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)

Oral hydroxyurea (HU) was added to a regimen of 5-fluorouracil (5-FU) plus leucovorin (LCV) administered as a continuous 24-hour infusion for 14 days. A previous report of the 5-FU plus LCV infusion established optimal dosages of 200 mg/m2/d and 5 mg/m2/d, respectively, for each agent. Oral HU was added to the regimen in total dosages of 0.5 g/d, 1.0 g/d, 1.5 g/d, or 2.0 g/d. Twenty-two patients received a total of 45 courses of treatment. Stomatitis was the dose-limiting side effect; it occurred in 3 of 14 courses with HU at 0.5 g/d (21%) and 9 of 17 courses with HU at 1.0 g/d (53%). Dosage escalation to 1.5 g/d or 2.0 g/d was possible in only 3 of 22 patients (17%). The median time to stomatitis was 10 days (range, 7 to 12 days). One response was observed in this heavily pretreated population. Phase II trials of HU plus LCV dual modulation of infusional 5-FU should use initial HU dosages of 0.5 g/d for the 14-day regimen described, with dose escalation as tolerated. Variable oral absorption presumably accounts for the small group of patients who can tolerate the higher doses of HU.
Cancer 1991 Aug 15
PMID:Dual modulation of 5-fluorouracil using leucovorin and hydroxyurea. A phase I trial. 185 74

Twenty-eight patients with refractory advanced malignancies were treated with a 24-hour infusion of 5-fluorouracil (5-FU), leucovorin (LV), and N-(phosphonacetyl)-L-aspartic acid (PALA) weekly. Twenty-seven patients were evaluable to assess toxicity and antitumor activity. The PALA was administered as an intravenous bolus over 15 minutes at a fixed dose (250 mg/m2) 24 hours before the start of the 5-FU and leucovorin infusions. Initially the dose of 5-FU was 750 mg/m2; this was increased incrementally to 2600 mg/m2. The LV was administered in a fixed dose of 500 mg/m2 concurrently with the 5-FU over a 24-hour period. This regimen was repeated weekly. Diarrhea, stomatitis, nausea, and vomiting were among the dose-limiting toxicities. Others were hand-foot syndrome, hair loss of the scalp and eyelashes, overall weakness, rhinitis, and chemical conjunctivitis. The maximum tolerated dose of 5-FU in this combination and schedule was 2600 mg/m2. Seven of 14 patients treated with 2600 mg/m2 were able to tolerate the chemotherapy on a weekly basis without interruption. The other seven patients required dose reductions, but most received 5-FU at a dose of 2100 mg/m2. Twenty-three of 27 patients were treated previously. Eight patients had a partial response; five of these were treated previously. A complete response was observed in one patient with pancreatic carcinoma, previously untreated. The overall response rate for patients treated with 2100 or 2600 mg/m2 of 5-FU was nine of 18 patients (50%). Three of four previously untreated patients with pancreatic cancer responded to this treatment (two responded partially, and one had a complete response). One of three heavily pretreated patients with non-small cell lung cancer had a partial response as did a patient with breast cancer. Four of ten patients with colorectal cancer responded to the treatment (four partial responses), of whom three had been treated previously.
Cancer 1991 Sep 15
PMID:A phase I, II study of high-dose 5-fluorouracil and high-dose leucovorin with low-dose phosphonacetyl-L-aspartic acid in patients with advanced malignancies. 187 76

Thymic hormones have been shown to exhibit immunorestorative effects in vivo and in vitro, and to enhance the expression of high affinity interleukin-2 (IL-2) receptors on normal human lymphocytes stimulated with phytohemagglutinin. Based on these data, a clinical trial was initiated to determine the effects of the combination of 5-fluorouracil (5-FU) and folinic acid (FA) with thymopentin (TP-5) and interleukin-2 (IL-2) in patients with advanced colorectal carcinoma. Fifteen patients were treated with FA, 200 mg/m2/day by IV bolus, and 5-FU, 400 mg/m2/day as a 30-minute infusion, both given for 5 consecutive days every 28 days. TP-5, 50 mg/day, was administered subcutaneously on days 8-11, and IL-2, 9 million IU/m2 twice daily, was given subcutaneously on days 12-16. Of 8 patients evaluable for response, 4 achieved a response. Two patients had stable disease, and two progressed during treatment. There were no instances of life-threatening toxicity. Two patients developed grade III stomatitis and diarrhea followed by leukopenia and fever, requiring hospitalization. Other toxicities were moderate. These results are only preliminary, and a larger number of patients and longer follow-up are needed to draw meaningful conclusions about the merits of this new approach in cancer treatment.
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PMID:Thymopentin and interleukin-2 in combination with 5-fluorouracil and leucovorin in metastatic colorectal adenocarcinoma: preliminary results. 189 18

Because of the synergy seen in adult trials when 5-fluorouracil is combined with leucovorin, we initiated a Phase I trial of this combination in children's refractory cancer. Leucovorin, an equal mixture of the (6R,S)-diastereoisomers, was administered p.o. for 6 consecutive days as 4 equal doses at 0, 1, 2, and 3 h totaling 500 mg/m2/day. 5-Fluorouracil was given daily on days 2 to 6 as an i.v. bolus immediately following the last dose of leucovorin. The leucovorin dose was held constant while the 5-fluorouracil dose was escalated in cohorts of patients from 300 mg/m2/day to its maximally tolerated dose. Thirty-five patients (19 with acute leukemia and 16 with solid tumors) were evaluable for toxicity. The maximally tolerated dose of FUra was 450 mg/m2/day for 5 treatments for patients with solid tumors and 650 mg/m2/day for 5 treatments for the children with leukemia. The dose-limiting toxicities were myelosuppression and stomatitis. Other side effects included transient, mild elevations of serum transaminases, mild nausea, vomiting, and diarrhea. The pharmacokinetics of high-dose p.o. leucovorin was studied in 23 children. There was considerable interpatient variability in the plasma concentrations of total bioactive folates (TBAF), (6S)-leucovorin, and (6S)-5-methyltetrahydrofolic acid. The maximum plasma concentration (Cmax) of TBAF was 821 +/- 97 (SE) nM, occurring at a median of 8 h; the Cmax of (6S)-leucovorin was 77 +/- 11 nM, occurring at 4 h. The TBAF concentration fell to 146 +/- 42 nM by 24 h. (6S)-5-Methyltetrahydrofolic acid accounted for 90 +/- 7% of the TBAF at the Cmax. The plasma concentration of (6R)-leucovorin, the unnatural isomer, was equal to that of TBAF. Thus, p.o. leucovorin reduced the 5-fold excess of (6R)-leucovorin over TBAF seen after i.v. doses. The relative amounts of the three major plasma species were approximately the same as in adults, even though the Cmax of each compound was lower.
Cancer Res 1991 Sep 15
PMID:Pharmacology and phase I trial of high-dose oral leucovorin plus 5-fluorouracil in children with refractory cancer: a report from the Children's Cancer Study Group. 189 77

We performed a phase I trial of CI-937 (DUP937), an anthrapyrazole, with the following objectives: (a) to determine the maximally tolerated dose in humans; (b) to define the toxicity spectrum of this agent; (c) to describe the pharmacokinetics of the drug; (d) to test a pharmacokinetics based hypothesis of dose escalation; and (e) to relate drug pharmacokinetics to pharmacodynamics. CI-937 was administered as a single bolus injection every 3-4 weeks at doses ranging from 3.6 to 25.2 mg/m2. Thirty-two patients and 57 courses were evaluable for toxicity. Pharmacokinetic analysis was performed in 30 patients on the first course using a sensitive and selective radioimmunoassay. The maximally tolerated dose in patients with no prior therapy was 25.2 mg/m2 and dose-limiting toxicity was neutropenia. Thrombocytopenia, nausea, vomiting, stomatitis, and alopecia were mild. A partial response was recorded in a patient with mesothelioma. The area under the curve increased linearly with dose, and total body clearance of CI-937 was independent of dose. The mean total body clearance was 107 +/- 55.8 ml/min/m2, mean steady state volume of distribution was 492 +/- 469 liters/m2, and terminal half-life was 3.78 +/- 2.86 days. The extended factors of 2 methods of pharmacologically guided dose escalation were intended for use but ultimately were equivalent to that of the modified Fibonacci dose escalation method. Dose and the area under the curve were significant predictors of a percentage change in WBC and neutrophil count in a univariate analysis. Only dose and baseline neutrophil count predicted a percentage change in WBCs in a multifactor analysis. Dose and prior chemotherapy predicted percentage change in neutrophil count in a multifactor analysis. We conclude that the dose-limiting toxicity of CI-937 is neutropenia and that the recommended phase II starting dose is 22 mg/m2.
Cancer Res 1991 Dec 01
PMID:Phase I pharmacokinetic and pharmacodynamic study of a new anthrapyrazole, CI-937 (DUP937). 193 93

For prevention of the chemotherapy-induced stomatitis we administered allopurinol mouthwash to 15 out of 38 patients who underwent PMUE regimen. The severity of stomatitis was graded on five scales according to the criteria of Japan Society For Cancer Therapy. The incidence of stomatitis was defined as patients number with stomatitis above Grade 2/all patients number. Six of 23 patients which were not given allopurinol mouthwash (control group) developed stomatitis of Grade 1 (three patients), Grade 3 (two), or Grade 4 (one). Only one patient given allopurinol mouthwash (AMW group), however, suffered from Grade 1 stomatitis. The incidence of stomatitis was 13.0% for a control group and 0% for an AMW group. The average graded toxicity was 0.07 for the AMW group significantly lower than 0.57 for the control group. There was no significant difference between the two groups in other clinical adverse effects or abnormal laboratory data. These results suggested that allopurinol mouthwash regimen was well tolerated and effective for prevention of the chemotherapy induced stomatitis.
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PMID:[Prophylactic effect of allopurinol mouthwash against stomatitis induced by the chemotherapy (PMUE regimen) for gastrointestinal malignancies]. 195 66

A phase I trial of piritrexim was conducted by use of a prolonged, low-dose oral schedule. A number of different regimens were tested, including daily dosing for 21 days followed by 7 days of no drug therapy; continuous dosing; and daily dosing for 5 of 7 days for 3 consecutive weeks followed by a week of rest. Dose escalation was accomplished by increasing the dosing frequency from once a day to twice a day and then to three times a day and by increasing the number of days of administration. Fifty-one patients with advanced cancer were entered in the study. One hundred twenty-four (96%) of 129 courses were considered assessable. Myelosuppression proved to be the dose-limiting toxic effect. Other toxic effects included stomatitis, nausea and vomiting, anorexia, diarrhea, skin rash, fatigue, and elevation of liver transaminase levels. Antitumor activity was observed in patients with melanoma and bladder cancer, and disease stabilization occurred in those with sarcoma and pheochromocytoma. The recommended dosing schedule for phase II clinical trials is 25 mg three times a day for 5 days for 3 consecutive weeks followed by 1 week of no drug therapy.
J Natl Cancer Inst 1991 Jan 02
PMID:Phase I trial of piritrexim capsules using prolonged, low-dose oral administration for the treatment of advanced malignancies. 198 18

A total of 40 patients with metastatic breast cancer were treated with 120 mg/m2 i.v. epirubicin every 3 weeks for a maximum of 10 cycles. Nine achieved a complete response and 17 showed a partial response, for an objective response rate of 65% (95% confidence interval, 47%-83%); the median duration of response was 7 months (range, 1-15 months) and median survival amounted to 13 months (range, 2-20 months). Leucopenia (grade 2 or 3) was seen in 14 patients on day 21 of the cycle. A subset of nine patients underwent blood counts on day 10, when all had marked neutropenia (less than 1 x 10(9)/l). Other toxicity was frequent and included nausea/vomiting (80%), alopecia (95%) and stomatitis (35%). Five patients showed a significant fall in cardiac output, but this reverted to normal after treatment. Epirubicin should have a role in the development of high-dose regimens for the treatment of advanced breast cancer.
Cancer Chemother Pharmacol 1991
PMID:High-dose epirubicin as primary chemotherapy in advanced breast carcinoma: a phase II study. 199

A staging system was developed to measure the progressive severity of chemotherapy-induced stomatitis. A panel of 15 experts from nursing, dentistry, and medicine were interviewed to elicit the criteria they used to evaluate progressive severity. This process was used to develop an instrument to measure the observable and functional dimensions of stomatitis. After pilot testing, the instrument was refined and evaluated with 53 cancer patients. Patients receiving stomatotoxic chemotherapy, or already exhibiting oral problems secondary to chemotherapy, were tested with three measures: the new Western Consortium for Cancer Nursing Research (WCCNR) Staging System, the Oral Assessment Guide (OAG), and the World Health Organization (WHO) Mucositis Grading System. Results indicated that the three scales were moderately correlated (0.57 to 0.76), indicating they were measuring the same general construct. The mean OAG scores were significantly different by WCCNR stage, and discriminant analysis demonstrated that the staging system did differentiate between the three stages of stomatitis as measured by the other two scales. The WCCNR Staging System is unique in that it reflects expert practice, encouraging clinicians to make a holistic assessment of the mouth's condition rather than summing scores on discrete aspects of the oral condition.
Cancer Nurs 1991 Feb
PMID:Development of a staging system for chemotherapy-induced stomatitis. Western Consortium for Cancer Nursing Research. 201 54

The new anticancer agent lonidamine has been recently revisited for the treatment of various solid tumors, due to its peculiar and unusual mechanism of action (ie, interference with energy metabolism of tumor cells, morphologically displayed by the appearance of "condensed mitochondria"). First generation trials have in fact demonstrated therapeutic activity and an unusual toxicity profile. Lonidamine is devoid of conventional side effects induced by antiproliferative agents (ie, myelosuppression, stomatitis, cystitis, alopecia, renal, hepatic, and cardiac toxicity). No serious or life-threatening adverse reactions have been recorded even over long term treatment periods. Given as a single agent (in daily doses ranging between 300 and 900 mg) lonidamine induces the following side effects: myalgia, testicular pain, asthenia, ototoxicity, nausea and vomiting, gastric pain, and drowsiness. Hyperesthesia and photophobia have also been reported. In combination with radiotherapy (in oral daily doses ranging between 300 and 450 mg) lonidamine was well tolerated, without any reported evidence of additional toxicity. When associated with cytotoxic agents no enhanced toxicity was observed. In particular, myelosuppression and other conventional nonhematological adverse reactions were never greater than would be expected with chemotherapy alone. The same applies to toxicity and tolerance of lonidamine when used concurrently with hypertermia. The data collected from large series of cancer patients treated with this new agent show that lonidamine is a safe drug whether used alone or in combination with other effective anticancer treatments. The reported therapeutic efficacy and the peculiar toxic profile make lonidamine an interesting new drug for future clinical trials.
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PMID:Toxicity and clinical tolerance of lonidamine. 203 Nov 92


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