuria, generally with increased incidence in the injectable gold-treated patients. Oral gold is associated with benign lower gastrointestinal side effects, including diarrhoea, loose stools and abdominal cramps that are often dose-related and resolve spontaneously. The incidence of severe reactions such as thrombocytopenia, aplastic anaemia and exfoliative dermatitis is lower with oral gold than injectable preparations, and contributes to a superior risk-benefit ratio. The treatment of gold toxicity depends on the type and extent of organ involvement.
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PMID:Adverse reactions with oral and parenteral gold preparations. 329 22

The combination of cis-platinum and 5-fluorouracil has been reported to act synergistically with improved response rates in squamous cell carcinomas of the head and neck. The activity of bolus cis-platinum and continuous infusion of 5-fluorouracil in 24 patients with recurrent and metastatic squamous cell carcinoma of the cervix was evaluated. Twelve patients were stage I, 3 were stage II, 5 were stage III, and 4 were stage IV cervical carcinomas. Among the 24 patients, there were 4 complete and 8 partial responses (50%). The overall median response was 24 weeks. The overall cumulative survival was 55% at 40 weeks and 40% at 1 year after beginning this regimen. Complications included 4 patients who developed leukopenia, 3 thrombocytopenia, 11 stomatitis, 14 nephrotoxicity, 4 peripheral neuropathy, and 6 ototoxicity. The combination of cis-platinum and continuous infusion of 5-fluorouracil appears to have useful activity in patients with recurrent or metastatic squamous cell carcinoma of the cervix.
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PMID:Evaluation of bolus cis-platinum and continuous 5-fluorouracil infusion for metastatic and recurrent squamous cell carcinoma of the cervix. 333 66

A phase II clinical trial of epirubicin, a new anthracycline anticancer antibiotic, was carried out in 41 patients with inoperable or recurrent gastric cancer. Epirubicin was administered by i.v. injection; the dosages were either 40-60 mg/m2 every three weeks (Regimen A) or 20-30 mg/m2/day for 3 days every three weeks (Regimen B). Twenty-one patients were entered into Regimen A, and 20 into Regimen B. Of 31 evaluable patients, 16% (5/31) experienced objective response (PR); i.e., 20% (three of 15) treated with Regimen A and 13% (two of 16) with Regimen B, showing that there was no significant difference in the rate of response between the two regimens. Adverse effects observed were relatively mild in most cases and included anemia, leukopenia, thrombocytopenia, anorexia, nausea/vomiting, diarrhea, stomatitis and alopecia. Tachycardia and extrasystole were observed in 3 cases but disappeared upon discontinuation of the treatment. In conclusion, epirubicin seemed to have therapeutic activity comparable to that of doxorubicin in gastric cancer while being less toxic than doxorubicin, and is expected to become a better alternative to the latter drug.
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PMID:[Phase II study of epirubicin in inoperable or recurrent gastric cancer]. 345 31

A phase II study of epirubicin, a new anthracycline derivative, was performed in 23 patients with advanced gastric cancer. Epirubicin was administered intravenously at a dose of 20-30 mg/m2/day for two or three consecutive days every two or three weeks. Sixteen cases were evaluable and there were two partial responses and one minor response. Overall response rate (more than PR) was 12.5% (2/16). Leukopenia (less than 4,000/mm3) and anemia (less than 11.0 g/dl) were observed in 71.4% and 69.2% of patients, respectively. No thrombocytopenia was observed. Other toxicities were alopecia (71.4%), nausea and vomiting (42.9%), anorexia (25.0%), stomatitis (12.5%), fatigue (12.5%), fever (6.3%) and tachycardia (6.3%), but these effects were relatively mild in most cases.
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PMID:[Phase II study of epirubicin on gastric cancer--a cooperative study of the Tokai Cancer Chemotherapy Group]. 346 May 30

Colon carcinoma, the second leading cause of cancer-related deaths in the United States, is resistant to chemotherapy in a large majority of cases. Single-agent and combination chemotherapy have failed to prolong survival. New approaches are clearly needed. In experimental models, a steep dose-response curve for colorectal cancer has been demonstrated using various agents. The hematopoietic toxicity of high-dose therapy with these drugs can be circumvented by autologous bone marrow transplantation. We investigated the use of high-dose melphalan with autologous bone marrow rescue in 20 patients with metastatic colon carcinoma. Each patient received melphalan, 180 mg/m2 intravenously (IV), followed eight hours later by bone marrow infusion. Median duration of granulocytopenia (less than 500 neutrophils/microL) was twelve days (range, 5 to 35 days), while transfusion-dependent thrombocytopenia (less than 20,000 platelets/microL) had a median duration of eight days (range, 3 to 23 days). Time to bone marrow engraftment was not affected by prior 5-fluorouracil therapy. Nausea and vomiting occurred in 14 patients but was generally short lived. Mild stomatitis, esophagitis, and diarrhea were common. Severe gastrointestinal (GI) side effects did not occur. One treatment-related death occurred secondary to intramural tumor necrosis, which resulted in massive lower GI bleeding. Complete responses were observed in three patients (15%) and partial responses in six patients (30%), for an overall response rate of 45%. Median survival was 198 days in this group of patients with extensive disease. High-dose melphalan therapy for metastatic colon carcinoma, when used with autologous bone marrow transplantation, appears to achieve a high response rate with tolerable toxicity. Further investigation is needed to define the role of this therapy in the care of advanced colon carcinoma.
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PMID:Phase II trial of high-dose melphalan and autologous bone marrow transplantation for metastatic colon carcinoma. 353 54

Twenty-nine patients with recurrent or advanced, incurable head and neck cancer were entered into a phase I-II trial of carboplatin in combination with 5-fluorouracil (5-FU), 1,000 mg/m2/d continuous intravenous (IV) infusion for five days every 28 days. The initial dose of carboplatin was 300 mg/m2 for patients with Karnofsky performance scores greater than or equal to 70%, and 240 mg/m2 for patients with scores of 50% to 60%. Subsequent doses were modified to achieve grade 2 myelo-suppression: WBC, 2,000 to 2,999 cells/microL; granulocytes, 1,000 to 1,499 cells/microL; and platelets, 50,000 to 75,000 cells/microL. Dose levels were 180, 240, 300, 360, and 420 mg/m2. Twenty-eight patients had squamous-cell cancers and one had an adenoid cystic carcinoma of the parotid. There were 26 patients with recurrent disease; 22 had received prior RT; only two had received other chemotherapy immediately before study entry. Three patients had newly diagnosed incurable stage IV disease. The median performance status was 80% (range, 60% to 90%). All patients had objectively measurable disease, and 28 were evaluable for response. There were three complete responses (CRs) and ten partial responses (PRs) (48% CR and PR); the median duration of response was 4.7 months (range, 1.5 to 15+ months). Dose-limiting toxicities were granulocytopenia, thrombocytopenia, and stomatitis. Prolonged myelosuppression delayed retreatment in eight patients and delayed 19 of 107 (18%) courses. Stomatitis occurred in 61% and diarrhea in 29%. 5-FU dosage was decreased in ten patients (36%) for grade 2 or greater stomatitis or diarrhea. Mild to moderate nausea and vomiting occurred in 66% of patient trials in which no pretreatment antiemetics were administered. Other toxicities included phlebitis from 5-FU in 71%, skin toxicity in 11%, mild alopecia in 25%, and fatigue in 54% of patients. Nephrotoxicity (creatinine greater than 2.0 mg/dL) occurred in one patient. The dose of carboplatin resulting in grade 2 toxicity was 180 mg/m2 in one patient, 240 mg/m2 in one, 300 mg/m2 in seven, 360 mg/m2 in ten, and 420 mg/m2 in one. Based on these results, we recommend a starting dose of carboplatin, 300 mg/m2, in combination with five days of continuous infusion 5-FU. In this dose and schedule, this combination was well tolerated and demonstrated antitumor activity in head and neck cancer. To confirm these promising results, a Southwest Oncology Group prospective randomized trial is in progress comparing carboplatin and 5-FU, cisplatin and 5-FU, and standard-dose weekly methotrexate in recurrent-disease patients.
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PMID:A phase I-II trial of carboplatin and 5-fluorouracil combination chemotherapy in advanced carcinoma of the head and neck. 354 42

The therapeutic effect of low-dose MTX-treatment (10-25 mg/week) in active rheumatoid arthritis can be demonstrated by an improvement in clinical and laboratory parameters of disease activity already after 4-6 weeks. The mode of action is not fully understood. Direct anti-inflammatory effects seem to be more important than the weak immunosuppressive properties. Methotrexate treatment is indicated in all very active cases of rheumatoid arthritis, which do not respond to, or do not tolerate, conventional slow-acting antirheumatic drugs. In severe, rapidly progressing diseases MTX can be given without waiting for the effect of other disease modifying drugs. MTX is administered once a week i.v., i.m. or in one oral dose before breakfast. Absorption is reduced by food. The initial weekly dose is 15-25 mg and can be reduced to a minimum of 10 mg (7.5 mg) according to the clinical effect. A combination with antimalarials or gold salts is possible. The prescription of MTX is contraindicated in cases of renal function disturbances, active liver disease, bone marrow disturbances, active infectious diseases, pregnancy and excessive alcohol consumption. The most common side-effects are nausea and vomiting, stomatitis, transient elevations of transaminases. Rare conditions are leucopenia, thrombocytopenia and lung infiltrations. The side-effects are dose-related and disappear with dose reduction. They can be avoided by administering leucovorin 12 hours after giving MTX. Before starting the treatment total blood count with differential count and platelet count, serum creatinine and liver enzymes should be done. These laboratory studies have to be repeated every week for the first month, every two weeks up to the third month and every 1-2 months thereafter. When contraindications are considered and regular controls are made methotrexate is better tolerated than other cytotoxic agents. The rate of withdrawals is lower than with gold-treatment. In low-dose MTX-treatment drug interactions do not play a major role with normal renal function. Concomitant application of nonsteroidal antirheumatic drugs can delay MTX elimination and increase toxicity. We therefore avoid giving these drugs on the day of MTX-administration as far as possible.
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PMID:[Treatment with low-dose methotrexate in chronic polyarthritis. Review of the literature]. 354 54

We conducted parallel phase II trials of cimetidine as a single agent and the combination N-phosphonacetyl-L-aspartate (PALA) plus L-alanosine among 40 previously untreated patients with biopsy-proven, measurable disseminated malignant melanoma. We did not design the trial to be a comparative assessment of the two regimens. Among 19 patients treated with cimetidine, 300 mg orally four times daily, there was one complete response of extensive pleural and pulmonary metastases for 16+ months and two partial regressions of soft tissue lesions for 7 and 21+ months, respectively. Among 21 patients treated with the combination regimen, there was only one partial response in soft tissue for 1 month. The median times to progression and death were 1.4 and 6 months, respectively, for cimetidine, and 1.3 and 4 months, respectively, from the combination of PALA plus L-alanosine. Among patients who progressed on initial treatment, there were no responses in 12 who received crossover therapy with cimetidine and 11 with the combination regimen. Two patients treated with the combination program had severe stomatitis, two developed renal failure, and one had severe leukopenia and thrombocytopenia. Recognizing the limitations of small sample size, these early observations suggest that cimetidine may have intriguing implications in the management of disseminated malignant melanoma.
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PMID:Phase II studies of single-agent cimetidine and the combination N-phosphonacetyl-L-aspartate (NSC-224131) plus L-alanosine (NSC-153353) in advanced malignant melanoma. 359 11

Tricyclic nucleoside phosphate (TCN-P) was selected for clinical trials because of its unusual chemical structure and activity against L1210 murine leukemia and MX-1 mammary xenograft. Inhibiting DNA synthesis, TCN-P was more toxic during S-phase of cell cycle. A phase I study was conducted in 24 patients with advanced solid cancers. The drug was given as a slow i.v. injection over 5 min on Days 1, 8, 15, and 22 of a 42-day cycle with a 2-week rest. Five dose levels ranging from 12 to 96 mg/m2 were studied with 3 to 12 patients treated at each level; a total of 106 doses was administered. The major hematological toxicity was thrombocytopenia, with a median nadir occurring at Day 34 of the cycle and first appearing at doses greater than 24 mg/m2. Anemia was seen at each dose level occurring between Days 8 and 34. Non-myelosuppressive toxic effects included stomatitis, anorexia, transient fever, nausea and vomiting, and dose-limiting hyperglycemia and diarrhea. The highest tolerated dose was 48 mg/m2. Plasma, pleural fluid, urine, and tissue samples were analyzed for TCN-P and tricyclic nucleoside (TCN) in selected patients by high-performance liquid chromatography. Plasma decay curves revealed extended retention of both TCN and TCN-P. Autopsy specimens obtained 61 days after therapy showed the highest residues of TCN-P in liver metastases and of TCN in gall bladder, bile, and pancreas. No drug was detected in urine samples of two patients. Prolonged retention and erratic plasma levels of the drug are probably due to extensive enterohepatic circulation, as well as repeated interconversion between TCN-P and TCN within cells. This weekly schedule produced unexpected clinical toxicity and should not be pursued.
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PMID:Phase I evaluation and clinical pharmacology of tricyclic nucleoside 5'-phosphate using a weekly intravenous regimen. 369 29

Twenty-two patients with advanced adenocarcinoma of the lung were treated with the combination chemotherapy "EACAM" consisting of cyclophosphamide (333mg/m2 X 1), adriamycin (27mg/m2 X 1), cisplatin (25mg X 5), nimustine (33mg/m2 X 1), and methotrexate (27mg/m2 X 3). This regimen was repeated once every 4 or 5 weeks. One complete response (CR) and 8 partial responses (PR) were obtained in 21 evaluable patients and the response rate was 42.9%. It has not been possible to calculate the median survival time for all of the evaluable cases, since 13 of them are still alive up to the present time. The side effects observes were as follows: nausea and vomiting (81.8%), alopecia (81.8%), stomatitis (22.7%), leukocytopenia less than 2,000/mm3 (45.5%), and thrombocytopenia less than 5 X 10(4)/mm3 (18.2%). Apart from strong myelosuppression, no severe infection or bleeding tendency was noticed. A mild elevation of serum createnine was observed in one patient, and no patients developed renal insufficiency. The combination chemotherapy "EACAM" is therefore considered to be a very effective and tolerable treatment for adenocarcinoma of the lung.
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PMID:[Combination chemotherapy with cyclophosphamide, adriamycin, cisplatin, nimustine(ACNU), and methotrexate (EACAM) in advanced adenocarcinoma of the lung]. 385 52


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