Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten previously untreated patients with gastric cancer were treated with etoposide, 120 mg/m2 intravenously (i.v.) on days 4, 5, and 6, Adriamycin, 20 mg/m2 i.v. on days 1 and 7, and cisplatin, 40 mg/m2 i.v. on days 2 and 8 (EAP). Etoposide, 240 mg/m2 on days 4, 5, and 6, was administered orally instead of intravenously in alternating cycles, and pharmacokinetic studies were performed in those who had previously undergone gastrectomy or who had tumor infiltrating the stomach to determine oral bioavailability. Nine patients had advanced measurable gastric cancer, and one patient had an elevated carcinoembryonic antigen after surgery for synchronous gastric and colon cancer. The median age was 54 years (range 38-69), and the median Eastern Cooperative Oncology Group (ECOG) performance status was 2 (range 0-3). Nine of 10 patients had poorly differentiated adenocarcinoma. Twenty-four cycles were administered to 10 patients, and hematologic data were available for 23 courses. ECOG grade 4 neutropenia and thrombocytopenia developed in 19 (83%) and 8 (53%) courses, respectively. Thirteen courses (54%) were complicated by fever requiring parenteral antibiotics. Two patients (20%) died due to neutropenic sepsis. The profound myelotoxicity observed in our study prompted us to terminate the investigation prior to completing accrual. The oral bioavailability of etoposide was 21% and 36% in the two patients who had had prior gastrectomy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase II trial of etoposide, doxorubicin (Adriamycin), and cisplatin (EAP regimen) in advanced gastric cancer. 222 Jun 57

A phase I trial of vincristine and etoposide was designed following the identification of a potentially synergistic antitumor effect in a murine model. The dose of vincristine was fixed (0.5 mg daily for 3 days). Etoposide was given at 1 of 3 total dose levels (250, 500, or 750 mg/m2) per treatment. Each dose was given in 3 equal fractions and each fraction was given daily for 3 days, i.e., 83.3 mg/m2/d x 3d, 166.7 mg/m2/d x 3d, or 250 mg/m2/d x 3d. A total of 31 patients were entered into study including 10, 18, and 3 patients treated at the 250, 500, and 750 mg/m2 dose levels, respectively. Dose-limiting toxicity occurred at the 750 mg/m2 level, in which Grade 4 myelosuppression developed in all of the patients. Life-threatening gram negative sepsis occurred in two of these patients and both required platelet transfusions. Grade 3-4 WBC toxicity was observed in 9 of 16 (56%) evaluable patients treated at the 500 mg/m2 level, but reversal of toxicity was generally rapid with repeat courses given at 3 week intervals in most patients. Non-hematologic toxicity was negligible. Objective responses were observed in 2 of 4 patients with Hodgkin's disease. The starting dose of etoposide recommended for phase II trials of this agent in combination with vincristine is 500 mg/m2; dose escalation may be possible in some patients.
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PMID:Phase I study of vincristine and escalating doses of etoposide. 279 73

The purpose of this study was to determine activity of etoposide-platin combination chemotherapy for chemorefractory gestational trophoblastic disease. A retrospective review of patients treated with etoposide-platin chemotherapy for chemorefractory trophoblastic disease was conducted. Patients received etoposide 100 mg/m2 and cisplatin 20 mg/m2 on Days 1 through 5 of 14- to 21-day cycles. Patient characteristics, responses, and toxicity were recorded. Seven women received etoposide-platin for chemorefractory disease. The median WHO prognostic index score upon initiation of therapy was 16 (range, 10-20) and patients had received a median 6 cycles of prior combination chemotherapy. Five patients developed grade IV neutropenia, four developed neutropenic sepsis, and two required platelet transfusions. Two patients developed significant deterioration of renal function. Six (86%) patients had complete responses, with normalization of hCG values, but only three (43%) patients with low pretherapy hCG levels have had sustained remissions. Etoposide-platin chemotherapy is an active regimen for the treatment of women with chemorefractory gestational trophoblastic disease but has significant hematologic and renal toxicity when used as salvage therapy. Future studies should investigate the incorporation of etoposide-platin into initial therapy of women with high-risk disease.
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PMID:Etoposide-platin combination therapy for chemorefractory gestational trophoblastic disease. 770 78

Cisplatin and carboplatin are platinum-based chemotherapeutic agents with broad antitumor activity and significantly different toxicity profiles. They are commonly used in combination with etoposide (VP-16) in chemotherapeutic regimens. We conducted a phase I trial using the combination of cisplatin, carboplatin, and etoposide in advanced malignancy, aimed at delivering a higher dose intensity of active platinum species while taking advantage of their nonoverlapping toxicities. Etoposide was added because of its synergistic action with platinum compounds. The initial chemotherapy regimen consisted of carboplatin 180 mg/m2 on day 1, cisplatin 70 mg/m2 on day 1, and etoposide 60 mg/m2 on days 1-3. Dose was escalated based on toxicity observed at each level and separately for patients with a previous history of chemotherapy and for those with no prior treatment. Thirty-six patients were entered in the study, and 33 were evaluable. Hematologic toxicity was dose limiting. Grade 3-4 leukopenia was noted in 22 of 33 (66%) patients and grade 3-4 thrombocytopenia was noted in 16 of 33 (48%). No serious bleeding complications occurred. There was one treatment-related death due to neutropenic sepsis. Nonhematologic toxicity was mild and not dose limiting. Ototoxicity and nephrotoxicity were minimal. No complete responses (CR) occurred. Nine of 33 (27%) patients had objective responses, including 3 patients with adenocarcinoma of the esophagus or gastroesophageal junction who had failed prior chemotherapy. Fifteen of 33 (45%) patients had stable disease. The maximum tolerated dose varied for patients who had received prior chemotherapy and for those who were previously untreated. For further studies, the recommended dosing for previously untreated patients is carboplatin 300 mg/m2 on day 1, cisplatin 70 mg/m2 on day 1, and etoposide 105 mg/m2 on days 1-3. The recommended dosing for patients with a history of prior chemotherapy is carboplatin 220 mg/m2 on day 1, cisplatin 70 mg/m2 on day 1, and etoposide 75 mg/m2 on days 1-3. The combination of cisplatin, carboplatin, and etoposide merits further testing in phase II trials.
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PMID:Combination chemotherapy with cisplatin, carboplatin, and etoposide in advanced malignancy: a phase I trial. 934 36

Extranodal natural killer (NK)/T-cell lymphoma, nasal type, and aggressive NK-cell leukemia are rare, and their standard therapy has not been established. They are Epstein-Barr virus-associated lymphoid malignancies, and tumor cells express P-glycoprotein leading to multidrug resistance of the disease. Patients with stage IV, relapsed or refractory diseases have a dismal prognosis, with survival measured in months only. To develop an efficacious chemotherapeutic regimen, we conducted a dose-escalation feasibility study of a new chemotherapeutic regimen, SMILE, comprising the steroid dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide. The components of SMILE are multidrug resistance-unrelated agents and etoposide. Etoposide shows both in vitro and in vivo efficacy for Epstein-Barr virus-associated lymphoproliferative disorders. Eligible patients had newly diagnosed stage IV, relapsed or refractory diseases after first-line chemotherapy, were 15-69 years of age, and had satisfactory performance scores (0-2). Four dose levels of methotrexate and etoposide were originally planned to be evaluated. At level 1, six patients with extranodal NK/T-cell lymphoma, nasal type, were enrolled. Their disease status was newly diagnosed stage IV (n = 3), first relapse (n = 2), and primary refractory (n = 1). All of the first three patients developed dose-limiting toxicities, and one of them died of sepsis with grade 4 neutropenia. A protocol revision stipulating early granulocyte colony-stimulating factor administration was made. Two out of three additional patients developed dose-limiting toxicities that were all manageable and transient. For the six enrolled patients, the overall response rate was 67% and the complete response rate was 50%. Although its safety and efficacy require further evaluation, we recommend a SMILE chemotherapy dose level of 1 for further clinical studies.
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PMID:Phase I study of dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy for advanced-stage, relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma and leukemia. 1829 94