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)

A clinical trial of the oral form of VP 16-213 (NSC-141540), a semisynthetic podophyllotoxin, was undertaken. In 20 patients, treatment was started at 200 mg/day p.o. for 5 days; courses were repeated after a rest period of 16 days. Five patients were treated at the same dose, repeated with only 9-day rest periods. Subsequently, 65 patients were given 300-400 mg/day for 5 days, with rest periods of 9 days between courses. The side effects encountered included anorexia, nausea and vomiting, stomatitis, diarrhea, leukopenia, thrombocytopenia, alopecia, and pruritus. Substernal discomfort with or without palpitations was reported by 18 patients; no explanation for this symptom could be found. No complete remissions (CR) were observed. Parital remissions (PR) and improvement (IMP) were seen as follows: small cell carcinoma, lung (10 patients)--2 PR, 3 IMP; adenocarcinoma, lung (4 patients)--1 PR; alveolar cell carcinoma, lung (1 patient)--1 IMP; mesothelioma (4 patients)--1 IMP; ovarian cancer (12 patients)--3 PR, 3 IMP; breast cancer (20 patients)--4 IMP; colon cancer (8 patients)--2 IMP; bladder cancer (4 patients)--2 IMP; histiocytic lymphoma (7 patients)--2 PR, 3 IMP; chronic myeloid leukemia (1 patient)--1 IMP.
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PMID:A clinical trial of the oral form of 4'-demethyl-epipodophyllotoxin-beta-D ethylidene glucoside (NSC 141540) VP 16-213. 16 75

Interferon-alpha (IFN-alpha) production was investigated in whole-blood cultures of 66 bladder cancer patients and 65 control subjects. IFN synthesis was induced with Sendai virus, and IFN activity was assayed in FL cells challenged with vesicular stomatitis virus (VSV). The mean levels of the IFN-alpha produced were 5,724 +/- 2,288 IU/ml in the control subjects and 4,800 +/- 2,353 IU/ml in the bladder cancer patients. IFN-alpha production was significantly suppressed in the bladder cancer patients compared with that in the control subjects (P less than 0.05). The impairment in IFN-alpha production correlated with the tumor grade, and it was shown that the tendency toward decreased IFN-alpha production was closely associated with the advancement of the tumor stage. Our results suggested that the decreased IFN-alpha production may contribute to the disordered immunoregulation in bladder cancer patients.
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PMID:Impaired interferon-alpha production in whole-blood cultures from bladder cancer patients. 185 48

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.
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PMID:Phase I trial of piritrexim capsules using prolonged, low-dose oral administration for the treatment of advanced malignancies. 198 18

From June 1986 to November 1989, 7 patients (pts.) with transitional bladder cancer were treated with CDDP 70 mg/m2 i.v. on day 1 and MTX 40 mg/m2 i.v. on days 8 and 15. The initial stage was T2 N0 M0 (2), T2 N0 M0 (8), T4 N0 M0 (4) and T3-4 N+ M0 (3). The median age was 56 years. After a median number of two cycles (1-5) of CDDP-MTX, 3/17 pts. (17.6%) had a complete remission (CM), 9/17 pts. (53%) a partial response (PR) greater than 50%, 4/17 pts. (23.4%) a PR less than 50%, 1/17 pts. (6%) a stable disease. Nausea and vomiting occurred in almost all pts., 20% of pts. had grade 3 stomatitis, 35% of pts. had diarrhoea, 20% of pts. had conjunctivitis, 7% of pts. had a bone marrow depression and hair loss. One patient had severe renal and liver toxicity and grade 4 bone marrow suppression with sepsis, completely controlled after intensive care. The treatment after neoadjuvant chemotherapy was: radical cystectomy (11)- in one following radiotherapy -; partial resection + lymphoadenectomy (2); TUR (4) in 1 pt. with lymphoadenectomy. After a median follow-up of 28 months (6-36), 12/17, equivalent to 71% of pts. are disease free, 3/17 (17%) are alive with disease, 2/17 (12%) died. In conclusion the association of neoadjuvant CDDP-MTX can induce a high percentage of response, and can preserve bladder function in some patients. Further controlled trials and a longer follow-up are needed to better define the exact role of this combination in terms of disease free survival, total survival and quality of life.
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PMID:[Neoadjuvant chemotherapy using cisplatin (CDDP) and methotrexate (MTX) in carcinoma of the bladder]. 214 9

Brequinar, DUP 785, is a substituted 4-quinoline carboxylic acid derivative which in preclinical studies has shown broad antitumor activity. It is a novel antimetabolite blocking pyrimidine nucleotide synthesis. In a clinical phase I study, 83 patients were treated on a weekly schedule and 18 patients on a biweekly schedule. The drug was given intravenously as a short infusion. Three patients were entered on each dose level from a starting dose of 6 mg/m2 up to 2600 mg/m2 weekly. The dose ranges on a biweekly schedule were 500-850 mg/m2. There was no dose escalation in individual patients. Pharmacokinetic studies were performed in 19 patients on a weekly schedule and in two patients on a biweekly schedule. A biphasic decay in plasma was observed with a median half life of 10 h (5.1-23.4). The main dose-limiting toxicity was thrombocytopenia. Of non-hematologic side-effects, stomatitis/mucositis occurred frequently. Skin eruptions occurred rarely, but were a major problem when found. All side-effects were fully reversible; there were no signs of cumulative toxicity. Antitumor activity was observed in one patient with a lung metastasis from a bladder cancer and in a patient with an unknown primary tumor. The recommended doses for phase II trials with DUP 785 are: 1500-2000 mg/m2 on a weekly schedule and 500-750 mg/m2 on a biweekly schedule dependent on status before treatment.
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PMID:A phase I clinical and pharmacokinetic study of Brequinar sodium, DUP 785 (NSC 368390), using a weekly and a biweekly schedule. 259 33

A Phase II Study of (2''R)-4'-O-tetrahydropyranyladriamycin (THP) in patients with various solid tumors was carried out by 44 cooperative study institutions. Seven hundred fifty-six patients administered the drug intravenously were entered into this study. Of these, 499 patients were evaluated for objective responses. THP was given mainly at a dose of 40 to 60 mg/body every 3 to 4 weeks or 20 to 30 mg/body once a week. Response rates were 18.8% for head and neck cancer, 13.1% for stomach cancer, 21.4% for breast cancer, 22.2% for bladder cancer, 30% for renal pelvic and urinary tract tumor, 26.8% for ovarian cancer and 24.2% for uterine cancer. Overall response rate was 15.4% including 10 complete responses and 67 partial responses. Adverse reactions were similar to those previously reported in the phase I study, including gastrointestinal toxicities and myelosuppression. Alopecia and stomatitis, which are major side effects of other anthracyclines, were rather mild. Incidence of ECG changes was 2.8% and no congestive heart failure was observed.
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PMID:[Phase II study of (2''R)-4'-O-tetrahydropyranyladriamycin (THP) in patients with solid tumors. Multi-Institutional Cooperative Study]. 396 50

Clinical study of UFT which was a mixture of FT and uracil, was conducted on 16 patients with urogenital malignancies. Seven patients had renal cell carcinoma, 5 patients had bladder cancer and 4 patients had prostatic cancer. UFT was continuously administrated at doses of 300 mg or 600 mg per day. One of the patients with renal cell carcinoma and 1 of the patients with bladder cancer showed a complete response, and 1 patient with each cancer showed a partial response, but none of the 4 patients with prostatic cancer responded. In total, complete or partial responses were obtained in 4 of the 16 patients, given an effective rate of 25.0%. Concerning side effects, 3 of the 16 patients complained of anorexia, nausea and vomiting, and stomatitis, but no hepatic or renal disorders, or marrow depression was observed.
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PMID:[Clinical effect of UFT on urogenital tumors]. 642

A combination therapy consisting of daily intrarectal administration of 1,500 mg of FT-207 suppository, daily or every three day bladder instillation of 40 mg adriamycin for a total of 20 applications, and once per week intramuscular administration of 5 KE OK-432 was described. The therapy was performed in 30 cases of advanced bladder cancer. The effectiveness evaluated by Karnofsky's criteria was as follows: 8 cases of 0-0, 2 of 0-A, 1 of 0-B, 2 of 0-C, 7 of 1-A and 10 of 1-B, showing an effective rate of 57%. Local pain was observed in 20 cases (67%), pancytopenia in 1 (3%), hepatitis in 4 (13%), stomatitis in 5 (17%) and anorexia in 6 (20%). From this clinical trial, it is presumed that combination therapy administering FT-207 intrarectally, adriamycin intravesically and OK-432 intramuscularly might be used for the treatment of advanced bladder cancer provided sufficient care is taken of general side effects.
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PMID:Immunochemotherapy for advanced bladder cancer using FT-207, adriamycin and OK-432. 681 68

Bladder cancer is the second most common genitourinary malignancy. At initial diagnosis, approximately 70% of cases are non-muscle-invasive; however, current treatment options for superficial disease are of limited efficacy because many patients will develop recurrent tumors. The purpose of this study was to examine two replication-competent oncolytic vesicular stomatitis virus (VSV) strains as intravesical agents in an orthotopic murine model of high-grade bladder cancer. Four human bladder cancer cell lines (RT4, MGH-U3, UM-UC3, and KU-7) were treated with either wild-type VSV or a mutant Delta51M variant (AV3) in vitro. Both wild-type VSV and AV3, which has an impaired ability to shutdown innate immunity, preferentially killed the more aggressive, IFN-nonresponsive cell lines UM-UC3 and KU-7, whereas IFN-responsive RT4 and MGH-U3 cells were less susceptible. In vivo, KU-7-luc bladder tumor cells, which stably express firefly luciferase, were inoculated into nude mice by intravesical instillation and tumor growth was quantified using bioluminescence imaging. Mice with established xenografts were administered VSV intravesically on days 4, 9, and 14, and necropsy was performed after 3 weeks. AV3 as well as wild-type VSV significantly inhibited KU-7-luc tumor growth by 90% (AV3) and 98% (wild-type), respectively, as compared with controls treated with UV-inactivated VSV. Despite using immunocompromised hosts, there was no evidence of toxicity in either group. In conclusion, VSV instillation therapy showed promising antitumor activity and safety in an orthotopic model of bladder cancer. These findings provide preclinical proof-of-principle for the intravesical use of VSV against non-muscle-invasive bladder cancer, especially in IFN-refractory patients.
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PMID:Oncolytic vesicular stomatitis viruses are potent agents for intravesical treatment of high-risk bladder cancer. 1855 93

Patients with high-risk bladder cancer who do not respond to bacillus Calmette-Guerin (BCG) immunotherapy represent a significant therapeutic challenge. The addition of interferon to BCG has recently evolved as a second-line treatment option; however, many high-grade tumors are nonresponsive to interferon. Thus, replication-competent oncolytic vesicular stomatitis viruses (VSV) that selectively target interferon-refractory tumors are promising intravesical agents. In vitro, wild-type VSV as well as a mutant variant (AV3) that has an impaired ability to shut down innate immunity preferentially killed undifferentiated, interferon-nonresponsive bladder cancer cells. Testing of these viruses in an orthotopic murine model of high-grade bladder cancer, which we have recently validated, revealed that both AV3 and wild-type VSV significantly inhibited orthotopic tumor growth. Despite the use of immunocompromised nude mice, there was no evidence of toxicity. In conclusion, VSV instillation therapy demonstrated strong antitumor activity and safety in an orthotopic model of high-risk disease. These findings provide preclinical proof-of-principle for the intravesical use of VSV, especially in interferon-refractory patients.
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PMID:[Oncolytic vesicular stomatitis viruses as intravesical agents against non-muscle-invasive bladder cancer]. 1867 Jul 47


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