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)

An important subset of malignancies arising in the ovary or digestive organs remains confined to the peritoneal cavity throughout its natural course. These tumors constitute appropriate targets for loco-regional therapy. With this rationale a clinical phase I and pharmacokinetic study of intraperitoneally administered N, N', N'' triethylenethiophosphoramide (thiotepa), an alkylating agent with activity against ovarian carcinoma, was initiated with the objectives of determining the systemic and local toxicities, maximum-tolerated dose, and pharmacokinetic advantage associated with using the drug in this manner. A total of 13 patients received 15 courses of intraperitoneal thiotepa at doses ranging from 30 mg/m2 to 60 mg/m2. The only important systemic toxicity observed was myelosuppression. At 50 mg/m2 two patients developed Eastern Cooperative Oncology Group (ECOG) grade III myelosuppression. At 60 mg/m2, the maximum-tolerated dose, the mean nadir WBC and platelet counts were 2.7 X 10(3)/microliter and 110 X 10(3)/microliter, respectively. There were no instances of vomiting, stomatitis, or alopecia. Pharmacokinetic studies performed in nine patients revealed that thiotepa was rapidly lost from the peritoneal cavity in a biexponential fashion with a mean t1/2 alpha of 0.26 +/- 0.08 hour and a mean t1/2 beta of 2.13 +/- 0.52 hour. Concomitant with the rapid loss of drug from the peritoneal cavity was the rapid rise in drug levels in the plasma, with peak plasma values approaching those associated with intravenous administration. Peritoneal exposure to thiotepa expressed as the area under the curve (AUC)peritoneal fluid was 7 to 34 micrograms/mL X hour. Systemic exposure expressed as the AUCplasma ranged between 0.95 and 7.71 micrograms/mL X hour. The observed pharmacokinetic advantage of intraperitoneal administration calculated as AUCperitoneal fluid/AUCplasma was 4.3 +/- 0.6. This relatively small advantage, combined with our observation of rapid appearance of the active metabolite, tepa, into the plasma argue against an important role for intraperitoneal administration of thiotepa.
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PMID:Phase I clinical and pharmacokinetic study of thiotepa administered intraperitoneally in patients with advanced malignancies. 249 84

Ninety-two nonsmall cell lung cancer (NSCLC) patients were treated with a combination chemotherapy containing methotrexate, adriamycin, cyclophosphamide and CCNU (MACC). The regimen was administered in the dose and schedule originally reported. Median survival for all patients was 32 weeks. Only 6 patients demonstrated an objective response with a median survival rate of 51 weeks. The remaining 70 evaluable patients were nonresponders. These latter patients had a survival probability reduced to 29 weeks. Median time to progression for the whole group was 17 weeks. Partial responses were seen in 3 squamous, 1 large cell carcinoma and 1 adenocarcinoma. One patient with bronchiolo-alveolar carcinoma had complete disease regression and is still alive 136 weeks after starting treatment. Toxicity was significant with 2 treatment-related deaths. The major toxic effects consisted of myelosuppression, nausea, vomiting, and stomatitis. Alopecia was nearly universal; a mild cardiac, renal, or hepatic toxicity was relatively infrequent. Polychemotherapy with MACC regimen may benefit a few selected patients with NSCLC, but its overall antitumor efficacy appears to be very limited.
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PMID:Combination chemotherapy with methotrexate, adriamycin, cyclophosphamide and CCNU (MACC) for nonsmall cell lung cancer. 4-year experience with 92 patients. 254 37

Three hundred five patients with advanced pancreatic and gastric carcinoma were randomly assigned to treatment with fluorouracil, fluorouracil plus doxorubicin (Adriamycin) (FA), or fluorouracil plus doxorubicin plus mitomycin (mitomycin C) (FAM). All regimens were equivalent with regard to patient survival. There is no reasonable likelihood that either the FA or FAM regimen could produce a meaningful survival advantage over fluorouracil alone. Interval to disease progression, objective response rates, and palliative effects (improved performance, body weight, or symptoms) were essentially equivalent among the three regimens. With regard to toxicity, the FAM regimen produced more anorexia, nausea, vomiting, leukopenia, thrombocytopenia, and cumulative bone marrow suppression. Fluorouracil alone produced more stomatitis and diarrhea. Because of a failure to produce improved survival or palliation, unrewarded toxicity, and excessive cost, neither the FA nor FAM regimen can be recommended for the treatment of advanced pancreatic or gastric cancer.
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PMID:A comparison of three chemotherapeutic regimens in the treatment of advanced pancreatic and gastric carcinoma. Fluorouracil vs fluorouracil and doxorubicin vs fluorouracil, doxorubicin, and mitomycin. 257 57

Twenty-eight adult patients with primary refractory or relapsed acute leukemia were treated. The regimens consisted of mitoxantrone plus cytosine arabinoside for 17 patients with acute non-lymphocytic leukemia (ANLL) and mitoxantrone accompanied with vincristine and prednisolone for 11 patients with acute lymphoblastic leukemia (ALL). In primary refractory patients, 1 of the 4 (25%) ANLL and 1 of the 3 (33%) ALL attained complete remission (CR). Excluding 2 patients who underwent bone marrow transplantation, 8 of the 13 (62%) relapsed ANLL and 4 of the 8 (50%) relapsed ALL achieved CR with a median duration of remission of 6.2 months and 3.8 months, respectively. Myelosuppression occurred in all treatment courses and was associated with pyrexia due to infections in 84% of the cases. Nausea, vomiting and stomatitis were mild. Abnormal liver function tests were observed in 8 (28%) patients. One patient, pretreated with 550 mg/m2 of doxorubicin, developed congestive heart failure. The results suggest that mitoxantrone is of value in the treatment of Chinese patients with refractory or relapsed acute leukemia.
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PMID:Treatment of refractory or relapsed adult acute leukemia by using mitoxantrone-containing regimens. 263 48

Eighty patients with advanced gastrointestinal tumors (64% with colorectal cancer) entered a phase III prospective randomized study with 5-fluorouracil (5-FU) vs 5-FU + folinic acid (FA) The treatment included 5-FU, 600 mg/m2/week for 6 weeks, given as i.v. bolus alone (arm A), or administered by rapid injection half-way through a one-hour infusion of FA, 200 mg/m2/week for 6 weeks (arm B). Partial remission (PR) was achieved in 1 out of 30 (3%) evaluable patients for 6 months in arm A, and in 10 out of 34 (29%) patients in arm B, with a median duration of 8 months (range 6-17) (comparison of the response rate: P = 0.005). In patients with colorectal cancer the response rate was 5% and 27% in arm A and in arm B respectively (P = 0.06). Two patients, who were resistant to 5-FU alone, achieved PR after treatment with 5-FU + FA. Diarrhea was observed in 14/42 patients (33%) in arm B (grade 1-2 in 10 and grade 3 in 4) and in 2/38 patients (5%) in arm A (P = 0.005). Other side effects such as nausea/vomiting, myelosuppression and stomatitis were infrequent and of mild intensity in both arms. No statistical difference in survival was detected when comparing the two groups (estimated median survival 8 months and 11 months for arm A and arm B respectively). These results seem to indicate that the weekly regimen of 5-FU + FA has a superior response rate compared to 5-FU alone, and that it is well tolerated. However, the advantage is not reflected in overall survival.
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PMID:A randomized clinical trial with a weekly regimen of 5-fluorouracil with or without folinic acid in advanced gastrointestinal adenocarcinomas: a preliminary report. 267 60

Fifty-two non-resectable and recurrent cancer patients with prior treatment, were entered in this study; 1 esophageal, 33 gastric, 1 duodenal, 4 colorectal, 2 pancreatic, 2 bile duct, and 9 breast cancer. The protocol of this therapy was as follows: On day 1, 500 mg/body cyclophosphamide (CPM) was administered by drip infusion, and on day 2, 200 mg/m2 methotrexate (MTX) was infused intravenously for 30 min; immediately after, 500 mg/body 5-fluorouracil (5-FU) was injected by bolus infusion for 5-10 min. On day 3, 24 hours after MTX administration, leucovorin rescue was added. This combination chemotherapy was repeated every two weeks. As a result, 35 of 52 patients were evaluable and the response rate (CR + PR) was investigated; 2/21 (9.5%) for gastric, 2/7 (28.6%) for breast, and 0% for miscellaneous. As complications for side effect, general fatigue, anorexia, nausea, vomiting and stomatitis were observed symptomatically, and leukopenia and thrombocytopenia were recognized in laboratory data as dose limiting factors.
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PMID:[Combination chemotherapy of CPM-MTX-5-FU in non-resectable and recurrent cancer patients]. 271 79

Two trials of leucovorin (LV) and 5-fluorouracil (5-FU) in patients with metastatic colorectal cancer were done, both using a 3-day loading dose and then weekly doses to minimize toxicity. The first trial used LV administered by intravenous infusion with a constant dose of 5-FU 400 mg/m2, and the second trail used oral LV with increasing doses of 5-FU. In the first trail, 45 eligible patients (20 with and 25 without previous therapy) were treated. Toxicity usually consisted of diarrhea or weakness and was controlled by delaying or decreasing the 5-FU dose. Subjective responses occurred in 75% of patients but did not correlate with antineoplastic effect. Objective responses were seen in 36% and stabilization of disease in 31% of patients; these correlated with prolonged survival. Median survival was 8 months for patients with previous treatment and 10 for those without. Twelve-month survival was 32% and 40%, respectively. There was no correlation between the development of toxicity and response or survival. The second trial was conducted recently in cooperation with Duke University to determine toxicity and efficacy of oral LV with intravenous 5-FU before a randomized trial of this combination versus placebo with intravenous 5-FU. Eighteen patients were treated, and serum levels of folates were obtained on ten. First toxicity occurred at 5-FU doses ranging from 375 to 850 mg/m2, and consisted of diarrhea in nine, lethargy in seven, nausea/vomiting in four, dermatitis in four, conjunctivitis in two, hypersalivation in two, stomatitis in one, and profound granulocytopenia in one. Response rate was 35%, and stabilization was 35% with median survival of 14 months. Twelve-month survival was 56%.
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PMID:Clinical experience with leucovorin and 5-fluorouracil. 278 80

Nineteen patients with biopsy-proven high-grade astrocytomas received as initial treatment whole-brain radiation and combination chemotherapy with 5-fluorouracil (5-FU), 1,000 mg/m2/24 h as a continuous infusion for 96 h, and bolus cisdiamminedichloroplatinum II (CDDP), 100 mg/m2. Chemotherapy cycles were repeated on day 21, then every 28 days until progression or completion of six cycles. All 19 patients completed one cycle of chemotherapy. Toxicity was moderate, with cytopenias, nausea, vomiting, diarrhea, stomatitis, and reversible azotemia. Survival ranged from 2 to 160+ weeks, with a median of 35 weeks. The survival of the pilot group was compared with historical controls treated with radiation plus 1,3,-bis(2-chloroethyl)-1-nitrosourea (BCNU). Controls were similar in histology, age, performance score, and survival, without statistically significant differences. The combination of radiation therapy, continuous-infusion 5-FU, and bolus CDDP as described here for high-grade astrocytomas is moderately toxic and appears to offer no survival advantage compared with radiation therapy plus BCNU.
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PMID:Pilot study of combination 5-fluorouracil, cisdiamminedichloroplatinum II, and radiation therapy for grade III and IV astrocytomas. 282 91

Taxol is a plant product derived from the western yew, Taxus brevifolia. We have conducted a phase I clinical study of Taxol used intravenously daily for 5 days at 3-week intervals. The starting dose was 5 mg/m2 daily, and the highest dose used was 40 mg/m2 daily for 5 days. The daily dosage of Taxol was mixed in 250 mL of intravenous fluid and infused over a period of 1 hour. A total of 20 patients with metastatic solid tumors refractory to standard therapy received 45 courses of therapy. Taxol was generally well tolerated and caused no significant nausea or vomiting. A mild degree of diarrhea was reported by six patients, and a moderate degree of stomatitis at the higher dose levels developed in four patients. All patients treated in the dosage range of 20 mg/m2 to 40 mg/m2 experienced nearly complete alopecia. Myelosuppression, predominantly in the form of leukopenia, was the dose-limiting toxicity. The nadir of leukopenia was reached between days 8 and 12 followed by complete recovery between days 15 and 21. Leukopenia was first observed following the Taxol dosage level of 20 mg/m2/d, was moderately severe at the dosage level of 30 mg/m2/d, and was severe at the dosage level of 40 mg/m2/d. No objective tumor regression was observed. A starting dosage level of 30 mg/m2/d for 5 days is recommended for phase II trials using this schedule.
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PMID:Phase I study of taxol using a 5-day intermittent schedule. 287 Nov 37

Forty-two patients with malignant melanoma were treated with doxifluridine, 4000 mg/m2 daily X 5, repeated every 3 weeks. The daily dose was reduced to 3000 mg/m2 in patients who had experienced severe myelosuppression with prior chemotherapy. A total of 35 patients were evaluable for response, and 25 of these received two or more courses. Two responses were observed. Toxicity mainly took the form of nausea, vomiting, stomatitis, dizziness, ataxia, and fatigue. Mild leukopenia was frequent (43%). Nadir counts less than 1.5 X 10(9)/l leukocytes or 50 X 10(9)/l platelets were seen in 7% and 2% of the courses respectively. Doxifluridine has no useful activity against malignant melanoma.
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PMID:Phase II study of 5'-deoxy-5-fluorouridine (doxifluridine) in advanced malignant melanoma. 293 77


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