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)

For phase II studies in patients with solid tumors, the National Cancer Institute recommended that the starting dose of fludarabine phosphate be 20 mg/m2/day as a short intravenous infusion for 5 days every 21 days. Twenty-one patients with untreated, advanced, measurable colorectal carcinoma received fludarabine phosphate as a 30-minute infusion at a median dose of 25 mg/m2/day (range 15-35 mg/m2/day) for 5 consecutive days repeated every three weeks. Antitumor response was evaluated following two courses of therapy. No patient achieved complete or partial response. Minor regression of lung metastases occurred for less than 12 weeks in one patient. Therapy was generally well tolerated. Frequent toxicities included lymphopenia, mild nausea and vomiting, mucositis, and anorexia. One patient died of sepsis, bleeding, and progressive disease while she was severely myelosuppressed. Neurotoxicity was not observed in any patient. Fludarabine phosphate at this schedule and dose range is inactive against colorectal carcinoma.
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PMID:Phase II study of fludarabine phosphate in patients with advanced colorectal carcinoma. 245 66

To augment the antitumor effect of high-dose melphalan and determine pharmacokinetics we conducted a phase I trial of escalating doses of high-dose IV melphalan with the chemosensitizer misonidazole for patients with advanced colorectal carcinoma. Fourteen patients with modified Dukes D adenocarcinoma of the colorectum were treated with a single course of melphalan (40-60 mg/m2 i.v. bolus q.d. X 3 days) and misonidazole (1-3 g/m2 p.o. q.d. X 3 days) followed by autologous bone marrow transplantation. Toxicity consisted of severe myelosuppression, moderate nausea and vomiting, and mild mucositis and diarrhea. One patient developed unexplained renal tubular acidosis, and a diffuse encephalopathy occurred in another patient. Three patients died within the first 30 days after the start of treatment, two due to tumor progression and one due to sepsis and disseminated intravascular coagulation-induced intracerebral hemorrhage. Six of 14 patients achieved a partial response, and the median response duration was 4 months (range 3-10 months). Analysis of misonidazole serum concentrations showed similar pharmacokinetics to those previously reported, suggesting no significant drug interaction with intravenous melphalan. Mean peak serum concentrations ranged from 81.8 micrograms/ml to 115.2 micrograms/ml at the second and third misonidazole dose levels, which approximate those known to provide effective chemosensitization with melphalan in animal models. In this phase I study, we showed that maximally tolerated doses of intravenous melphalan can safely be combined with oral misonidazole. In view of the large volumes of oral misonidazole required at the highest dose level, subsequent studies to determine the maximally tolerated dose of misonidazole should employ the intravenous form.
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PMID:High-dose melphalan, misonidazole, and autologous bone marrow transplantation for the treatment of metastatic colorectal carcinoma. A phase I study. 265 May 27

Forty-nine evaluable patients with advanced or recurrent endometrial carcinoma who were no longer controllable with surgery, radiotherapy, and hormonal therapy and who had not received prior chemotherapy were treated with cisplatin 50 mg/m2 intravenously every 3 weeks. Two complete responses (4%) and eight partial responses (16%) were observed among the 49 patients. Twenty-two (45%) exhibited stable disease for at least 2 months, while 17 patients (35%) progressed less than 2 months after initiating chemotherapy. Adverse effects included mild leukopenia (31%), nausea and vomiting (72%), and mild azotemia (51%). Only 2 patients experienced life-threatening toxicity; one related to renal failure and the other to sepsis and shock. Cisplatin thus has definite activity when given at the dose and schedule tested to patients with endometrial carcinoma who have not received prior chemotherapy.
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PMID:Phase II trial of cisplatin as first-line chemotherapy in patients with advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group Study. 270 69

Aztreonam was administered to 25 neonates (16 term, 9 premature) with clinically and bacteriologically proved gram-negative infections. Ten patients had meningitis, 9 had septicemia and 6 had urinary tract infections. Patients were between 1 and 28 days of age. Aztreonam was administered intravenously in doses ranging from 40 to 120 mg/kg/day for 10-30 days, depending on the causative organism. All CSF, blood and urine cultures were sterile 48 h after drug treatment had begun. There was no incidence of bacteriologic relapse. Body temperature returned to normal in 96% of patients within 3-4 days of therapy. Aztreonam was well tolerated. One infant experience nausea and vomiting, but no patient was withdrawn from therapy due to adverse reactions.
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PMID:Successful response of severe neonatal gram-negative infection to treatment with aztreonam. 273 46

Twenty patients with focal malignant obstruction of the major bile ducts (6 cholangiocarcinoma, 8 colorectal, 3 hepatoma, 2 unknown primary, and 1 gastric cancer) were treated on a protocol examining the toxicity and efficacy in relieving jaundice of external beam radiation therapy (4500 cGy in 300 cGy fractions) combined with continuous hepatic arterial (15 patients) or peripheral venous (5 patients) fluorouracil infusion. Toxicity of this regimen consisted of anorexia with mild nausea and vomiting in 55% of patients and gastric ulceration (responsive to medical management) in 15% of patients. One patient exhibited transient grade 2 hepatic toxicity and one had asymptomatic grade 4 leukopenia. Of 14 patients treated without prior biliary drainage, 8 exhibited a decrease in bilirubin levels from a mean of 14.5 mg/dl to 1.5 mg/dl. Four of six patients with biliary drainage catheters at the start of treatment were able to have them removed without reobstruction. For the 8 responding patients among those who did not have cholangiocarcinomas, the median response duration was 5 months with a median survival from treatment of 6.5 months. For the 4 responding patients with cholangiocarcinoma, the median response duration was 16 months with a median survival from treatment of 20 months. All responders did not have a return of jaundice due to reobstruction of the major ducts (until death or to the present). All responders who have died did so due to tumor progression outside of the treated field except for one who died of unrelated causes. The mean number of proven or presumed episodes of cholangitis per patient was virtually identical in those without (1.8) and those with stents/tubes (1.4, p = 0.561). This regionally focused combined modality cytotoxic therapy was able to relieve obstruction in the majority of patients without excess morbidity (including a lack of any detectable increase in sepsis). Thus, it appears feasible to consider randomized studies of this cytotoxic approach versus standard mechanical drainage procedures to define the relative risks and benefits of each.
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PMID:Combination chemo-radiation therapy for jaundice due to focal malignant obstruction of the major bile ducts. 277 30

We treated nine patients diagnosed as inoperable, but localized non-small cell lung cancer with aggressive high-dose radiation therapy and two cycles of concomitant cisplatin and 5-fluorouracil (5-FU) to determine the feasibility of this approach for this disease. This combined modality program was well tolerated by seven of our nine patients. One who had a poor initial performance status died of sepsis. Another could not tolerate the nausea and vomiting. Only one patient has suffered a local failure inside the irradiated areas. Eight have died, and 5 of 9 survived at least 1 year. The survival is at least consistent with that associated with radiation therapy alone.
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PMID:Concurrent chemotherapy and radiation therapy for limited unresectable non-small cell carcinoma of the lung. A phase I study. 283 50

Six Caribbean patients with histologically and immunologically characterized adult T-cell leukemia/lymphoma (ATL) were treated intravenously (IV) with 2'-deoxycoformycin (DCF) at a dose of 5 mg/m2 on days 1, 2, 8, 15, and 22 with four additional weekly doses to convert any partial responses (PR) to complete responses (CR). Patients were considered eligible for this study if refractory to or relapsed from combination chemotherapy, had a life expectancy of 4 weeks or more, a performance status greater than or equal to 50%, normal renal and hepatic function, and no chemotherapy within 4 weeks. Clinical characteristics of the patients in this study included lymphadenopathy in five patients, skin involvement in four patients, bone marrow infiltration in five patients, and central nervous system involvement in two patients. Circulating ATL cells were present in four patients, and three were hypercalcemic. Of five patients evaluable for response, there was one PR of 1 month, and two minor responses lasting 2 and 3 weeks. The median duration of survival for all treated patients was 3 weeks or more. The DCF was associated with moderate side effects, including conjunctivitis in three patients, nausea and vomiting in two patients, progressive hepatic insufficiency in one patient, and moderate myelotoxicity in three patients. Infections occurred in four patients, including two cases of oral candidiasis and two cases of fatal neutropenic sepsis in patients receiving concurrent intrathecal methotrexate. As a single agent, DCF appears to have limited activity in advanced refractory/relapsed ATL. Studies in the future should explore DCF in combination with other cytotoxic agents as initial therapy in better-risk patients.
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PMID:2'-Deoxycoformycin therapy in adult T-cell leukemia/lymphoma. 289 Apr 28

Twenty patients with stage III and IV diffuse well-differentiated lymphocytic lymphoma were treated with combination chemotherapy consisting of BCNU, cyclophosphamide, vincristine, melphalan and prednisone (M-2). Treatment was given every 5 weeks for 11 cycles in responding patients. The median age of the patients was 62 years (range 45-76). There were 12 complete remissions and 6 partial remissions for an overall response rate of 90%. The median duration of remission was 24 months (range 12-79 months) and was identical for complete responders and partial responders. All but 2 responding patients have been subsequently retreated for relapse. The median survival was 84 months (range 1-108 months). Myelosuppression was mild. Nausea/vomiting, neuropathy, alopecia and gastrointestinal symptoms from prednisone were seen in the minority of patients. One patient expired from sepsis/neutropenia during the first cycle of therapy. The M-2 protocol produces effective remissions in diffuse well-differentiated lymphocytic lymphoma. The relapse and survival pattern are similar to the results achieved with other chemotherapy regimens in low-grade lymphoma.
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PMID:Diffuse well-differentiated lymphocytic lymphoma: chemotherapy with BCNU, cyclophosphamide, vincristine, melphalan and prednisone. 305 72

The regimen of doxorubicin (DOX), ifosfamide (IFF), and dacarbazine (DTIC) (AID) for previously untreated inoperable or metastatic sarcoma has acceptable toxicity with significant activity. Twenty patients received 79 courses of DOX (60-75 mg/m2) with or without DTIC (900 mg/m2) by continuous infusion over 72 hours with escalating doses of IFF and mesna uroprotection. Nineteen patients were evaluable for toxicity. Myelosuppression was dose-limiting. The maximum tolerated dose was DOX at 60 mg/m2, DTIC at 900 mg/m2, and IFF at 7500 mg/m2 per course. Of the 79 courses analyzed, 33 (42%) resulted in wbc counts less than 1000/microliter; 14 (18%) were complicated by fever and neutropenia, and three by sepsis. There were no toxic deaths. Relative platelet sparing was observed and nadirs were brief. In contrast to bolus-dose DTIC divided over 5 days, DTIC by continuous infusion did not add significantly to gastrointestinal toxicity. Nausea and vomiting was well controlled by antiemetics. Mucositis occurred sporadically. Unlike our phase II study of IFF alone, no CNS or renal toxicity was observed. No cardiac toxicity was encountered, although only four patients have received greater than 450 mg/m2 of cumulative DOX. One episode of DOX extravasation occurred despite a long iv line that extended to the axilla. No serious tissue damage was observed, perhaps due to the dilute solutions of DOX used. Partial responses were seen in eight of 18 evaluable patients (44%) and in six of 11 patients at or near the phase II level. Two additional patients with minimal response have continued tumor regression. The median number of courses before partial response was four (range, one to five). The median duration of response has not been reached (3+ to 10+ months). An inoperable primary has been rendered surgically resectable in one patient. Activity in previously untreated sarcomas should be further evaluated in a randomized phase III study against a standard DOX-containing combination.
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PMID:Doxorubicin, ifosfamide, and dacarbazine (AID) with mesna uroprotection for advanced untreated sarcoma: a phase I study. 308 17

One hundred twenty-four children and young adults with recurrent tumors, predominantly sarcomas, were treated with the combination of ifosfamide, etoposide, and the uroprotector, mesna (2-mercaptoethane sulphonate), in a phase II trial. The treatment regimen consisted of 12 cycles of therapy administered every 3 weeks. After evaluation of the tumor response to chemotherapy alone, radiation or surgery was used to eradicate residual sites of metastatic disease where possible. At the present time, 77 patients are evaluable for response to the chemotherapy; 43 of the patients have experienced a significant reduction in the tumor size in response to the chemotherapy alone (39 partial responses [PR] and four complete responses [CR]). Sixteen of 17 patients with Ewing's sarcoma, nine of 13 with rhabdomyosarcoma, four of eight with peripheral neuroepithelioma, three of eight with osteosarcoma, and 11 of 31 with other tumors have responded with a PR or CR. The toxicity of the regimen was acceptable. Moderate or severe toxicity evaluated on a per cycle basis included: neutropenia, 97%; thrombocytopenia, 32%; nephrotoxicity, less than 1%; mucositis, 1%; neurologic toxicity, 2%; nausea and vomiting, 13%; hemorrhagic cystitis, less than 1%. Fever was present after 33% of cycles and sepsis following 7%. One patient died due to sepsis and pancytopenia. At the present time, only seven of the 43 patients who responded to the chemotherapy regimen have relapsed, with a median follow-up of 10 weeks after the response. This drug combination is highly active in the treatment of recurrent sarcomas and other tumors in children and young adults.
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PMID:Ifosfamide with mesna uroprotection and etoposide: an effective regimen in the treatment of recurrent sarcomas and other tumors of children and young adults. 311 35


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