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)

Twenty-six adult patients were entered in a phase I trial of carboplatin, a new cisplatin derivative with reduced potential for nephrotoxicity. All patients had solid tumors and the median World Health Organization performance score was 2 (0-3). Twelve patients had not received prior chemotherapy. The drug was administered as a 15-minute IV infusion, without pre- or posthydration, at daily doses of 40-125 mg/m2 for five consecutive days. Antiemetics were given only if needed. Thrombocytopenia and neutropenia were dose related and dose limiting. One patient died from septic shock at the highest dose level. Nonhemolytic anemia was also encountered. Nausea and vomiting were experienced by most patients but gastrointestinal intolerance was severe in only two patients. One patient had hypercreatininemia, which was minor and rapidly reversible. Other toxic effects consisted of negligible fatigue, paresthesia, pruritus, local pain, stomatitis, headache, and alopecia. Although none of the patients achieved a partial or complete response, antitumor effect was strongly suggested in two patients with thyroid and cervix cancer, respectively. Carboplatin is an attractive candidate for phase II trials. In good-risk patients, such trials could be initiated at a daily dose of 100 mg/m2 for five consecutive days every five to six weeks.
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PMID:Phase I study of carboplatin given on a five-day intravenous schedule. 636 28

HexMF consists of hexamethylmelamine 150 mg/m2 D2-15, mitomycin C (MMC) 10 mg/m2 D2 and 5-fluorouracil (5-FU) 30 mg/kg/day as a continuous infusion D1-5 in 4-5 week cycles. It was designed as an alternative to treating patients with standard single agents in sequence, thereby preventing the testing of new drugs as part of primary therapy. Median survival was 12+ months for patients with measurable and 18+ months for patients with nonmeasurable colorectal cancer. It was 9+ months from the onset of secondary chemotherapy. Toxicity included severe thrombocytopenia (50%), severe leukopenia (25%), and moderate stomatitis (50%). Only one instance of leukopenia was life-threatening. The MMC and 5-FU infusion skeleton provides an attractive strategy for testing new drugs as primary therapy. HexMF itself has a potentially broad antitumor spectrum and excellent acceptance by patients. It is suitable for additional phase II trials.
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PMID:Phase II trial of combination chemotherapy of colonic cancer with 5-fluorouracil, mitomycin C, and hexamethylmelamine. 640 37

The response rate of metastatic colorectal carcinoma confined to the liver to HAI of FUDR alone is at the range of 50% and to mitomycin C by hepatic arterial infusion (HAI) at the range of 35%. Mitomycin C was added to FUDR by continuous infusion and given by HAI to 12 patients with colorectal cancer confined to the liver. Catheters were placed subselectively in the hepatic artery, and infusion continued for five to six days when the catheter was removed. Cycles were repeated every 30 days. Chemotherapy consisted of mitomycin C 15 mg/m2 administered on day 1 followed by FUDR 100 mg/m2 by continuous infusion daily for five days. Response to treatment was evaluated by serial determinations of plasma CEA and by imaging techniques consisting of a computerized tomography, sonography, and radionuclide scanning of liver as well as by angiography. In 2 patients, complete remission was achieved; in 4 patients a 75% and in another 4 patients a 50% decrease in liver metastasis was observed, while 2 patients had stable disease. Thus, a response rate of 83% with a median duration of six to seven months was achieved. The median survival of the these patients was 16 months. Eight of the 12 patients have failed previous, i.v. 5-FU containing regimens. Complications related to 45 treatment cycles were the following: catheter displacement in 11.1%, an intimal tear, usually in the hepatic artery in 4.4%, gastric ulcerations in 5.4%, and septicemia in 2.7% of the cycles. In addition, aneurysmal dilation of the hepatic artery occurred in 4 patients (8.8% of the treatment cycles), all of whom continued treatment. Chemotherapy-related complications included primarily thrombocytopenia and stomatitis. Mitomycin C + FUDR by hepatic arterial infusion is an effective treatment for colorectal carcinoma metastatic to the liver. The high response rate justifies the adjuvant treatment of Dukes class C colon cancer patients with this treatment.
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PMID:Percutaneous hepatic arterial infusion (HAI) of mitomycin C and floxuridine (FUDR): an effective treatment for metastatic colorectal carcinoma in the liver. 644 76

A phase I-II study of KW2083, an analog of mitomycin C (MMC) was performed in a total of 22 patients. KW2083 was escalated by single intravenous administration of 40, 50, 60, 70, and 80 mg/m2 doses. Treatments were repeated every 4-6 weeks unless unacceptable toxicities occurred. The median times taken to reach nadir for each dose level were 9-12 days for leukocytes and 7-13 days for platelets respectively. The median times taken for recovery were 8-22 days for leukopenia and 10-37 days for thrombocytopenia. Variable and non-predictable hematological toxicity was observed in some cases. Biphasic hematological toxicity was observed in 4 courses. Acute toxicity occurred in 17 courses for 11 patients and consisted of nausea (44%), vomiting (13%), diarrhea (2.7%) and stomatitis (2.7%). Nephrotoxicity (elevation of BUN, 8.1% and proteinuria, 5.4%) occurred in 3 patients who had no previous impairment of renal function. Alopecia (8.1%) was also observed. Marked elevations of hepatic enzymes were noted in one patient who developed acute fulminant hepatitis with the second dose of KW2083. Objective response was observed in one of 20 evaluable patients. From this preliminary study, the maximum tolerable dose is 70 mg/m2 and the optimal dose of KW2083 was determined to be 50 mg/m2 at 6-week intervals. KW2083 has been introduced as an MMC analog of potential interest. However, hematological and non of hematological toxicities are very similar to those of MMC and does not appear that KW2083 will supersede MMC.
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PMID:[Phase I-II study of 7-N-(P-hydroxyphenyl)-mitomycin C (KW2083, M83)]. 647 44

A phase II study of KW 2083 [7-N-(p-Hydroxyphenyl)-Mitomycin C] was carried out in 14 cases of stomach cancer, 5 of lung cancer, 5 of colon cancer and 5 other types of cancer. KW 2083 was intravenously injected at a dose of 40 mg/body weekly in 26 cases. Among 23 evaluable cases, partial response was obtained in 6 cases (26%). The PR cases were 4 of stomach cancer and 2 of lung cancer, the former being all undifferentiated adenocarcinoma. Regarding hematologic toxicities, thrombocytopenia was the most principal toxicity and an important weak point of KW 2083. Thrombocytopenia (less than 75,000/mm3) was observed in 13 cases (50%). Recovery took about 4 weeks, but by that time 3 cases had still not recovered to 75,000/mm3. leukocytopenia (less than 3,000/mm3) was observed in 17 cases (65%). Concerning gastrointestinal symptoms, anorexia occurred in 11 cases (42%), nausea and vomiting in 11 cases (42%), diarrhea in 1 case and stomatitis in 1 case. T1/2 (beta-phase) of KW 2083 was half that of Mitomycin C.
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PMID:[Phase II study of KW 2083 [7-N-(p-hydroxyphenyl)-mitomycin C] in patients with various cancers]. 650 15

Thirty patients with advanced head and neck cancer of diverse histologies received the combination of cis-diamminedichloroplatinum (CDDP) (100 mg/m2) and 5-fluorouracil (5-FU) (1,000 mg/m2/24 hours X 4 days) at 3-4 week intervals. Among all study participants, the median time to progression was 3.9 months and the median survival was 7.2 months. Among 20 patients with squamous cell carcinoma, we observed five objective regressions (25%). None of the responders had prior chemotherapy; four had extensive prior radiation therapy. Among 10 patients with non-squamous cell carcinoma neoplasms, we detected three objective responses (30%). Histopathology of the responding patients included poorly differentiated sarcoma, anaplastic carcinoma, and malignant mixed parotid tumor. Significant gastrointestinal toxicities included moderate-to-severe nausea (60%), vomiting (43%), and stomatitis (57%). Leukopenia (less than 4,000 cells/mm3) and thrombocytopenia (less than 130,000 cells/mm3) affected 78% and 41% of patients, respectively, without sepsis or hemorrhage.
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PMID:A phase II study of cis-diamminedichloroplatinum and 5-fluorouracil in advanced upper aerodigestive neoplasms. 654 Jul 63

Seventy-two patients with neoplastic disease in a variety of anatomic sites were treated with sequential methotrexate (MTX) and 5-fluorouracil (5-FU) followed by leucovorin (LV) rescue. Treatment consisted of MTX, 160 mg/m2 as a 10-min infusion; 5-FU, 600 mg/m2 as a bolus 90 min later; and LV, a minimum of 25 mg/m2 or 15 mg/m2 p.o. q.6h. X 4, repeated at 1- or 2-wk intervals. Responses of any type included 4 of 24 colon cancers, 3 of 12 stomach cancers, 0 of 6 pancreas cancers, 1 of 2 gallbladder cancers, 4 of 6 breast cancers, 1 of 1 uterus cancer, 2 of 2 selected lung cancers, 1 of 1 parotid cancer, 1 of 2 sarcomas, and 0 of 6 ovary cancers. Response appeared to increase survival. The best-quality responses were observed in patients with stomach, breast, and parotid tumors. Toxicities included anemia requiring transfusion (20%), anorexia during treatment with LV (16%), moderate thrombocytopenia (12%), grade 3 stomatitis (12%), moderate granulocytopenia (10%), severe conjunctivitis (6%), severe gastroenteritis (6%), vomiting (6%), anamnestic reactions (6%), possible renal failure (4%), and possible pulmonary failure (2%). One patient had life-threatening gastroenteritis and reappearance of a grade 1 to 2 skin reaction of the entire treatment field more than 5 yr after radiotherapy. Patients with prior cis-platin therapy had a 50% risk of life-threatening pancytopenia. The results encourage controlled primary trials testing intensification of the sequential combinations with parallel investigations of MTX alone with and without diminished doses of LV.
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PMID:MTX/5-FU trials in gastrointestinal and other cancers. 660 24

Four separate groups of patients have been studied: (1) The effect of high-dose methotrexate (MTX) administration on glomerular filtration rate was determined by pre- and posttreatment inulin and creatinine clearances in nine patients. Measurements were made prior to and 24-40 hr after drug administration. Inulin and creatinine clearances both decreased a mean of 43%. No signs of systemic toxicity occurred. (2) Three other patients given high-dose courses of MTX developed MTX toxicity. Their creatinine clearance decreased an average of 61%. (3) In a separate group of five patients undergoing weekly MTX treatment, comparison of serum MTX pharmacokinetics with and without alkalinization of the urine demonstrated no significant difference in peak serum MTX levels or serum MTX decay. (4) Eight additional patients with severe renal dysfunction secondary to MTX were treated with increased doses of leucovorin and a continuous infusion of thymidine (8 g/m2/day) once renal failure was recognized. When high-dose leucovorin and thymidine were begun 48-72 hr after the MTX infusion, severe toxicity in the form of leukopenia, thrombocytopenia, diffuse mucositis, stomatitis, or skin rash was averted. We concluded the following: (1) high-dose MTX causes a subclinical decrease in glomerular filtration rate with each administration, even in nontoxic courses; (2) alkalinization of the urine with sodium bicarbonate does not alter plasma MTX decay, while volume expansion (hydration) is maintained constant; and (3) rigorous monitoring of serum creatinine and serum MTX levels 24-48 hr after MTX administration allows for the institution of rescue measures, including leucovorin and thymidine, which will abort the systemic toxicity that accompanies MTX-induced renal failure.
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PMID:Methotrexate-induced renal impairment: clinical studies and rescue from systemic toxicity with high-dose leucovorin and thymidine. 660 76

5-FU, semustine (MeCCNU), triazinate (TZT), and razoxane (ICRF-159) have each shown activity against advanced colorectal cancer in studies by at least two investigative groups. Objective response rates, however, have been low, without evidence of increased patient survival. The hope of this study was that enhanced activity might result from giving these agents in two-drug combinations. There were 167 eligible and evaluable patients randomized among the programs: 5-FU at a dose of 500 mg/m2/day by iv push X 5 (F); 5-FU at a dose of 400 mg/m2/day iv X 5 plus TZT at a dose of 175 mg/m2/day iv X 3 (FT); 5-FU at a dose of 400 mg/m2/day plus ICRF-159 at a dose of 600 mg/m2/day orally X 3 (FI); MeCCNU at a dose of 150 mg/m2/day orally plus TZT at a dose of 200 mg/m2/day iv X 3 (MT); MeCCNU at a dose of 150 mg/m2 orally plus ICRF-159 at a dose of 500 mg/m2/day orally X 3 (MI); and ICRF-159 at a dose of 425 mg/m2/day orally X 3 plus TZT at a dose of 125 mg/m2/day iv X 3 (IT). Patients with limiting conditions (serum creatinine greater than 1.5 mg/dl or elevated bilirubin) were randomized among programs F, FI, and MI. Objective response rates by treatment arm were: F--13% (four of 31 patients); FT--13% (four of 31); FI--15% (four of 27); MT--11% (three of 28); MI--13% (four of 32); and IT--6% (one of 17). Response rates of combination arms were not significantly larger than those of 5-FU alone. With regard to survival, patients initially treated with 5-FU alone had the most favorable experience (median, 10.8 mos). Multivariate analysis showed the following factors to have a significant and independent influence on survival: Eastern Cooperative Oncology Group performance score, grade, site of indicator lesion, and the presence of 5-FU in the treatment regimen. Toxic effects most frequently seen were nausea, vomiting, thrombocytopenia, leukopenia, diarrhea, stomatitis, alopecia, and dermatitis. The incidence and severity of toxicity were roughly comparable among the six treatment arms.
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PMID:Randomized phase II studies in advanced colorectal carcinoma: a North Central Cancer Treatment Group study. 664 May 51

A boy born healthy, developed gastrointestinal symptoms (diarrhea, vomiting, ulcerative stomatitis) and megaloblastic anaemia with thrombocytopenia and neutropenia at the age of five weeks. Serum levels of folate and cobalamin were normal, but there was cobalamin-mal absorption. In his serum apo-TC2 was not detectable and immunoreactive total TC2 was very low (10% of normal values). Cultured skin fibroblasts failed to secrete functioning TC2. Pharmacological amounts of parenteral Cyanocobalamin, administered regularly, led to hematological remission and normal development. Interruption of therapy was followed by relapse within a few weeks. A coexisting hypogammaglobulinemia did not respond to cobalamin therapy at the selected dose level. A family investigation of serum TC2 concentrations and the genetic TC2 variants in 7 persons of three generations yielded evidence of autosomal-recessive inheritance of a silent TC2 allele (TC2 QLFL SEA-like). Three persons with heterozygous deficiency were asymptomatic.
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PMID:[Inherited transcobalamin-II-deficiency: clinical, genetic studies and diagnosis using cultured fibroblasts]. 666 2


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