Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

23 patients with osteogenic sarcoma were observed during 142 6-hour high-dose infusions of methotrexate (MTX, 3,000--8,200 mg/m2). Calcium leukovorin was given by intravenous injection at 3-hour intervals beginning 2 h after the completion of each MTX infusion with extension of the intervals to 6 h following the first day of rescue. All patients also received continuous intravenous infusions of alkalinized fluids for the entire duration of leukovorin rescue. No larger doses of leukovorin were given to any patient. Three of the 142 MTX infusions resulted in mild cytotoxic side effects. Plasma MTX clearance ranged from 90 to 600 ml/min among the 62 infusions where plasma clearance could be accurately calculated. The 3 patients with mild toxicity had low drug clearance, but others with similar low MTX clearance experienced no apparent toxic effects beyond the expected transient nausea.
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PMID:High-dose methotrexate with a safe rescue program. 697 32

A phase III randomised study, comparing treatment with fluorouracil, epidoxorubicin and methotrexate (FEMTX) with the best supportive care, was conducted in patients with unresectable or metastatic gastric cancer. During the period from July 1986 to June 1992, 41 patients were randomised to receive FEMTX or best supportive care. MTX was given in a dose of 1500 mg m-2 intravenously (i.v.) followed after 1 h by 5-FU 1500 mg m-2 i.v. on day 1; leucovorin rescue was started after 24 h (30 mg orally every 6 h for 48 h) and epidoxorubicin 60 mg m-2 i.v. was administered on day 15. In addition both groups received tablets containing vitamins A and E. Response rates for FEMTX were as follows: complete response (CR), 19% (4/21); partial response (PR), 10% (2/21); no change (NC), 33% (7/21); and progressive disease (PD), 24% (5/21). Response rates in the control group were: NC, 20% (4/20); and PD, 80% (16/20). Increased pain was observed in one patient in the treated group and in 11 patients in the control group within the first 2 months. WHO grade III/IV toxicity in the chemotherapy group was as follows: nausea/vomiting 40%, diarrhoea 10%, stomatitis 15%, leucopenia 50% and thrombocytopenia 10%. One possible treatment-related death was due to sepsis. The median time to progression in the FEMTX group was 5.4 months [95% confidence interval (CI) 3.1-11.7 months], but only 1.7 months in the control group (95% CI 1.2-2.7 months) (P = 0.0013). Similarly, the FEMTX group displayed significantly (P = 0.0006) prolonged survival compared with the control group, i.e. median survival 12.3 months (95% CI 7.1-15.6 months) vs 3.1 months (95% CI 1.6-4.6 months). In conclusion, FEMTX combined with vitamin A and E is a fairly well-tolerated treatment, giving a response rate of 29% in patients with advanced gastric cancer, and also prolonging patients' survival. It can be used as a reference treatment in testing new investigational combinations.
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PMID:Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer. 753 17

The antigen reactive with murine monoclonal antibody (MAb) KS1/4 is expressed on epithelial malignancies and some normal epithelial tissues. Studies were undertaken to evaluate KS1/4-methotrexate (KS1/4-MTX) immunoconjugate in patients with advanced non-small cell carcinoma of the lung. Eleven patients in two different groups received KS1/4-MTX in two different escalating dose infusion schedules with a maximal tolerated dose of 1,750 mg/M2 and a cumulative dose of MTX of 40 mg/M2. Toxicities were similar in both groups and included fever, anorexia, nausea, vomiting, diarrhea, abdominal pain, guaiac positive stool, and hypoalbuminemia. Two patients had an associated aseptic meningitis. One patient had a 50% decrease in two lung nodules without a change in lymphangitic infiltrates. This patient received a second course of treatment and developed an immune complex-mediated arthritis and serum sickness. Four patients mounted a human antimouse antibody response. Post-treatment tumor biopsies documented binding of MAb KS1/4. These studies document the feasibility and potential usefulness of a MAb directed against tumor-associated antigens with the targeting of chemotherapeutic drugs in patients with non-small cell lung carcinoma.
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PMID:Monoclonal antibody KS1/4-methotrexate immunoconjugate studies in non-small cell lung carcinoma. 792 45

Sequential chemotherapy with methotrexate and 5-fluorouracil (MTX/5-FU) for advanced gastric cancer was given 29 patients. The procedure consisted of weekly MTX 100 mg/m2 (i.v.) followed three hours later by 5-FU 600 mg/m2 (i.v.) with leucovorin rescue on each of the following two days. Nine of 28 patients (32.1%) showed partial response to this treatment. Response rates were 28.6% in the 21 cases with poorly differentiated adenocarcinoma and 42.9% in the 7 cases with well- or moderately-differentiated adenocarcinoma. This procedure was especially effective for primary lesions (PR 9/20: 45%) and lymphnode metastases (CR 4 + PR 4, 8/17: 47.1%). Side effects were mild leukopenia and G-I symptoms such as nausea, diarrhea and loss of appetite, except in 1 patient who died of severe myelosuppression with sepsis. We concluded that sequential MTX/5-FU therapy is fairly effective and the adjuvant chemotherapy of choice for advanced or recurrent gastric cancer with not only poorly differentiated adenocarcinoma but also well- or moderately-differentiated adenocarcinoma.
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PMID:[Sequential chemotherapy with methotrexate and 5-fluorouracil for advanced gastric cancer]. 953 Mar 60

Osteosarcoma is one of the most common juvenile malignant tumors in Korea. Combined modality treatment (pre-operative chemotherapy + limb salvage surgery + adjuvant therapy) improved the patients' overall survival and quality of life. We evaluated the efficacy and feasibility of pre-operative chemotherapy with intra-arterial (IA) cisplatin plus continuous intravenous infusion (CI) of adriamycin. We assessed the rate of limb salvage, recurrence pattern and the survival impact based on the histologic response of pre-operative chemotherapy. Fourty-one patients with histologically-proven high grade osteosarcoma of the extremities were enrolled from January 1990 to June 1995. Pre-operative chemotherapy, cisplatin 120 mg/m2 IA and adriamycin 75 mg/m2/72 h CI was administered every 3 weeks for 3 cycles, followed by limb salvage surgery if possible or by amputation. According to the histologic tumor response, if the tumor necrosis was >90%, the same regimen was administered for 3 cycles as an adjuvant therapy. A salvage regimen (Ifosfamide 7.5 gm/m2/5 d IV + high dose MTX 10 gm/m2 IV+VP-16 360 mg/m2/3 d IV) was administered every 3 weeks for 6 cycles if the tumor necrosis was <90%. Of 41 patients, 37 patients were evaluable for efficacy and toxicities, because 4 patients refused chemotherapy after 1 or 2 cycles. Twenty-one patients were male and 16 were female with median age of 16 years (range 8-41). The tumor locations were: distal femur 20, proximal tibia 8, humerus 6, distal tibia 2 and 1 in proximal femur. All but one patient, who died of neutropenic sepsis, completed the planned pre-operative therapy. Of the 36 patients who received surgery, limb salvage surgery was possible in 30 patients (83.3%) and 27 patients (75%) showed a good response (grade III 10; 27.8%, grade IV 17; 47.2%). With a median follow-up of 23 months, 3-year disease-free survival rate was 54.7% and overall survival rate was 78.3%. Of the 15 patients who recurred, the major metastatic site was the lung. No operation-related mortality was observed. Most patients experienced grade III-IV nausea, vomiting and hematologic toxicities, which were reversible with supportive cares. Pre-operative chemotherapy with IA DDP+CI ADR followed by surgery showed 75% histologic tumor response rate, 83% limb salvage rate and 54.7% 3-year disease-free survival rate with tolerable side effects. To improve the survival rate, the possible role of good salvage chemotherapy with a non-cross resistance regimen in poor responders should be evaluated.
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PMID:Combined pre-operative chemotherapy with intra-arterial cisplatin and continuous intravenous adriamycin for high grade osteosarcoma. 1020 5

In a prospective multi-centre collaborative study, 516 patients with advanced cancer were treated by epirubicin (pararubicin, EPI) containing regimens. After CEOP (cyclophosphamide CTX, EPI, vincristine VCR and prednisone PDN) was used in the treatment of 213 patients with non-Hodgkin's lymphomas, 87 patients had complete remission (CR) and 99 partial remission (PR). Their response rate was 87.3%. However, there were 2 CR and 71 PR in 161 patients with non-small cell lung cancer treated by CEP regimen (CTX, EPI and cisplatin PDD), with a response rate of 45.3%. In 70 breast cancer patients treated by EMF regimen (EPI, Methotrexate MTX and 5-fluorouracil 5-FU), 8 had CR and 28 PR, with a response rate of 51.4%. The EPI containing regimens were also effective in dealing with gastro-intestinal tract and nasopharyngeal cancers. Adverse effects of epirubicin containing regimens were mainly nausea and vommiting, and the dose-qlimit toxicity was leucopenia. Hepatic, cardiac and renal toxicities were rather mild. The current phase III study revealed that the effect of epirubicin is similar to that of adriamycin, but the cardiac toxicity is relatively mild. So the effects can be improved by increasing the dose-intensity.
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PMID:[Epirubicin containing regimens in advanced malignant tumors report of 516 cases. Epirubicin Collaborative Study Group]. 1037 13

The efficiency and toxicity of treatment regimens for nonintensive cytoreduction in 57 outpatients with refractory acute leukemia (mean age 56 years, 51 AML, six ALL/AUL) were retrospectively studied. Seventeen patients received one treatment regimen, 19 patients two treatment regimens, and 21 patients three or more treatment regimens. The treatment regimens analyzed were 6-thioguanine p.o. (daily) (T), 6-thioguanine p.o. (4-7 days/week) + cytarabine s.c./i.v. (once a week) (T+C), 6-mercaptopurine p.o. (daily) (MP), 6-mercaptopurine p.o. (daily) + methotrexate p.o./i.v. (once a week) (MP+MTX), etoposide p.o. (daily) (E), and mitoxantrone i.v. (M). The median leukocyte count was higher for M (73 x 10(9)/l) than for the other treatment regimens (T: 27 x 10(9)/l, T+ C: 37 x 10(9)/l, MP: 24 x 10(9)/l, MP + MTX: 30 x 10(9)/l, E: 31 x 10(9)/l). A cytoreduction >50% in the peripheral blood was achieved by T in 11/19, by T+C in 7/11, by MP in 5/8, by MP+MTX in 3/6, by E in 3/4, and by M in 16/22 patients. The period of cytoreduction was regarded as the duration of response - T: median 53 days, range 5-98; T+C: median 61 days, range 14-226; MP: median 37 days, range 4-192; MP + MTX: median 58 days, range 36-59; E: median 121 days, range 26-159; M: median 39 days, range 8-78. T and T + C were well tolerated by all but three patients (stomatitis, diarrhea, WHO grade 2). MP was accompanied by a rise of transaminases (WHO 1-3) in 5/6 patients. E led to stomatitis (WHO 1,2) in 4/5 and M to nausea/vomiting (WHO 1,2) in 5/22 and to stomatitis (WHO 2) in 4/22 cases. The mean survival time after start of palliative cytoreduction was 16 weeks (2-65). In summary, 6-thioguanine +/- cytarabine was best tolerated with effective but in oral monotherapy - often protracted cytoreduction in 60% of patients. Mitoxantrone showed tolerable side effects and potent cytoreduction in 73% of patients even after ineffective palliative pretreatment. Palliative cytoreductive therapy does not reduce the quality of life and can prevent complications of significant leukocytosis in refractory acute leukemia.
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PMID:Palliative cytoreduction in refractory acute leukemia: a retrospective study of 57 adult patients. 1080 35

A 52-year-old woman was admitted to the gynecological department of our hospital on July 29, 2002 because of a right lower abdominal mass. She has been suffering from pain in the right leg and inguinal area for a month before coming to the hospital. She was found to have pancytopenia and high serum levels of LDH and IgD. A bone marrow examination showed 63.8% of plasma cells and serum immunoelectrophoresis showed M-protein of the IgD-lambda type. She was diagnosed as having multiple myeloma and transferred to our department. VAD therapy was started from August 22. Although the plasma cells in the bone marrow almost disappeared, the right lower abdominal mass remained and a new mass appeared on the right frontal chest wall after two courses of the treatment. Combination chemotherapy with vincristine, ranimustine, melphalan, and dexamethasone (ROAD) was started on November 1. This was followed with thalidomide and radiation therapy of the right inguinal region was added. On December 16th, she suddenly experienced speech disturbance, nausea and the disturbance of consciousness. Examination of her cerebrospinal fluid showed 368/microl mononuclear cells with 93% plasma cells. The plasma cells disappeared after the 6th intrathecal injection with MTX and prednisolone and the chemotherapy was resumed. One month later, CNS relapse was apparent followed by generalized spread of the tumor mass, and she died on March 17, 2003.
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PMID:[Multiple myeloma of the IgD-lambda type invading CNS]. 1555 49

Oral mucositis is a major toxicity associated with high-dose methotrexate (HD-MTX) therapy in the treatment of children with acute lymphoblastic leukaemia and osteosarcoma. This pilot matched case-control study investigated the associations between plasma concentration of MTX at 42 (p-MTX(42h)) and 66 (p-MTX(66h)) h, absolute neutrophil count (ANC) < or = or >1.0 x 10(9)/l, serum transaminases (ASAT/ALAT) < or > or =58 U/l, WHO < or > or =grade 2 nausea/vomiting and WHO < or > or =grade 2 oral mucositis. In this study, 11 children with WHO > or =grade 2 oral mucositis were compared with 17 control children matched for age, diagnosis and MTX-dosage. The results indicated that children with p-MTX(42h) > or = 1.0 micromol/l had an odds ratio (OR) of 4.3 of developing oral mucositis when compared with the referent group of children who had p-MTX(42h) < 1.0 micromol/l. Children with p-MTX(66h) >= 0.2 micromol/l had an OR of 8.2 of developing oral mucositis when compared with the referent group of children who had p-MTX(66h) < 0.2 micromol/l. Children with ANC < or = 1.0 x 10(9)/l had an OR of 1.2 of developing oral mucositis when compared with the referent group of children who had ANC > 1.0 x 10(9)/l. In comparison with the referent group of children, who had <58 U/l ASAT/ALAT, those with ASAT/ALAT > or = 58 U/l had an OR of 1.2 of developing oral mucositis. Finally, children with WHO grade > or =2 nausea/vomiting had an elevated risk of developing oral mucositis when compared with the referent group of children who had WHO grade <2 nausea/vomiting (OR = 8.7). In conclusion, the results in this preliminary study provide support for the hypothesis that the risk of oral mucositis is associated with the plasma MTX concentration at 66 h and the level of nausea/vomiting.
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PMID:Association of plasma methotrexate, neutropenia, hepatic dysfunction, nausea/vomiting and oral mucositis in children with cancer. 1841 35

This study aims to determine the prevalence of methotrexate-induced nausea and vomiting in both adolescent and adult patients with inflammatory arthritis. A survey of methotrexate side effects was conducted on patients with inflammatory arthritis. We provided a brief questionnaire to unselected patients with inflammatory arthritis being treated with methotrexate attending adolescent and adult rheumatology clinics. The questions related to the presence, absence, and severity of nausea and vomiting, the temporal relationship with methotrexate and whether anti-emetics had been prescribed. A total of 106 patients from the age of 13 years and above--57 adults (over 20 years) and 49 adolescents (13-19 years) were included in this study. The median age for those experiencing nausea was 19 years (interquartile range (IQR) 7) and for those with no nausea 55 years (IQR 46) (p < 0.001). Thirty-six out of 49 adolescent patients reported nausea (73%) compared to only 20/57 adults (35%) (p < 0.001). Multiple logistic regression analysis showed that the nausea group had a significantly higher proportion of adolescents (p = 0.0002), patients taking subcutaneous (SC) methotrexate MTX (p = 0.002), and patients with duration of MTX of more than 1 year (p = 0.049). Adolescents were estimated to have over 6 times higher odds of nausea compared to adults (OR 6.31, 95% CI 2.38 to 16.75, p = 0.0002) after adjusting for SC MTX and duration of MTX. Only 22% of adolescents and 10% of adults were prescribed anti-emetics. There is a higher prevalence of MTX-induced nausea and vomiting in adolescents and younger adult patients with inflammatory arthritis compared to older adults. The role of anti-emetics in the treatment of these symptoms is unclear.
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PMID:Methotrexate-induced nausea and vomiting in adolescent and young adult patients. 2410 4


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