Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In patients with refractory germ cell tumour who fail to achieve complete remission (CR) or which achieve CR but subsequently experience disease progression within 2 months of receiving cisplatin + vinblastine + bleomycin (PVB) the results of further treatment are poor. Similarly, third-line therapy after cisplatin with VP 16 salvage rarely produces clinically significant remission. From February 1983 to October 1984 we treated 53 patients with ifosfamide (1.2 g/m2 per day on days 1-5), VP 16 (75 mg/m2 per day on days 1-5), cisplatin (20 mg/m2 per day on days 1-5), and N-acetylcysteine (2.0 g p.o. every 6 h on days 1-7). This was repeated every 21 days for four to six cycles. One group of patients (group A, 20 pts) had achieved partial remission (PR) but still had nonresectable tumours after PVB therapy; a further group (group B, 4 pts) had achieved CR with PVB but then experienced disease progression within 2 months; the remaining patients (group C, 28 pts) had experienced disease progression after one or more salvage attempts, including therapy with cisplatin and VP 16. Of the original 53 patients, 51 were evaluable for response. Toxicity included moderate to severe myelosuppression in almost all patients, fever/sepsis in 8, creatinine greater than or equal to 6 mg% in 4, and hematuria in 4 patients. There were no drug-related deaths. CR was attained in 17/51 patients (34%), these being 8/20 in group A, 1/4 in group B, and 8/28 in group C, and 10 patients have remained in CR for periods ranging from over 1 month to over 17 months. PR was achieved in 20 patients (40%), but their median duration of remission was only 2 months. We feel these results, obtained in a poor-prognosis patient population, are sufficiently encouraging to warrant further study of this regimen, including investigation of its use as initial salvage therapy following PVB.
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PMID:VP 16 plus ifosfamide plus cisplatin as salvage therapy in refractory testicular cancer. 381 18

Diaziquone (AZQ), a new lipid-soluble antitumor agent, was given by 15-30-minute infusion on a daily X 5 schedule to 47 children with refractory solid tumors and leukemia. The starting daily dose of 6 mg/m2 was escalated to 10 and 35 mg/m2 in patients with solid tumors and leukemia, respectively. In patients with solid tumors, myelosuppression was dose-limiting at a daily dose of 10 mg/m2. In patients with leukemia, prolonged pancytopenia and bone marrow hypoplasia were observed at daily doses greater than or equal to 25 mg/m2. At these higher doses, significant hyperbilirubinemia associated with sepsis was also seen. Corresponding increases of transaminases or alkaline phosphatase and significant hemolysis were not noted. The maximum tolerated dose for this daily dose schedule was 9 mg/m2 in children with solid tumors and 25 mg/m2 in children with relapsed leukemia. Responses to AZQ included stabilization of disease in osteosarcoma, neurofibrosarcoma, pinealoma, and ependymoma. A patient with juvenile chronic myelocytic leukemia in blast crisis converted back to the chronic phase. A patient with acute lymphoblastic leukemia had a substantial decrease in cerebrospinal fluid blast count. Bone marrow aplasia was achieved in children with acute lymphoblastic leukemia and acute nonlymphoblastic leukemia; however, remissions were not achieved. A phase II study of AZQ in children with refractory malignancies is now being performed by the Childrens Cancer Study Group.
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PMID:Phase I clinical evaluation of diaziquone in childhood cancer. 385 80

Vindesine, etoposide (VePesid), and prednisolone (VEP) have been evaluated as a second-line combination regimen in 20 patients with grade II non-Hodgkin's lymphoma (NHL) who relapsed during or after first-line intensive therapy. The overall response rate was 40% (20% complete, of 9 to 13+ months' duration, and 20% partial, of 1.5 to 5 months' duration). The main toxicities were alopecia and myelosuppression (with two nonfatal cases of septicemia); nausea, vomiting, neurotoxicity, and skin and mucosal problems were relatively uncommon. VEP appears to be an active second-line regimen with acceptable toxicity in relapsed high-grade NHL patients.
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PMID:Vindesine, etoposide (VP-16), and prednisolone (VEP) in relapsed patients with grade II non-Hodgkin's lymphoma. 397 55

The M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) regimen was used to treat 25 patients with transitional cell carcinoma of the urothelial tract. Treatment consisted of monthly cycles of 30 mg. per m.2 methotrexate, followed 24 hours later by 3 mg. per m.2 vinblastine, 30 mg. per m.2 doxorubicin and 70 mg. per m.2 cisplatin, and concluded with repeat vinblastine and methotrexate on days 15 and 22. Significant tumor regression was noted in 71 per cent of the patients. Complete clinical remission was observed in 12 of 24 patients (50 per cent, 95 per cent confidence limits 30 to 70 per cent) with bidimensionally measurable indicator lesions, 6 of whom had pathological confirmation. After surgical exploration 4 patients required downstaging to a partial remission. The median duration of response has not yet been reached at 9.5 plus months, range 4.5 plus to 16 plus. Five patients (21 per cent) had a partial clinical remission for 4 to 8 plus months, 1 had a minor response for 4 months and 1 had stable disease for 11 months. All metastatic sites responded, including bone (6 of 8 cases), liver (3 of 5), locoregional (12 of 17) and intravesical (6 of 7) disease. Toxicity included moderately severe myelosuppression that resulted in nadir sepsis in 4 patients and a drug-related death in 1, mild to moderate anorexia, vomiting, alopecia and renal dysfunction. These preliminary results suggest that treatment with methotrexate, vinblastine, doxorubicin and cisplatin is extremely effective against locoregional and disseminated urothelial tract tumors, with the expectation (95 per cent confidence limits) of inducing objective tumor regression in 53 to 89 per cent of the cases.
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PMID:Preliminary results of M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for transitional cell carcinoma of the urothelium. 403 49

Cisplatin plus 5-FU appears to have significant additive activity in various tumors, such as head and neck carcinoma and esophageal cancer. A partial explanation for this may be drug synergism, which has been noted in the L1210 leukemia model. Based on these data, a prospective trial of weekly bolus 5-FU (15 mg/kg) and cisplatin (60 mg/m2) given every 3 weeks was initiated at Indiana University. Forty-one patients, of whom 38 are fully evaluable for response, were treated with these two drugs. Ten partial and one complete response (complete + partial response rate = 29%) were observed in the 38 evaluable patients. Thirteen additional patients had stable disease for greater than or equal to 3 months. The median durations of remission and survival time were 6 and 10.3 months, respectively. Myelosuppression was unusually severe, with granulocyte counts less than 1000/mm3 in 65% of patients, including four patients with granulocyte count nadirs less than 100/mm3. Three patients developed granulocytopenic fever, with two drug-related deaths (sepsis, hyperosmolar coma). Nearly all patients had nausea and vomiting, but this was not a treatment-limiting toxic effect in any patient. Although this combination suggests a higher response rate than usually seen with bolus iv 5-FU in colon cancer, a trial comparing 5-FU alone or with cisplatin to determine whether true synergy exists is currently underway.
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PMID:Cisplatin plus 5-FU for the treatment of adenocarcinoma of the colon. 407 11

Analysis of the remission induction phase in three Medical Research Council trials of treatment of acute lymphoblastic leukaemia has provided evidence of the adverse effect of the combination of colaspase (L-asparaginase) with vincristine and prednisolone. Significant myelosuppression, particularly of the granulocytic series, resulted in an increase in Gram-negative sepsis and death during the neutropenic phase induced by colaspase. The rate of blast-cell regression was increased by colaspase. It is suggested that the introduction of colaspase should be delayed until there is evidence of bone marrow regeneration in order to procure this benefit without the attendant toxicity.
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PMID:Myelosuppressive effect of colaspase (L-asparaginase) in initial treatment of acute lymphoblastic leukaemia. 460 4

Forty-two patients with advanced testis carcinoma without previous chemotherapy were treated with VAB-4, and 41 were evaluable. The program consisted of three in-hospital inductions 16 weeks apart, and outpatient treatments every three weeks. Of the patients, 80% achieved complete remissions (CR). Chemotherapy alone induced CR in 61%, partial remissions (PR), in 24% and minor response (MR), in 15%. An additional 20% of patients (six PRs and 2 MRs) achieved CR following resection of residual tumor deposits. With a median follow-up of 27 months, the median duration of CR has not been reached. Of those achieving CR to chemotherapy alone, 12% had relapses. Bulk and extent of metastatic disease, histology of primary tumor, and tumor markers at the beginning of therapy influenced the frequency of CR. Of those with minimal disease, 90% achieved CR. The CR rate was 67% for those with advanced thoracic disease and 29% for those with advanced abdominal disease. Patients who had embryonal carcinoma and those who had no elevation of alpha-fetoprotein had a higher frequency of CRs. Myelosuppression with a leukocyte count drop less than 1000/mm3 occurred in three patients, and no patient had chronic renal failure or pulmonary fibrosis. One patient died from sepsis while in complete remission.
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PMID:VAB-4 combination chemotherapy in the treatment of metastatic testis tumors. 616 66

Forty-six patients with epidermoid carcinoma of the esophagus have been treated with a three-drug combination of cisplatin, vindesine, and bleomycin. Of the 40 patients currently evaluable for response, 21 have had partial remissions (52%). At least four of these responses were almost complete, with only microscopic disease found on endoscopy or review of the resected specimen. Toxic effects have, in general, been manageable. The major toxic effects included nausea and vomiting, nephrotoxicity, and myelosuppression. There were two drug-related deaths: one due to renal failure and one due to sepsis. The three-drug combination appears to be substantially more effective than either the two-drug combination of cisplatin and bleomycin or vindesine alone. Effects on survival cannot yet be evaluated.
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PMID:Cisplatin, vindesine, and bleomycin (DVB) combination chemotherapy for esophageal carcinoma. 616 70

Eleven patients with recurrent malignant glioma were treated with single high doses of BCNU ranging from 600 to 1400 mg/sq m. To prevent the characteristic late myelosuppression observed after conventional doses of BCNU, autologous bone marrow harvested just before drug treatment was infused 24 to 36 hours after therapy. Higher doses of BCNU causes earlier and more profound myelosuppression; one patient died on pancytopenia, breakdown of the gut epithelium, and Clostridium septicemia 10 days after receiving 1400 mg/sq m of BCNU. All patients experienced transient emesis; four developed transient elevation of hepatic enzymes, two reversible interstitial pulmonary infiltrates, and two who received 1400 mg/sq m BCNU suffered irreversible cortical damage. Eight patients receiving 600 to 1200 mg/sq m demonstrated reconstitution of polymorphonuclear leukocytes an platelets within at least 30 days after treatment. With a follow-up time of up to 19 months, four patients improved, three stabilized, and three deteriorated and died. The median survival time was 7 months. Computerized tomography performed on patients receiving constant corticosteroids showed diminished contrast enhancement and mass effect in eight patients. High-dose BCNU at doses up to 1200 mg/sq m with marrow rescue is a feasible approach to the treatment of patients with glioblastoma.
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PMID:High-dose BCNU with autologous bone marrow rescue for recurrent glioblastoma multiforme. 625

The development of drug resistance limits the survival or patients with small cell anaplastic carcinoma of the lung (SCLC). The present study was undertaken to overcome this problem by administering two alternating noncross resistant combination chemotherapy regimens. One-hundred-one patients were entered on study, and 98 were evaluable, with a median onstudy time of 55+ weeks. All patients received the initial combination therapy of cyclophosphamide, methotrexate, and vincristine, alternating every three weeks with Adriamycin and VP16-213 (etoposide). Radiation therapy was not a standard part of protocol. Thirty-two patients had regional disease (LD), and 66 had extensive disease (ED). Overall, 76% of patients responded to this therapy with 30 (31%) complete remission (CR) and 44 (45%) partial remissions (PR); the respective CR and PR rates were 31% and 50% for LD, and 30% and 42% for ED patients. Myelosuppression was the principal toxicity with a leukocyte nadir of 2.0 X 10(9)/1 in 10% of cycles. Septicemia in six neutropenic ED patients with progressive disease contributed to the only treatment-related deaths. Patients entering CR had a median survival greater than 51 weeks (range, 8-150+); 58+ for LD and 49+ for ED patients. Patients in PR had respective median survivals of 33+ (overall), 43+ (LD), and 24+ (ED) weeks. Forty patients have had relapses with initial sites being local sites in 35%, and neurologic in 38%. Although this protocol has not discernibly delayed the onset of drug resistance, the problem should be considered when new protocols are designed in SCLC.
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PMID:Alternating non-cross-resistant combination chemotherapy for small cell anaplastic carcinoma of the lung. 628 Aug 40


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