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)

Seventy-nine patients with metastatic breast cancer underwent examination of their bone marrow as part of their staging workup. Thirty-one (39%) showed no evidence of bone marrow involvement (BM-); 48 (61%) were found to have bone marrow metastases (BM+). Both groups of patients were treated with intensive chemotherapy with 5-FU, Adriamycin, cyclophosphamide, methotrexate, and nonspecific immunotherapy with BCG, methanol extraction residue, or Levamisole. The groups were comparable in age, race, menopausal status, and disease-free interval; however, the BM+ group had a higher proportion of patients with dominant osseous disease and a somewhat lower overall tumor burden. Ten of 21 patients in the BM+ group treated with 100% of the calculated dose of chemotherapy are still alive, compared with only three of 27 patients treated with lower doses. A similar dose response was observed in the BM- group. Myelosuppression was more common and more severe in the BM+ group. Hematologic support, i.e., packed erythrocytes and platelet transfusions, was required in 60% of BM+ patients, as opposed to 26% of BM-. Infectious complications were also higher in the BM+ group, in which five episodes of sepsis and two infectious deaths were observed. These results suggest that metastatic breast cancer patients with bone marrow invasion achieve excellent palliation with aggressive high-dose chemotherapy. Higher morbidity requiring aggressive supportive care suggests that these patients should be treated by physicians and centers experienced in their management.
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PMID:Combination chemotherapy for breast cancer metastatic to bone marrow. 723 95

A phase II trial was performed to assess the efficacy and toxicity of the combination mitoxantrone (MXN) and vinorelbine (VNR) as first-line chemotherapy for metastatic breast cancer. Forty-one patients with metastatic disease or local relapse recruited between March 1991 and April 1993 received a first-line chemotherapy treatment consisting in 12 mg/m2 intravenous (IV) bolus of MXN on day 1 followed by a 20-minute perfusion of 25 mg/m2 of VNR on days 1 and 8. Cycles were repeated every 21 days until evidence of disease progression or of severe toxicity. Thirty-seven patients were evaluable for response and all 41 for toxicity. An objective response was observed in 19 patients (51%; 95% confidence interval, 45 to 74%). The response was complete in a further 11 (30%). Median time to treatment failure was 9 months. Median survival was 14 months. There were no treatment-related deaths. Limiting toxicity was myelosuppression. Leukopenia occurred in 29 patients (71%) and was grade 3 or 4 in nine of these (15%). Grade 2 or 3 anemia was encountered in six patients (15%), grade 1 thrombocytopenia in one, neurotoxicity (constipation) in two, and grade 2 or 3 alopecia in 12 (29%). Nausea/vomiting requiring antiemetic treatment was experienced by only two patients (5%). There were two cases of septicemia treated by antibiotic therapy in hospital.
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PMID:[Combination of mitoxantrone-vinorelbine as first-line chemotherapy for metastatic breast carcinoma]. 765 48

Iododoxorubicin 80 mg m-2 i.v. was given 3 weekly for a maximum of six cycles as first-line chemotherapy to 14 evaluable women with metastatic breast cancer. The response rate was 14% (95% confidence intervals 4-40%); median time to progression was 3.5 months (range 0.7 to > 9.3) and median survival was 10.2 months (range 2.3 to > 20.4). Neutropenia was the main toxicity but was not associated with severe sepsis. Two patients had a significant (> 10%) but asymptomatic fall in cardiac ejection fraction; other toxicities were mild. Plasma pharmacokinetics was studied during the first cycle of treatment. Iododoxorubicin was extensively metabolised to iododoxorubicinol. Neutropenia and thrombocytopenia were both significantly correlated with the area under the concentration-time curve (AUC) for iododoxorubicin and the total AUC for iododoxorubicin and iododoxorubicinol. Quality of life (QOL), evaluated by self-report questionnaire and interview, showed little evidence of benefit in terms of physical symptom relief, level of activity, psychological symptoms or global evaluation of QOL during treatment. Iododoxorubicin is subjectively less toxic than standard anthracyclines, but at the dose and schedule used has limited activity in metastatic breast cancer, possibly because iododoxorubicinol is not clinically active.
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PMID:Iododoxorubicin in advanced breast cancer: a phase II evaluation of clinical activity, pharmacology and quality of life. 814 61

Ifosfamide, carboplatin, cisplatin, etoposide, and paclitaxel are chemotherapeutic agents active in treating many malignant diseases. The ICE combination (ifosfamide/carboplatin [or cisplatin]/etoposide) has been studied in breast cancer, small cell and non-small cell lung cancer, testicular cancer, lymphoma, and other malignancies with promising results. We conducted a dose-escalation study of paclitaxel in combination with ICE (ICE-T) to evaluate the toxicity and define the maximum tolerated dose of paclitaxel. To date, 24 patients have been treated with ICE-T. Patients had to have no or minimal prior chemotherapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate bone marrow, liver, and kidney function. The doses of ICE were as follows: ifosfamide 1.25 g/m2/d days 1 to 3, carboplatin 300 mg/m2 day 1, and etoposide 80 mg/m2/d days 1 to 3. Paclitaxel was given at a dose of 120 mg/m2 to five patients, 135 mg/m2 to five patients, 150 mg/m2 to three patients, and 175 mg/m2 to 11 patients. All patients received granulocyte colony-stimulating factor support. The most common side effect was neutropenia. Grade 4 neutropenia and thrombocytopenia occurred during 34% and 20% of 94 cycles, respectively, with leukopenic fever occurring during 14% of cycles. No treatment-related death or sepsis occurred due to brief nadir durations of 3.5 days for neutropenia and thrombocytopenia. Other toxicities were mostly mild to moderate and did not require dose modification, although alopecia was universal. Nine patients (100%) with metastatic breast cancer and four (67%) with soft tissue sarcoma have attained documented objective responses with four complete remissions (one breast cancer and three sarcoma patients). The maximum tolerated dose of paclitaxel has not yet been defined, and the study is ongoing. In conclusion, this pilot study showed that ICE-T is safe and tolerable. The response to ICE-T is encouraging and warrants further study with this regimen.
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PMID:Ifosfamide, carboplatin, etoposide, and paclitaxel chemotherapy: a dose-escalation study. 867 54

Peripheral blood progenitor cell (PBPC) autografts have a number of advantages over autologous bone marrow transplantation (ABMT) as haematopoietic support after high-dose chemotherapy in patients with breast cancer. These may include less contamination by tumour cells, reduced morbidity and mortality and additional dose escalation of chemotherapy. A dose-escalation study is described using recombinant granulocyte colony-stimulating factor (G-CSF; filgrastim) primed PBPC support and post-infusion filgrastim for patients with high-risk or metastatic breast cancer. The regimen involved the use of cyclophosphamide, thiotepa and carboplatin at five dose levels. The main problem to emerge was organ toxicity induced by chemotherapy or sepsis. Patients receiving higher levels of chemotherapy were therefore allocated or not to an additional regimen involving pentoxifylline, ciprofloxacin and dexamethasone in an attempt to inhibit tumour necrosis factor alpha (TNF-alpha) which is believed to be one of the principal mediators of chemotherapy-related organ toxicity. The incidence of bilirubin elevations, weight gain > 5% and veno-occlusive disease (VOD) was lower in patients receiving the 'anti-TNF' therapy. The simultaneous use of PBPC support and 'anti-TNF' therapy therefore allows a substantial increase in chemotherapy dosage. Further studies with larger patient numbers are required to show whether this decreased toxicity also produces increased patient survival.
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PMID:High-dose chemotherapy for breast cancer: clinical advantages of autologous peripheral blood progenitor cells (PBPC) compared with autologous bone marrow transplantation (ABMT). 875 Jan 43

This phase I dose-finding study examined the effects of the combination of doxorubicin and docetaxel (Taxotere) in 42 women with metastatic breast cancer. The combination was studied at six different dosing levels. The maximum tolerated doses were defined as doxorubicin, 50 mg/m2, and docetaxel, 85 mg/m2, with sepsis as the dose-limiting toxicity. Activity was observed at all dose levels, especially at the highest dose levels (50/60, 50/75, 50/85, and 60/60 mg/m2), with a response rate of 81% (95%; confidence interval, 62.5% to 92.5%) in patients treated at these dose levels. The response rate in patients with visceral disease was 74%, and 82% in patients with liver metastasis. Adjuvant chemotherapy with or without anthracyclines did not affect the response rate. The recommended doses were doxorubicin, 50 mg/m2, and docetaxel, 75 mg/m2, or 60 mg/m2 of both drugs, administered on day 1 every 3 weeks, without granulocyte-colony stimulating factor (G-CSF, filgrastim [Neupogen]) support. Neutropenia was the only grade 3 or 4 adverse event. There were no cases of congestive heart failure, a significant decrease in left-ventricular ejection fraction, or interruption of treatment because of fluid retention.
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PMID:Docetaxel in combination with doxorubicin: a phase I dose-finding study. 921 22

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is a highly active single agent in the treatment of breast cancer. However, its optimal incorporation into combination regimens awaits definition. We added paclitaxel, administered by 1-hour infusion, to a previously described combination regimen that included mitoxantrone, 5-fluorouracil, and high-dose leucovorin. Forty-six patients with metastatic breast cancer received the following regimen as first- or second-line treatment: paclitaxel 135 mg/m2 by 1-hour intravenous infusion on day 1; mitoxantrone 10 mg/m2 by intravenous bolus on day 1; 5-fluorouracil 350 mg/m2 by intravenous bolus on days 1, 2, and 3; and leucovorin 300 mg intravenous over 30 to 60 minutes, immediately preceding 5-fluorouracil on days 1, 2, and 3. Courses were administered at 3-week intervals for a total of eight courses in responding patients. Of 45 assessable patients, 23 (51%) had major responses. Previous chemotherapy, and in particular previous treatment with doxorubicin, did not affect response rate. The median response duration was 7.5 months. Myelosuppression was moderately severe, with 76% of courses resulting in grade 3 or 4 leukopenia. There were four treatment-related deaths, two sepsis, one congestive heart failure, and one sepsis and congestive heart failure, the last two after a large cumulative anthracycline dose. This combination regimen was active as first- or second-line therapy for metastatic breast cancer, although how its activity compares with that of other combination regimens or with paclitaxel alone is unclear. Myelosuppression was more severe than had been anticipated based on previous results with the mitoxantrone/5-fluorouracil/high-dose leucovorin regimen or with single-agent paclitaxel administered at this dose and schedule. The infrequent development of cardiotoxicity in these patients suggests that the paclitaxel/mitoxantrone combination may not share the problems previously reported with paclitaxel/doxorubicin combinations. We have embarked on a phase I/II trial of paclitaxel/mitoxantrone and have determined the maximum tolerated dose to be 200 mg/m2 and 10 mg/m2, respectively, without the use of cytokines. Fifteen patients have been treated at the maximum tolerated dose, and it is too early to assess results.
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PMID:Paclitaxel with mitoxantrone with or without 5-fluorouracil and high-dose leucovorin in the treatment of metastatic breast cancer. 937 96

We report long-term results of high-dose cyclophosphamide, etoposide and carboplatin with ABMT in 20 patients with metastatic breast cancer. Median age of the group was 41 years, ECOG performance status = 0 in 18 patients and 1 in two patients. Twelve patients had received adjuvant chemotherapy. Predominant sites of metastases were lung (eight), chest wall (four), liver (four), bone (three) and lymph nodes (three). Response to pretransplant chemotherapy was complete (CR) in four patients, partial (PR) in 10 patients and stable (SD) in five patients. After high-dose chemotherapy eight patients were in CR, six PR, four SD and one progressive disease. Two patients died of regimen-related toxicities (candidal sepsis and alveolar hemorrhage). With a median follow-up period of 55 months (minimum 48 months), 12 patients have died of recurrent breast cancer, one died of toxicity of salvage chemotherapy, two are alive with disease, two are alive and free of progressive disease. One patient with relapsed disease was lost to follow-up. Median event-free survival is 6 months and median overall survival is 17 months. All three of the long-term disease-free survivors had predominantly nodal disease. Two of these three patients presented with metastatic disease and received high-dose chemotherapy with ABMT as part of initial therapy for breast cancer; two of three attained CR to standard-dose cytoreductive therapy; none received doxorubicin-containing adjuvant chemotherapy.
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PMID:High-dose cyclophosphamide, etoposide and carboplatin with autologous bone marrow support for metastatic breast cancer: long-term results. 960

The purpose of this study was to determine the maximally tolerated dose of doxorubicin administered during two cycles of intensive chemotherapy with cyclophosphamide and doxorubicin without stem cell support in patients with advanced cancer and to assess the cumulative cardiac toxicity of the regimen by noninvasive radionuclide imaging and by pre-and postchemotherapy endomyocardial biopsies. Thirty-eight patients (thirty-six with high risk or metastatic breast cancer) were treated in a dose-escalation trial using a fixed dose of i.v. cyclophosphamide (4.2 g/m2) administered over 2 h on day 5 and escalating doses of doxorubicin (50-175 mg/m2) given as a 96-h continuous i.v. infusion on days 1-4, using Filgrastim (granulocyte colony-stimulating factor) for hematological support beginning on day 6. All patients underwent pretreatment, and 28 patients underwent postchemotherapy endomyocardial biopsies. Twenty-nine of 38 patients received two cycles of treatment (median number of days between cycles, 44; range, 34-62). Twenty-one patients had received doxorubicin previously at cumulative dose levels </=150 mg/m2; all patients had pretreatment endomyocardial biopsy scores less than 1. One patient treated at the highest dose level of doxorubicin (175 mg/m2) developed symptoms of mild congestive heart failure following two cycles of chemotherapy. Pre- and posttreatment radionuclide ejection fractions were 65 and 45%, respectively; this patient had a posttreatment endomyocardial biopsy score of 1 (damage to <5% of myocytes). One additional patient at this dose level had an asymptomatic biopsy score of 1, with a decrease in ejection fraction from 62 to 43%; this recovered to 58% 5 months after completion of chemotherapy. Six additional patients treated at lower dose levels had abnormal posttreatment endomyocardial biopsies without abnormal posttreatment ejection fractions. Nine patients received only one cycle of chemotherapy: five patients due to decreased cardiac ejection fraction following cycle 1 (two of these patients had normal endomyocardial biopsies, and two patients had biopsy scores of 1); one patient secondary to tumor progression following cycle one; one patient due to persistently detectable Clostridium difficile toxin in the stool; one patient refused cycle two; and one patient died following cycle one of complications related to sepsis. A single patient experienced a grand mal seizure associated with orthostatic hypotension, which was considered the dose-limiting toxicity. The median duration (over two cycles) of granulocytopenia (absolute granulocyte count <500/microliter) at the maximally tolerated dose level of 150 mg/m2 was 8.5 days (range, 5-13 days), and the median duration of thrombocytopenia (platelets <20,000/microliter) was 2.5 days (range, 0-9 days). The median duration of hospitalization including chemotherapy administration was 23 days (range, 19-36 days). Other toxicities included stomatitis, fever, diarrhea, and emesis. One patient developed acute leukemia 54 months posttreatment. We conclude that two courses of high-dose cyclophosphamide and doxorubicin using granulocyte colony-stimulating factor are feasible and safe with tolerable myocardial toxicity as evidenced by serial endomyocardial biopsies. The dose-limiting toxicity encountered was a grand mal seizure. The recommended Phase II dose is doxorubicin 150 mg/m2 administered as a 96-h infusion on days 1-4, with cyclophosphamide 4. 2 g/m2 on day 5 and G-CSF 5 microgram/kg/day started on day 6 and administered until the total WBC is above 10,000/microliter for three consecutive days.
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PMID:High-dose infusional doxorubicin and cyclophosphamide: a feasibility study of tandem high-dose chemotherapy cycles without stem cell support. 981 32

The purpose of this study was to evaluate the combination of cisplatin and vinorelbine (PVn) for relapsed and chemotherapy-pretreated metastatic breast cancer. Twenty-three patients with metastatic breast cancer and prior chemotherapy were entered in a phase II study between June 1993 and December 1994. Eleven patients were premenopausal and 12 were postmenopausal. Follow-up data up to June 1997 are presented. All patients received cisplatin at a dose of 90 mg/m2 divided over 3 days as 30 mg/m2 infused over 4 hours. Intravenous vinorelbine 25 mg/m2 was given on days 1 and 8 or 15 according to patients' blood counts. Cycles were given every 3 to 4 weeks. An overall response rate of 61% (16/23 patients) was observed. Complete remission was obtained in six patients (26%) and partial remission was obtained in nine patients (35%). The duration of response ranged from 3 to 9 months, with an average of 4 months. Stable disease was noted in 29.1% and progressive disease in 8.3%. Overall survival at 12 months was 50%, and at 36 months it was 8%. Five of 12 patients (42%) who had prior doxorubicin therapy responded well to cisplatin-vinorelbine. Of those 12, seven were refractory and progressive on a doxorubicin-containing regimen, one had complete remission, and four had partial remission. Hematologic toxicity was acceptable. Treatment was delayed because of neutropenia in nine cycles (9.2%) and grade 2 leukopenia occurred in 54% of cycles. Febrile neutropenia occurred in seven cycles (7.1%), and five cycles were complicated by documented sepsis (5.1%). No treatment-related mortality occurred. Thrombocytopenia (grade 3) was seen in 27% of cycles, with no patient having a platelet count below 50,000 or bleeding episodes. Other toxicities were not major or dose-limiting. In conclusion, the combination of cisplatin and vinorelbine produced good responses: 61% response rate (16 of 23 patients) in relapsed, refractory, and heavily pretreated metastatic breast cancer, with 50% survival at 1 year, 12% at 2 years, and 8% at 3 years. In addition, a response rate of 42% (5 of 12 patients) was seen in patients resistant to anthracyclines.
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PMID:Combination cisplatin-vinorelbine for relapsed and chemotherapy-pretreated metastatic breast cancer. 1036 41


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