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)

Forty-nine patients with advanced breast cancer who had failed from first-line cyclophosphamide, methotrexate, and 5-fluorouracil (CMF regimen) chemotherapy, were randomized to treatment with either epirubicin (Epi) or doxorubicin (Dox) at a dose of 20 mg/m2 given intravenously (i.v.) weekly to compare the efficacy and toxicity of these two anthracyclines given in such a schedule. Of 43 evaluable patients 36% (eight of 22) treated with Epi and 38% (eight of 21) treated with Dox achieved a complete plus partial response rate (95% confidence limits 16-56% +/- 20% and 18-58% +/- 20%, respectively). Patients who obtained a major therapeutic response to previous CMF exhibited a significantly higher response rate with both the drugs: seven of eight (87.5%) compared with one of 13 (8%); p less than 0.05 for Epi and six of seven (86%) compared with two of 15 (13%); p less than 0.05 for Dox. The median duration of response was 4.5 months with Epi compared with 7 months with Dox, and the median survival of the two groups of patients were superimposable (12 months with Epi versus 11 months with Dox). The median cumulative dose was 220 mg/m2 (range 160-620) and 240 mg/m2 (range 160-860) for Epi and Dox, respectively. Gastrointestinal and hematological toxicities were moderate for both the drugs, with fewer episodes of nausea and vomiting, stomatitis, and leukopenia following Epi administration. A very low incidence of alopecia was recorded for both the drugs. Regarding cardiac evaluation, no significant differences were evident; however, the only case that developed symptomatic congestive heart failure was in the Dox arm, after a cumulative dose of 820 mg/m2 at 11.5 months. Epi given weekly at low doses preserves efficacy in the treatment of patients with advanced breast cancer, and given at equimolar doses, has a slightly better therapeutic index than the parent compound.
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PMID:Weekly epirubicin versus doxorubicin as second line therapy in advanced breast cancer. A randomized clinical trial. 198 37

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.
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PMID:High-dose epirubicin as primary chemotherapy in advanced breast carcinoma: a phase II study. 199

Forty-six eligible patients with metastatic breast cancer (MBC) were treated with a combination of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) as first-line chemotherapy. Of 44 patients evaluable for response, 28 (64%) had an objective response, including seven (16%) who had a complete response. The median duration of response was 4 months (range, 0 to 38 months), and the median survival from the time of entry was 14 months (range, less than 1 to greater than 45 months). Myelosuppression was the most common dose-limiting toxicity, with 54% of patients experiencing Grade 3 or 4 leukopenia (including 28% with granulocytopenic fever and one septic death), and cumulative Grade 3 anemia occurred in 28% of patients. Grades 3 to 4 stomatitis was observed in 18% of patients. An active, although highly toxic regimen when used as first-line therapy in MBC, M-VAC has a response rate and survival duration similar to existing, less toxic combination regimens. As such, M-VAC cannot be recommended in preference to other combination chemotherapy regimens in this clinical setting.
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PMID:Methotrexate, vinblastine, doxorubicin, and cisplatin in metastatic breast cancer. A phase II trial of the Hoosier Oncology Group. 207 Mar 21

Trimetrexate (TMTX) is an analog of methotrexate and a potent inhibitor of the enzyme dihydrofolate reductase. In this phase I study, TMTX was given intravenously to 32 patients as a constant infusion over 24 hours every 28 days. The maximum-tolerated dose of TMTX was 200 mg/m2, with myelosuppression as the dose-limiting toxicity. Other toxicities included nausea and vomiting, stomatitis, erythema and phlebitis at the site of infusion, rash and skin hyperpigmentation, and elevated serum hepatic enzymes. Two drug-related deaths occurred secondary to leukopenia and sepsis. Twenty-six patients were evaluable for antitumor response. Twenty-one patients had progressive disease, while three patients had disease stabilization. There were two partial responses observed--one in a patient with breast cancer and a second in a patient with nasopharyngeal carcinoma. TMTX pharmacokinetics were studied in 15 patients. The drug had a mean terminal half-life of 13 hours. Steady-state was not achieved during the 24-hour infusions. Only 6% of the parent compound was excreted unchanged in the urine, and CSF levels averaged less than 2% of simultaneously measured plasma levels. A dose of 150 mg/m2 is recommended for phase II trials of TMTX using this 24-hour infusion schedule.
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PMID:A phase I and pharmacokinetic study of trimetrexate using a 24-hour continuous-injection schedule. 214

Fifty-one patients with advanced germ cell malignancy who had either failed to achieve complete remission with initial cisplatin, vinblastine, and bleomycin chemotherapy or who had relapsed after complete response (CR) to this therapy and then proven refractory on retreatment, were treated with etoposide (75 mg/m2 for 3 days), dactinomycin (1 mg/m2 day 1), and methotrexate (30 mg/m2 day 1) (EAM) every 3 weeks. Courses were continued until maximum response without empirical limit, and if complete remission was achieved, two courses of consolidation therapy were given before cessation of treatment. Thirteen patients (25%) were complete responders with residual masses containing fibrosis or benign teratoma being subsequently resected in seven patients. Two patients had persisting viable carcinoma within residual masses that were completely resected, leaving no evidence of disease (NED); the combined CR plus NED rate was 29%. The only pretreatment factor significantly influencing this response rate was tumor volume. Toxicities were moderate, with leukopenia being observed in 28% of patients, but it was severe in only 2%. There was one death from septicemia. Severe nausea and vomiting occurred in only 9% of patients and treatment-related stomatitis was observed in 42%. All patients achieving CR plus NED have been followed for a minimum of 5 years and no relapses have occurred, suggesting that these patients are cured. Unlike other regimens of salvage chemotherapy, this treatment program did not contain cisplatin and it is contended that a completely noncrossresistant drug regimen based on etoposide provides the opportunity to further improve the curability of patients with advanced germ cell cancer.
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PMID:Effective salvage chemotherapy with etoposide, dactinomycin, and methotrexate in refractory germ cell cancer. Australasian Germ Cell Trial Group. 215 92

The purpose of the study was to investigate the antitumour activity and toxicity of high dose (120 mg m-2) single agent epirubicin therapy in untreated extensive small cell lung cancer patients. Out of 80 patients entered, 71 were evaluable for both antitumour activity and toxicity, 4 only for toxicity and 5 were lost for follow-up. The drug possessed a high antitumour activity, the overall response rate was 47.9% (34/71) with 4 complete remissions (CR) and 30 partial remissions (PR). The median remission duration was 3.5 months. Particular drug activity was observed in the primary tumours, lymph nodes and pleural metastases. Toxicity (leukopenia, anaemia, vomiting, reversible rhythmic cardiac disorder, stomatitis) was mild, alopecia was registered less than in adriamycin medication. One fatal congestive heart failure occurred. The actual mean survival time calculated on the basis of the data gained from 64 patients was 7.0 months (range 2-22). The high antitumour activity and no increase in toxicity justify the incorporation of high dose epirubicin into combination therapy.
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PMID:Phase II study of 4'-epi-doxorubicin in patients with untreated, extensive small cell lung cancer. South-East European Oncology Group (SEEOG). 216 33

The results of radiotherapy alone for patients with locally advanced (stage III or IV) nasopharyngeal cancer (NPC) are poor in spite of the initial complete clearance. Twenty-seven patients (26 stage IV) were treated with concurrent standard radiotherapy and cisplatin 100 mg/m2 intravenously on day 1 and every 3 weeks for three courses. In 24 (89%) patients, complete response (CR) was achieved. The CR rate was higher for poorly undifferentiated cancer (100%). The major side effects were leukopenia (97%), anemia (54%), nausea and vomiting (81%), stomatitis (92%), and renal impairment (52%). Most of these side effects were either mild or moderate and reversible. All patients finished the radiotherapy dose (greater than 6,450 cGy), 19 (70%) had three courses of cisplatin, and eight had only two courses, six due to drug toxicity. Twenty-six patients with stage IV disease were compared with 78 patients treated with radiotherapy alone by the Radiation Therapy Oncology Group (RTOG). The disease-free survival (DFS), overall survival, and the incidence of distant organ metastasis appear to be better in the combined group. It was concluded that the combination of chemo-radiotherapy in patients with locally advanced NPC needs to be evaluated in a phase III randomized trial.
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PMID:Chemo-radiotherapy in patients with locally advanced nasopharyngeal carcinoma: a radiation therapy oncology group study. 219 21

Sixteen patients with metastatic carcinoma of the colon were treated with a regimen of leucovorin 200 mg/m2, given as a 10-min infusion followed by a median dose of 833 mg/m2 (range 500-1000 mg/m2) 5-fluorouracil every two weeks. For the 16 patients with proven metastatic disease, two-year survival exceeds 50%. Responses were: 2 complete; 4 partial; 4 minor; 3 progression; and 3 not evaluable but without progression to date. Toxicities include: 8 (50%) leukopenia; 9 (56%), 1 severe thrombocytopenia; 9 (56%), 2 severe, diarrhea; 9 (56%), 3 severe, nausea/vomiting; 8 (50%), 1 severe, stomatitis; 7 (44%) conjunctivitis; 6 (38%) alopecia; and 13 (81%), 3 severe, neurotoxicity. Leucovorin appears to exert a dose-dependent beneficial effect on both the response and survival produced by the intermittent high-dose 5-fluorouracil schedule. This benefit first appears to increase substantially when the leucovorin dose is increased from 120 to 200 mg/m2. Findings identify a testable candidate regimen for selected good risk patients. Full selection criteria remain to be identified.
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PMID:Dose-dependent leucovorin efficacy with an intermittent high-dose 5-fluorouracil schedule. 220 56

Six patients with advanced renal cell carcinoma was treated with a new chemo-endocrine regimen consisting of Tegafur, Adriamycin, Methotrexate and Tamoxifen. Estrogen receptor was measured in four cases from renal or metastatic tumors by DCC method, presenting 14.7, 9.7, 1.0 and 0 f moles/mg protein respectively. The patients were medicated with 800-1,200 mg of Tegafur and 20 mg of Tamoxifen daily po, and 20 mg of Adriamycin and 10 mg of Methotrexate intermittently for two weeks interval iv. According to a criteria of Japan Society for Cancer Therapy, two were regarded as CR, one as PR, one as NC and two as PD. The one out of two cases with and without estrogen receptor responded favourably to this therapy. Side effects observed in the treatment were mild gastrointestinal disorders including nausea and vomiting, slight degree of leukopenia, stomatitis, pigmentation and liver dysfunction. The patients were found to be in good quality of life during the treatment because of less toxicity. This therapy can be regarded as a good modality for a treatment of advanced renal cell carcinoma. This is a first report of combined chemo-endocrine therapy with Tegafur, Adriamycin, Methotrexate and Tamoxifen for renal cell carcinoma in the world.
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PMID:[A combined chemo-endocrine therapy with tegafur, adriamycin, methotrexate and tamoxifen for advanced renal cell carcinoma]. 223 Apr 47

Twenty-three patients were included in this prospective study about the safety and efficacy of oral low dose methotrexate (MTX) in the treatment of refractory rheumatoid arthritis. Patients received a mean dosage of 6.6 +/- 1.8 (SD) mg weekly over a mean duration of 16.6 +/- 12.5 months. Patients improved significantly in all clinical parameters of efficacy. There were significant reductions in Lansbury joint scores (p less than 0.001), duration of morning stiffness (p less than 0.001), sedimentation rates (p less than 0.001), C-reactive protein (p less than 0.01), IgG(p less than 0.01), rheumatoid factor (p less than 0.01) and significant increase in grip strength (p less than 0.001), hemoglobin (p less than 0.05) after 17 months of treatment with MTX. Radiographic progression of joint disease were assessed using global scoring method. The mean rate of development of erosions and joint-space narrowing during MTX therapy was significantly less than the rate of radiographic progression before MTX therapy (8.1 +/- 7. 9/year vs. 1.9 +/- 3.8; p less than 0.05). Adverse reactions during MTX therapy included transient transaminase elevation (17.4%). Five patients (21.7%) were withdrawn because of leukopenia (2), interstitial pneumonitis (1), stomatitis (1), skin rash (1). We conclude that low-dose methotrexate is effective for the management of clinical disease activity in patients with refractory rheumatoid arthritis and may be a disease-modifying anti-rheumatic drugs (DMAR-Ds) by roentgenographic criteria.
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PMID:[Low dose methotrexate therapy in rheumatoid arthritis]. 224 52


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