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)

Thirty-five patients with solid tumors received 44 courses of bis-chlorethylnitrosourea (BCNU) at doses ranging between 600 and 1,400 mg/m2 with cryopreserved or fresh autologous bone-marrow support. Eight patients treated at 600 mg/m2 received no bone-marrow support for their first course of BCNU. Maximum follow-up was 25 months (median, four months). Myelosuppression was severe and dose related but was less prolonged in the marrow-supported groups (p = 0.01) and was not dose limiting. Myelosuppression-related toxicity of infection and hemorrhage occurred in 21 (47%) of 44 courses of treatment. Pulmonary toxicity occurred in seven of 35 patients; abnormal liver function occurred in 18 of 30 patients greater than one month from treatment; and central nervous system symptoms that may have been drug related occurred in six of 35 patients. There was no renal or cardiac toxicity. Except for myelosuppression, toxicity was not dose related. Treatment-related deaths included four with pulmonary toxicity, two with liver toxicity, sepsis in four, and gastrointestinal tract toxicity in one patient. We conclude that the limiting side effect of high-dose BCNU (greater than or equal to 600 mg/m2) is visceral toxicity; the extent of myelosuppression is shortened by the infusion of bone marrow, whether cryopreserved or fresh; and marked tumor regression can be achieved with high-dose BCNU.
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PMID:Autologous bone-marrow transplantation: host effects of high-dose BCNU. 636 27

Thirty-two patients with refractory non-Hodgkin's lymphoma were treated with high-dose cytosine arabinoside (ara-C) given at 2 g/m2 IV over three hours every 12 hours for 4-8 g/m2/course repeated at three to four week intervals. There were eight partial responses (29%) and two minor responses among 28 evaluable patients. The median response duration was 10 weeks (range, 6-33 weeks). The median survival was significantly prolonged in responders compared to nonresponders (28 versus 15 weeks; p = 0.03). Two additional patients treated with 12 g/m2/course died of sepsis and myelosuppression. The dose-limiting toxicity was myelosuppression, which was more pronounced in patients with prior extensive radiation therapy and bone marrow involvement. In vivo measurements of intracellular concentrations of ara-CTP, the active metabolite of ara-C, showed significantly higher values in bone marrows with lymphomatous involvement compared to normal bone marrows (210 versus 95 microM; p = 0.05), probably indicating a preferential formation and retention of ara-CTP in malignant cells compared to normal hemopoietic cells. In addition, higher ara-CTP levels were found in bone marrows that had higher percentages of cells in S phase.
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PMID:High-dose cytosine arabinoside in non-Hodgkin's lymphoma. 636 30

Thirty patients with advanced acute leukemia and lymphoma were treated with the sequential combination of high dose ARA-C (HiDAC 3 gm/m2 infused i.v. over 3 h at 0, 12, 24, 36 h) and asparaginase (ASP 6.000 IU/m2 i.m. at hour 42). The sequence was given on day 1 and 8 irrespective of the degree of myelosuppression. Of 22 patients with leukemia there was only one who was absolutely refractory to therapy. Complete remission was induced in 3 patients with ANLL (30%) and in 3 with ALL (30%). Three patients became hypoplastic but recovered with blasts and 12 died from infection, complicated by intracranial hemorrhage in 3, during hypoplasia. Of 8 patients with lymphoma, 2 were clearly refractory to therapy, one died from sepsis and the remaining 5 all entered remission (2 CR + 3 PR, 62%). Activity of HiDAC/ASP against CNS disease is suggested by the clinical response seen in patients with overt meningeal or intracerebral involvement. Toxicity associated with HiDAC/ASP was mainly hematologic. All but one patient experienced hypoplasia and severe pancytopenia; documented infections and major hemorrhages occurred in 80 and 20% of patients respectively. We conclude that HiDAC/ASP is a regimen with definite activity against acute leukemia and lymphoma including CNS disease. Alternate treatment schedules should be explored in order to reduce marrow toxicity.
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PMID:Sequential combination of high dose ARA-C (HiDAC) and asparaginase (ASP) for the treatment of advanced acute leukemia and lymphoma. 647 2

Twenty-eight patients with measurable or evaluable, regionally advanced or metastatic head and neck cancer received the combination of cyclophosphamide (C), adriamycin (ADR), and a 24-hour infusion of cis-diamminedichloroplatinum (II) (P). Most patients had received extensive prior surgery and radiation therapy, but only two had prior chemotherapy. We observed a 46% response rate (13/28) which included five complete responders and eight partial responders. Nine of the 13 patients responded within the initial month of treatment. The median response duration for the 13 responding patients was 7.5 months. Moderate to severe nausea and vomiting, and alopecia were the most significant toxicities. Myelosuppression (WBC less than 4,100 cells/mm3) occurred in 90% of patients but there were no episodes of sepsis, nor did we detect any meaningful impairment in renal function.
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PMID:Cyclophosphamide, adriamycin, and 24-hour infusion of cis-diamminedichloroplatinum (II) in the management of patients with advanced head and neck neoplasms. 653 49

A new treatment program was developed in an attempt to increase the complete remission rate and survival of previously untreated patients with advanced stages of diffuse aggressive lymphomas. A flexible number of cycles of ProMACE chemotherapy (prednisone, methotrexate, doxorubicin, cyclophosphamide, and epipodophyllotoxin VP-16) was alternated with a flexible number of cycles of MOPP chemotherapy (mechlorethamine, vincristine sulfate, procarbazine, and prednisone), and finally late intensification with ProMACE therapy was given. The duration of each phase of treatment was determined by the patient's rate of tumor response. Complete remissions were achieved in 55 of 74 patients (74%) with a median duration of follow-up exceeding 2 1/2 years. Only ten of the complete responders (18%) have had relapse. The dose-limiting toxicity is myelosuppression, and eight patients (10%) died from sepsis. Median survival for all patients has not been reached but is predicted to exceed 4 years with 65% of patients alive at 4 years. Previously we achieved a 46% complete remission rate with 38% of all patients alive at 4 years; relapse-free survival beyond 2 years was tantamount to cure. Therefore, ProMACE-MOPP chemotherapy represents a substantial improvement in treating patients with diffuse aggressive lymphomas.
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PMID:Diffuse aggressive lymphomas: increased survival after alternating flexible sequences of proMACE and MOPP chemotherapy. 660 Sep 2

Thirty-two patients with advanced gynecologic malignancies were treated with m-AMSA, 120 mg/m2 intravenously every 3 weeks. Seventeen patients with advanced carcinoma of the cervix who were treated with m-AMSA had a median performance status (CALGB scale) of 2. There were two partial responses (PR) (14%) in 16 evaluable patients. The median duration of survival was 76 days following the initiation of m-AMSA treatment. In ovarian carcinoma, none of the nine evaluable patients who were treated responded. One PR occurred among four treated patients with endometrial adenocarcinoma. Toxicity was limited to myelosuppression (WBC greater than 2500/micrograms in 29/77 courses, WBC greater than 1500/micrograms in 16/77 courses, platelets greater than 100,000/micrograms in 10/77 courses, and drug-induced anemia in 7/77 courses) and mild to moderate nausea and vomiting (10/31 patients). Three patients required hospitalization for fever and granulocytopenia, and one patient died from drug-induced sepsis. Although toxicity was acceptable in this group of heavily pretreated patients, m-AMSA has limited activity in patients with advanced carcinoma of the cervix and no apparent activity in patients with advanced epithelial ovarian carcinomas. Continued trials are indicated in patients with adenocarcinoma of the endometrium.
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PMID:A phase II trial of m-AMSA in the treatment of advanced gynecologic malignancies. 689 60

Fifty-one patients with metastatic non-small-cell lung cancer (NSCLC) were treated with VP-16-213 (4'-demethylepipodophyllotoxin) during a phase II trial. Of the 49 patients who had adequate trials, 2 patients achieved a partial response (PR), for an overall 4% major response rate. The median Karnofsky performance status (PS) was 80%; 85.7% of patients had adenocarcinoma and 14.2% had epidermoid carcinoma. Prior treatment with chemotherapy may have adversely affected response rate; the two responses occurred among the 25 previously untreated patients, while no responses were seen in patients who had previously received chemotherapy. Myelosuppression was the most frequent side effect and two drug-related deaths due to septicemia occurred. Other toxic effects noted included anorexia, nausea and hypotension during drug infusion. We conclude that VP-16-213 has minimal activity as a single agent in NSCLC.
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PMID:Phase II trial of VP-16-213 in non-small-cell lung cancer. 708 Nov 37

After perioperative adjuvant chemotherapy of a sigma-adenocarcinoma with 400 mg peptichemio and 500 mg 5-fluorouracil a 61-year-old woman developed a severe intoxication: myelosuppression with pancytopenia, gastroenteritis and ulcerative proctitis, toxic hepato- and myocardiopathy, impaired renal function and alopecia. As a result of reduced resistance pneumonias, urinary tract infection, sepsis, cytomegaly infection and candidiasis of the oral mucosa occurred. The toxic effects are attributed mainly to the high dose of peptichemio.
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PMID:[Severe intoxication after combined chemotherapy of a sigma-adenocarcinoma with peptichemio and 5-fluorouracil (author's transl)]. 711 29

Twenty-three pediatric cancer patients developed Pseudomonas aeruginosa septicemia during an 11-year period. Typically the patients had advanced neoplasia and were receiving immunosuppressive therapy. Severe myelosuppression was almost always present and antibiotic therapy during the prior 2-week period for proven or suspected sepsis was common. Disruption of the skin and mucosa in the anogenital regions was evident in the majority of patients, and the gastrointestinal tract represented the most common portal of entry. Patients who developed sepsis while relapsed had the highest case-fatality rate, and use of synergistic antibiotic combinations did not affect outcome in this group.
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PMID:Pseudomonas aeruginosa septicemia in childhood cancer patients. 717 13

Since October 1978, 25 patients with metastatic carcinoma of the bladder have been treated with cis-platinum, doxorubicin hydrochloride and cyclophosphamide. Patient selection for this protocol was relatively strict and included only patients who had measurable parameters. All 3 drugs (60 mg./m.2 cis-platinum, 40 mg./m.2 doxorubicin hydrochloride and 400 mg./m.2 cyclophosphamide) were given as a single dose every 4 weeks. Over-all, 19 of the 23 evaluable patients (82 per cent) responded to therapy. There were 5 complete drug-induced remissions and 14 partial remissions. Generally, the treatment was tolerated well and common toxic effects were myelosuppression, nausea, vomiting and alopecia. One patient died of septicemia as a result of agranulocytosis. These promising results seem to indicate the high degree of effectiveness of this combination chemotherapy against transitional cell carcinoma of the bladder.
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PMID:The management of advanced bladder carcinoma. 719 23


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