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)

Trimetrexate (TMTX), a potent inhibitor of the enzyme dihydrofolate reductase, was shown to be more active than its analogue, Methotrexate, against murine and human tumor cell lines in vitro and in vivo. We conducted two sequential phase I studies using a single bolus injection of TMTX every 14 days (Schedule A) and a weekly x 3 schedule every 4-6 weeks (Schedule B). Twenty-seven patients were treated on Schedule A with a TMTX dose range of 5 mg/m2 to 450 mg/m2 and 23 patients were treated on Schedule B with a TMTX dose range of 50 mg/m2 to 200 mg/m2. The dose limiting toxicity was myelosuppression on both schedules. The development of hematological toxicity was highly variable at different dose levels and within the same patient at a particular dose level. The nadir of blood counts was reached by Day 8 to 10 on the single dose schedule with recovery by Day 14. On Schedule B, the nadir granulocyte count occurred on Day 14 while platelet count was generally lowest by Day 20; the blood counts usually recovered 7 to 10 days after the last dose. Other common side-effects includes skin toxicity and stomatitis which were worse on the weekly schedule. Less common toxicities included mild nausea and vomiting, diarrhea, and transient deterioration in renal and hepatic functions. The occurrence of toxicity was not related to the extent of prior treatment, liver metastases, or accumulation of third space fluids. Based on our results, we recommend a starting TMTX dose for Phase II studies of 200 mg/m2 every 2 weeks or 100 mg/m2 to 125 mg/m2 on the weekly schedule.
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PMID:Phase I studies of trimetrexate using single and weekly dose schedules. 183 42

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

Trimetrexate (TMTX) is a potent inhibitor of dihydrofolate reductase that circumvents the transport resistance seen with methotrexate and has a wide spectrum of preclinical activity. A total of 18 patients with advanced cancer were treated in a clinical and pharmacological phase I trial with TMTX given as a continuous 5-day intravenous infusion. Neutropenia, thrombocytopenia and stomatitis were the dose-limiting toxicities at the maximum tolerated dose of 50 mg/m2 per 120 h (10 mg/m2 per day for 5 days). There was one septic death associated with neutropenia. Other toxicities were mild rash, mild nausea and transiently raised serum transminase levels. Significant relationships between the dose given and the AUC of plasma TMTX and the steady-state plasma level were established. Significant, although weak, relationships between the percentage of change in neutrophils and platelets and both the AUC and steady-state plasma level of TMTX were also observed. No objective tumour responses were seen, although six patients had stable disease. The recommended phase II dose for a continuous infusion of trimetrexate is 40 mg/m2 per 120 h.
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PMID:A phase I study of trimetrexate (NSC 352122) administered by 5-day continuous intravenous infusion. 252 92

Trimetrexate is a nonclassical folate antagonist. It was evaluated in 43 patients, previously not exposed to chemotherapy, with incurable and/or demonstrated progression of squamous cell head and neck cancer following surgery and/or radiotherapy. Trimetrexate was initially administered at 8 mg/m2 intravenous (IV) daily for 5 days, repeated every 3 to 4 weeks with dose adjustments depending on patient tolerance. Thirty-eight of the 43 patients entered in this study were evaluable for response. The 28 males and 10 females had a median age of 60 years. Their median performance status on the Zubrod scale was 1. Thirty-seven patients (97%) had received prior radiotherapy. The disease had metastasized in 84% of the patients with dissemination primarily to the subcutaneous soft tissue (40%). Ten patients (26%; with a 95% confidence interval of 12% to 40%) achieved a partial response (PR) with a median duration of 12.2 weeks (median time to PR was 3.2 weeks). The median survival of the 43 patients was 17.3 weeks with 10 patients alive at last follow-up. Hematologic grade 3 to 4 toxicities included leukopenia (19%), thrombocytopenia (9%), and granulocytopenia (5%). Nonhematologic grade 3 to 4 toxicities possibly attributable to trimetrexate treatment included stomatitis (7%).
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PMID:Trimetrexate as a single agent in patients with advanced head and neck cancer. 296 82

Trimetrexate (TMQ; NSC 352122) is a potent inhibitor of dihydrofolate reductase with good activity against murine i.p.-implanted B16 melanoma and colon 26 tumors. Preclinical antineoplastic activity, demonstrated schedule dependency, and data suggesting effectiveness against methotrexate-resistant cells prompted a Phase I clinical and pharmacokinetic study of trimetrexate using an i.v. daily x5 schedule. Forty-three good performance status patients were treated with 12 dose levels using daily doses varying from 0.5 to 15 mg/m2/d. Plasma and urine samples were obtained for pharmacokinetic analysis using a high-performance liquid chromatographic method. Myelosuppression was dose limiting and 15 mg/m2/d x5 was the maximum tolerated dose. White blood cell (WBC) and platelet toxicity were noted at doses of 1.6 mg/m2 and above. Median WBC and platelet nadirs occurred on approximately Days 11-12 with recovery by Days 15-18. Nonhematological toxicity included mucositis, nausea and vomiting, stomatitis, diarrhea, and rash. Evidence for antitumor activity was seen in seven patients. Trimetrexate elimination from plasma could be represented as either a bi- or triexponential process. Terminal elimination half-lives were in the range of 5-14 h in patients represented by a triexponential model. Approximately 10-20% of the dose administered was excreted in urine over a 24-h period. The recommended starting dose for patients in Phase II trials using the d x5 i.v. schedule is 8.0 mg/m2/d repeated every 21 days. Dose escalations may be possible depending on the extent of prior therapy and individual tolerance of the drug.
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PMID:Phase I clinical and pharmacokinetic study of trimetrexate using a daily x5 schedule. 297 Feb 94

Oncology nurses play a critical role in the detection and management of adverse effects resulting from the toxicity of colorectal cancer (CRC) treatment regimens. Standard chemotherapy for CRC involves combination 5-fluorouracil plus leucovorin, a regimen with a well-characterized toxicity profile that includes abdominal cramping and diarrhea, nausea and vomiting, skin and hypersensitivity reactions, fatigue, stomatitis, neutropenia and thrombocytopenia, and alopecia. Diarrhea is the principal dose-limiting toxicity. Trimetrexate, a nonclassical antifolate, is currently being investigated in combination with 5-fluorouracil/leucovorin in phase II/III trials. In addition to the management of side effects, the psychosocial and educational needs of CRC patients require attention. The rigorous treatment schedule presents patients with multiple obstacles in daily living, significantly impacting their quality of life. The oncology nurse is vital in managing the care of CRC patients and ensuring that their physical, psychosocial, and educational needs are met. Educating patients about adverse treatment effects empowers them to manage their symptoms and enables them to alleviate serious or life-threatening treatment complications. Three case studies are provided to illustrate and reinforce nursing management strategies for hypersensitivity reactions, fatigue, and psychosocial issues related to CRC treatment.
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PMID:Nursing care strategies for the management of side effects in patients treated for colorectal cancer. 942 23