Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Between October 1988 and June 1990, 22 patients with locally advanced, inoperable breast cancer entered a pilot study of four cycles of anthracycline based cytotoxic chemotherapy followed by surgery and tamoxifen. Fine needle aspirate samples of tumour were obtained for DNA flow cytometry before treatment and during the first cycle of chemotherapy. 21 patients are eligible for assessment of response and toxicity. Chemotherapy was well tolerated with greater than WHO grade 2 vomiting or stomatitis in 4 patients. Granulocytopenia less than 10(9)/l was noted in 16/21 patients but there were no episodes of neutropenic sepsis. There were 7 complete responses (CR) and 11 partial responses (PR), giving an overall response rate to chemotherapy (CR+PR) of 18/21 (86%). Responses were observed more commonly in patients who had aneuploid tumours (P = 0.06) and in patients whose tumours had a high S-phase fraction (P = 0.1). Tumours which responded to chemotherapy (CR or PR) had a significantly higher median SPF compared with tumours which did not regress (P less than 0.05). There was no consistent pattern of change in SPF values during the first cycle of chemotherapy, either for patients who responded to treatment or for those whose tumours did not regress. This combination therapy is well tolerated with a high response rate. The results of this pilot study support the recent suggestion that tumours with rapidly proliferating, aneuploid populations of cells exhibit the best short-term response to chemotherapy.
Eur J Cancer 1992
PMID:DNA flow cytometry and response to preoperative chemotherapy for primary breast cancer. 159 Oct 92

The combination of folinic acid (FA) and 5-fluorouracil (5FU) is the most active systemic chemotherapy against advanced colorectal cancer. Experimental and clinical studies have suggested that the activity of 5FU can be improved by the addition of alpha-interferon (IFN). To evaluate the possibility of a double modulation of 5FU, a pilot study was conducted in the period July 1989-December 1989 with the following regimen: FA (200 mg/m2 i.v. bolus x 5 days) + 5FU (400 mg/m2 i.v. in 15 min x 5 days) + alpha-2b IFN (10 x 10(6) IU subcutaneously on alternate days). FA and 5FU administrations were repeated every 28 days; IFN was administered every week. In the 16 treated patients, 4 partial responses, 4 no changes, and 8 with progression of disease were observed, with an objective response rate of 25% (95% CI, 7.8%-55.1%). Median duration of response was 9.5 months, as was overall survival. Toxicity (fever, fatigue, neurotoxicity, stomatitis and diarrhea) was considerable and led to a reduction in IFN doses in 10/16 patients. Due to the unfavorable cost/benefit ratio, the study was closed and a new trial, with different doses and schedule of IFN, was started within the GISCAD (Italian Group for the Study of Digestive Tract Cancer).
 ...
PMID:High dose alpha-2b interferon + folinic acid in the modulation of 5-fluorouracil. A phase II study in advanced colorectal cancer with evidence of an unfavourable cost/benefit ratio. 160 56

In a prospective randomized multicentre trial 139 patients with metastatic colorectal carcinoma (70 men, 69 women; age 35-81 years) were given palliative treatment with fluorouracil (400 mg/m2 daily for 5 days) alone or combined with folic acid (100 mg/m2 before each dose of fluorouracil). Both groups were comparable in respect of age, sex, Karnofsky index and number of localisations of metastases. The criterion for starting the treatment was progression of the malignancy or clinical symptoms caused by the tumour. Resulting remission rates (fluorouracil monotherapy vs combination with folic acid) were: complete or partial remission, 9 vs 16%; arrest of tumour growth, 20 vs 60%; progression 71 vs 24%. Peripheral side effects, such as stomatitis and diarrhoea, were similarly frequent with the two treatment regimens and reasonably tolerable. Median survival time for the fluorouracil monotherapy was 7.24 months from onset of treatment, and 9.1 months from the time that any metastases were diagnosed. The combination treatment with folic acid achieved a significantly longer median survival time (P less than 0.0001), 14.98 months from treatment onset and 16.3 months from metastasis diagnosis. The higher rate of response and the significantly prolonged survival time signify an improvement of the therapeutic profile of fluorouracil by addition of folic acid in the palliative therapy of colorectal carcinomas.
 ...
PMID:[Fluorouracil as monotherapy or combined with folinic acid in the treatment of metastasizing colorectal carcinoma]. 161 9

Leucovorin (LV), given intravenously the orally becomes 5, 10-methylene tetrahydrofolate in both cancer and normal cells. FdUMP which is an active metabolite of 5-FU binds tightly to thymidylate synthase in the presence of the cofactor 5, 10-methylene tetrahydrofolate. This interaction leads to potentiate the cytotoxic effect of 5-FU by prolonged inhibition of thymidylate synthase. Clinically, the combination of LV and 5-FU is given parenterally by two schedules; 5 consecutive days schedule and weekly schedule. Five 5 consecutive days-schedule is divided into 2 methods. One is a 200 mg/m2/day of LV by Machover, and the other is 20 mg/m2/day of LV by O'Connell. The weekly schedule is a 2-hour infusion of dl-LV (500 mg/m2) and iv bolus of 5-FU (600 mg/m2), given 1 hour after the beginning of LV infusion by Petrelli. A multicenter cooperative study in Japan was conducted to evaluate the clinical efficacy of LV and 5-FU using the weekly schedule by Petrelli. Response rates were 31.5% and 41.2% against advanced gastric and colorectal cancer respectively. Then, we carried out a randomized early phase II study using 250 mg/m2 of l-LV weekly (similar to the schedule of Petrelli's, armA) and 100 mg/m2 (similar to the schedule of Machover's, arm B) or 10 mg/m2 (similar to the schedule of O'Connell's, arm C) of l-LV for 5 consecutive days against gastric cancer. The response rate was 33.3% in arm A, 24.1% in arm B and no response in arm C. Toxicity was within acceptable limits, Toxic effects included diarrhea, stomatitis, anorexia and myelohypoplasia. Our data suggests that high-dose LV and 5-FU seems to be a very promising combination but, there was no responder using low dose (10 mg/m2) of l-LV schedule against gastric cancer patients.
 ...
PMID:[High-dose leucovorin and 5-FU]. 162 51

The pharmacokinetics of doxorubicin (DOX) and doxorubicinol (DOXol) was studied in six patients with various advanced neoplastic diseases who received 28-72 mg/m2 DOX (nine courses). Plasma and parotid saliva were collected over a 48-h period, and DOX and DOXol were quantified by high-performance liquid chromatography with fluorescence detection. As reported previously, a wide range of plasma levels were found among our patients. It appears that in addition to being quickly cleared from the plasma, both DOX and DOXol are excreted in detectable amounts in parotid saliva, a route of elimination that has been given little attention, if any. Excretion in the saliva exposes the mucosa of the upper gastrointestinal tract to drug and may play a role in causing stomatitis in patients receiving DOX by the i.v. route. Since huge interindividual and pronounced intraindividual differences were found in S/P ratios that mostly were not systematically related to the plasma drug concentration, the concentration in parotid saliva was not useful in predicting the level of free DOX and DOXol in plasma. For the parent drug and its metabolite, the S/P ratios increased significantly with time during the 48-h period after dosing.
Cancer Chemother Pharmacol 1992
PMID:Doxorubicin and doxorubicinol plasma concentrations and excretion in parotid saliva. 162 70

A phase I trial of 5-fluorouracil (FUra) and leucovorin (LV) given with and without dipyridamole (DP) by concurrent 120-h continuous infusion was performed in 27 patients with advanced solid malignancies, 8 of whom had previously received FUra. The LV and DP doses were fixed at 500 mg/m2 daily and 7.7 mg/kg daily, respectively, whereas the FUra dose was escalated. Level 3 (450 mg/m2 FUra daily) represented the maximum tolerated dose for both FUra/LV+DP and FUra/LV. Dose-limiting stomatitis (greater than or equal to grade 3 or grade 2 occurring during the infusion) was encountered in 75% of the first courses given at level 4 (600 mg/m2 daily). Stomatitis was observed in 44/78 (56%) courses. Diarrhea was infrequent and mild. DP infusions were complicated by mild to moderate headache, which was controlled with narcotic analgesics, and mild to moderate nausea/vomiting. FUra-related toxicity was not enhanced by DP administration. Limited pharmacokinetic sampling at levels 3 and 4 revealed mean steady-state FUra concentrations of around 1.0 microM with infusions of FUra/LV+DP. Among three paired courses given with and without DP, no statistically significant difference was found in the total body clearance of FUra (P = 0.44). One partial response was seen in a patient with metastatic gastric carcinoma. For phase II trials, we recommend that concurrent 120-h continuous infusions of FUra (450 mg/m2 daily) and LV (500 mg/m2 daily) be given with and without DP (7.7 mg/kg daily) every 21 days.
Cancer Chemother Pharmacol 1992
PMID:A phase I trial of 5-fluorouracil, leucovorin, and dipyridamole given by concurrent 120-h continuous infusions. 164 98

Edatrexate (10-ethyl-10-deaza-aminopterin; CGP 30 694) is a methotrexate (MTX) analogue that shows promise against non-small-cell lung cancer (NSCLC) and other tumors. Since edatrexate's mechanism of action is the same as that of MTX, we used leucovorin in an attempt to alleviate its dose-limiting toxicity, stomatitis. In four patients with NSCLC who had experienced significant stomatitis after treatment with edatrexate, cyclophosphamide, and cisplatin, we observed a remarkable reduction in stomatitis following the administration of low-dose leucovorin. On the basis of the results obtained in these individuals, we treated 15 additional patients with this three-drug regimen plus leucovorin rescue. These subjects could tolerate the treatment with lesser degrees of stomatitis and received higher edatrexate doses in subsequent courses as compared with the patients who previously received this regimen without leucovorin rescue. This approach is expected to improve the therapeutic indices of edatrexate and edatrexate-containing chemotherapy regimens by modifying the dose-limiting toxicity of this antineoplastic agent.
Cancer Chemother Pharmacol 1991
PMID:Alleviation by leucovorin of the dose-limiting toxicity of edatrexate: potential for improved therapeutic efficacy. 164 5

The authors treated 32 patients with Stage IIIB or IV non-small cell lung cancer (NSCLC) with an outpatient regimen of edatrexate (10-ethyl-10-deaza-aminopterin) (10-EdAM) on days 1 and 8, cyclophosphamide on day 1, and cisplatin on day 1, repeated every 3 weeks with dose modification. The 22 men and 10 women (median age, 57 years of age) had no prior chemotherapy and a Zubrod performance status less than or equal to 2. A schedule with initial doses of 80 mg/m2, 800 mg/m2, and 80 mg/m2, respectively, yielded a 47% major response rate with two complete responses (95% confidence interval [CI], 25% to 70%), but it also yielded significant stomatitis and myelosuppression. A schedule with reduced starting doses (70 mg/m2, 700 mg/m2, and 70 mg/m2) was better tolerated, but dropped the major response rate to 27% with no complete responses (95% CI, 11% to 52%). Median survival time was 39 weeks for all 30 evaluable patients without a significant difference between the treatment groups (which were comparable in patient characteristics). Major response, however, was associated with longer survival time than minor response or no change (P = 0.024) or progressive disease (P = 0.001) (median survival times, 55, 39, and 27 weeks, respectively). When the doses delivered were compared, patients treated with the reduced dose schedule received less mean 10-EdAM per course (P = 0.01), although the doses of cyclophosphamide and cisplatin were comparable to the original dose schedule for the second course and thereafter. These results suggest that this three-drug regimen may have synergistic antitumor effects, with a steep dose-response relationship, particularly with 10-EdAM. With amelioration of the dose-limiting stomatitis of 10-EdAM, it seems possible to maximize the antitumor effects of this regimen.
Cancer 1991 Sep 01
PMID:Edatrexate improves the antitumor effects of cyclophosphamide and cisplatin against non-small cell lung cancer. 165 20

Oral mucositis associated with head and neck radiotherapy can substantially hinder completion of cancer therapy. Alleviation of this often severe stomatitis can provide enhanced patient comfort and facilitate appropriate care. A double-blind format was used in a pilot project to measure, against a control rinse, the effectiveness of an oral rinse consisting of hydrocortisone, nystatin, tetracycline, and diphenhydramine in controlling radiation-related mucositis. A combination of clinical evaluation and patient responses to a questionnaire was used to judge the results of the topical medications. Patients using the experimental medication developed less mucositis than did patients in the control group.
 ...
PMID:Palliation of radiation-related mucositis. 168 12

Sixty-six patients with locally advanced (Stages III and IV) carcinoma of the head and neck were treated with three cycles of induction chemotherapy, consisting of cisplatin, fluorouracil (FU) infusion, bleomycin, mitomycin, and hydroxyurea, followed by radiotherapy and/or surgery. There were 48 men and 18 women with a median age of 55 years (range, 18 to 75 years) and Karnofsky performance status of 80 (range, 40 to 90). Primary site was nasopharynx (28 patients), followed by larynx (12) and others (26). Forty-one (62%) patients were presented with Stage IV disease. The response rate to induction chemotherapy was 27% complete response, 50% partial response, 20% stable disease, and 3% progressive disease. There was no significant difference in response rate between patients with cancer of nasopharynx or other sites (P greater than 0.1). Survival was 61% at 24 months. Patients with cancer of nasopharynx had a better survival than those with other primaries (P = 0.033). Toxicities from chemotherapy included alopecia (73%), nausea/vomiting (66%), leukopenia (54%), stomatitis (36%), anemia (32%), thrombocytopenia (16%), and diarrhea (9%). Grade IV toxicity was not observed. Induction chemotherapy with this new regimen resulted in a high response rate but may not be superior to cisplatin and FU alone. It can be safely combined with radiotherapy as a potentially curative therapy in squamous cell carcinoma of the head and neck. Chemotherapy followed by radiation therapy may yield survival similar to radical surgery in laryngeal and other head and neck cancers.
Cancer 1990 Oct 01
PMID:Induction chemotherapy with a new regimen alternating cisplatin, fluorouracil with mitomycin, hydroxyurea and bleomycin in carcinomas of nasopharynx or other sites of the head and neck region. 169 26


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>