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)

28 patients with recurrent advanced breast cancer were treated with a salvage regimen consisting of vincristine, epirubicin and ifosfamide/mesna (VIE). All patients had poor prognostic characteristics defined as relapse within 12 months of chemotherapy or as relapse within a radiotherapy field. Chemotherapy was infused continuously through a central venous catheter using a portable pump. Ifosfamide (3 g/m2) mixed with mesna (3 g/m2) was infused for 7 days followed by epirubicin (50 mg/m2) mixed with vincristine (1.5 mg/m2) over a further seven days and alternated for a total of 6 weeks. 9 of the 28 patients (32%) responded to VIE (six partial and three complete responses). This included 6 of the 18 patients (33%) who had previously received doxorubicin or mitoxantrone, 6 of the 17 patients (35%) who had an inoperable in-field relapse after radiotherapy for locally advanced cancer, and 5 of the 21 patients (24%) relapsing within 6 months of previous chemotherapy. Median duration of response and overall survival were 3.7 and 6.9 months, respectively. Myelotoxicity was mild. One patient had neutropenic sepsis, 3 patients ahd grade 3 nausea and vomiting and one patient developed paralytic ileus attributed to vincristine. Central venous catheter complications occurred in 12 of 33 catheters requiring removal in 6. Continuous infusional chemotherapy using vincristine, epirubicin and ifosfamide achieves a 32% overall response rate in treatment-resistant advanced breast cancer, and is associated with minimal toxicity and a short treatment period. VIE may be a suitable alternative to conventional chemotherapy.
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PMID:Continuous infusion of vincristine, ifosfamide and epirubicin over 6 weeks in treatment-resistant advanced breast cancer. 854 Oct 98

Azathioprine is used in a variety of dermatological conditions. However, because of its side-effect profile, azathioprine is limited for use in patients with severe disease. An unpredictable, rare and potentially fatal side-effect of azathioprine is the development of a hypersensitivity reaction, often consisting of fever, hypotension and oliguria. We describe a 17-year-old patient with leucocytoclastic vasculitis who was placed on azathioprine; within 15 days of start of therapy, she developed a fever. Azathioprine was discontinued and an evaluation for sepsis was undertaken; all cultures were negative and the fever abated. Azathioprine was restarted 5 days later. After a single dose, fever, nausea and vomiting, diarrhoea, hypotension, tachycardia and oliguria developed and the patient was admitted to an intensive care unit. Azathioprine was discontinued and investigations revealed no sign of an infection. All the above signs and symptoms abated within 24 h and the patient was discharged from hospital in 7 days. A review of 28 case reports in the literature of azathioprine-induced hypersensitivity reactions suggest that most commonly a fever and gastrointestinal symptoms occurred on initial presentation. In addition, a maculopapular rash, urticaria, vasculitis, erythema multiforme or erythema nodosum may occur. Hepatotoxicity and nephritis have also been reported. The aetiology of the reaction is unknown but sudden onset of fever and hypotension suggests that this reaction may be due to cytokine or mediator release induced by azathioprine. As azathioprine is metabolized to 6-MP, rechallenges to both should be avoided in patients who experienced an azathioprine hypersensitivity-like reaction.
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PMID:Azathioprine hypersensitivity-like reactions--a case report and a review of the literature. 854

Eighteen patients with metastatic non-small cell lung cancer were treated with a combination of intravenous vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Medicament, Paris, France) 25 mg/m2 on days 1 and 8 and intravenous paclitaxel 175 mg/m2 on day 2 every 3 weeks. All patients were given granulocyte colony-stimulating factor 5 micrograms/kg/d subcutaneously on days 3 through 7 and 9 through 17 or until the absolute neutrophil count reached 10 x 10(9)/L or higher. One patient was enrolled in this study too recently to be assessed. The mean age of the remaining 17 patients was 59 years (age range, 33 to 75 years); all but one patient had refractory disease, mostly to cisplatin-containing regimens. Four patients were ineligible (two because of poor performance status and two because of previous exposure to vinblastine). Three partial responses were observed, with durations of 46, 64, and 140+ days. Four patients had stable disease and four had progressive disease. The most common side effect was neutropenia (five grade 4 and one grade 3); two patients died of leukopenic sepsis in the first cycle. Peripheral neuropathy was also common (four grade 1 and one grade 2 sensory neuropathy). Other toxic effects were anemia and nausea and vomiting. The median survival was 153 days in all patients and 179 days in eligible patients. The preliminary results in this ongoing study of combination vinorelbine and paclitaxel as second-line therapy for metastatic non-small cell lung cancer are promising, and using this regimen as first-line therapy is warranted.
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PMID:Pilot study of vinorelbine (navelbine) and paclitaxel in patients with refractory non-small cell lung cancer. 861 Feb 31

Amifostine (WR-2721) was originally developed as a radioprotective agent. In animals, it protects normal tissues from the damaging effects of irradiation and, as shown in more recent studies, of several cytotoxic agents. Protection of tumours is generally reduced compared with that of normal tissues in animals, suggesting that amifostine may increase the therapeutic window of cytotoxic therapies. Clinical data concerning amifostine suggest that cytotoxic chemotherapy-induced haematological toxicity and cisplatin-induced neurotoxicity, nephrotoxicity and ototoxicity are decreased upon administration of amifostine prior to cytotoxic drugs. Similarly, amifostine reduces damage to normal tissues caused by radiotherapy. Available data show that this protection is achieved without adversely affecting tumour response or patient survival. In 1 large trial, the reduction in cyclophosphamide- and cisplatin-related toxicities manifested as a decrease in the incidence and severity of neutropenia-related fever and sepsis and in the number of patients with ovarian cancer who discontinue therapy before completion of treatment, thus improving the tolerability of this antineoplastic regimen. In addition, the incidences of cisplatin-induced nephro- and neurotoxicity were reduced. Increased doses of cytotoxic therapy have also been administered when amifostine was given prior to therapy, which may increase tumour response. The predominant adverse effect associated with amifostine are hypotension, nausea and vomiting, somnolence and sneezing. Thus, amifostine is likely to be a useful adjuvant to the treatment of patients with malignancy, particularly those receiving cyclophosphamide plus cisplatin. discontinued therapy before completion of treatment, thus improving the tolerability of this antineoplastic regimen. In addition, the incidences of cisplatin-induced.
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PMID:Amifostine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential as a radioprotector and cytotoxic chemoprotector. 861 69

Amonafide (nafidimide), a synthetic organic compound with an inhibitory effect on cellular replication, was used in a phase II study conducted by the Illinois Cancer Center in order to assess its efficacy and toxicity in advanced or recurrent squamous cell cancer of the head and neck. Eligible patients had received no more than one prior adjuvant or neoadjuvant chemotherapy, had normal bone marrow, renal and hepatic function, ECOG performance status of 0-2, and bidimensionally measurable disease. Eligible patients were administered amonafide at a starting dose of 300 mg/m2 for five consecutive days every 3 weeks with dose escalation or de-escalation according to established hematologic criteria in the absence of disease progression. Nineteen of 22 entered patients were evaluable for response and all patients were evaluable for toxicity. Eleven of 19 patients achieved stable disease. Median time to progression after start of treatment was 57 days, for the 18 patients for whom the date of progression is known. There were no partial or complete responses. Hematologic toxicity was dose limiting with grade 3-4 neutropenia in 50 percent of patients and 4 deaths associated with neutropenic sepsis. Non-hematologic toxicity was mild to moderate with nausea and vomiting predominating. In this study, amonafide was a myelotoxic, inactive treatment in advanced/recurrent head and neck cancer. Further use in head and neck cancer appears unwarranted.
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PMID:Phase II study of amonafide in the treatment of patients with advanced squamous cell carcinoma of the head and the neck. An Illinois Cancer Center study. 872 54

Sixty patients with rheumatoid arthritis who were administered weekly low dose methotrexate (MTX) were retrospectively analyzed for their untoward effects of MTX by interviewing to the patients and by the medical records. Cough and sputa were the most frequent symptoms (23.3%) and gastrointestinal symptoms were the next (20%). Five of 60 patients (8.2%) showed liver function test abnormalities, and four (6.7%) exhibited transient exacerbation of arthralgia for several hours to a few days after MTX administration. Three patients (5%) suffered from interstitial pneumonitis. Hair loss was seen in 3 patients (5%), and headache, leucocytepenia, fever, skin eruption, abnormal taste, hemorrhagic cystitis, and flashing were experienced in a patient, respectively. Three (5%) suffered from fungal infection, and herpes zoster, sepsis, and osteomyelitis were experienced in each one patient, respectively. MTX was withdrawn in three patients (5%) because of cough and sputa the drug was withdrawn in other three patients because of the interstitial pneumonia, and was drawn in another three patients because of transient exacerbation of arthralgia. The drug was withdrawn in each one patient, because of nausea and vomiting, skin eruption, osteomyelitis, and sepsis, respectively. Overall, MTX were withdrawn in 21 patients (35%), and, of those, 13 patients (21.7%) because of untoward effects and 8 patients (13.3%) because of the lack of efficacy.
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PMID:[Untoward effects of low dose methotrexate therapy in rheumatoid arthritis]. 877 88

The experience with the first 100 hemodialysis sessions at the Owena Dialysis Centre of the University College Hospital, Ibadan (UCH) is hereby presented. A total of 9 patients were dialysed during a 7-month period. The femoral vein was the most often utilised vascular access route (53 episodes in 5 patients) while a forearm fistula was functional in only one patient. The dialyzer and blood lines were reused for each patient for a maximum of 5 times. Technical problems encountered were: power failure (12 episodes), ruptured dialyzer (3), water-pipe leakage (4) machine breakdown (2) and heparin pump failure (2). Clinical problems were: failure of fistula access (2), thrombosed femoral veins (2), clotted cannula (3), low arterial pressure (20); nausea and vomiting (2), pruritus (46), muscle cramps (5), Sepsis (8) and hypotension (2). Six patients discontinued treatment after less than 10 dialyses due to financial constraints. The high cost of hemodialysis remains the major setback to its use in the treatment of end-stage renal disease in developing countries; there is the need for acceptable improvisation to reduce the overhead cost so as to make it available to most patients requiring dialysis.
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PMID:Hemodialysis in Ibadan: a preliminary report on the first 100 dialysis. 879 61

Thirty-six patients with advanced epithelial ovarian cancer received epirubicin as second-line therapy after primary treatment with carboplatin and cyclophosphamide. Thirty-four patients were evaluatable for response, 36 for toxicity. There were 9 responses (response rate 26.4%, 95% CI = 12.9-44.4), 2 complete and 7 partial. Median duration of response was 149 days (range 42-183); 4 patients with partial remission are still on study. Toxicity consisted of fatal cardiac failure and paravenous injection (1 patient), fatal leukopenia and sepsis (1 patient), and severe loss of appetite, nausea and vomiting, fatigue, and general malaise in 3 patients. Platelet nadir grade 4 (WHO) was observed in 2 patients while leukocyte nadir grade 4 was seen in 3 patients. The present study showed a high response rate from standard-dose epirubicin. Toxicity was acceptable in most patients, but 2 patients died from treatment complications which gives a treatment-related mortality rate of 6%. Response was primarily seen in patients with minor tumor load and in good general condition.
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PMID:A phase 2 study with epirubicin as second-line treatment of patients with advanced epithelial ovarian cancer. 891 Jun 29

This randomized, multinational, multicenter study was designed to determine the response rate of gemcitabine monotherapy and cisplatin/etoposide combination therapy in chemotherapy-naive patients with advanced, recurrent, and/or metastatic non-small cell lung cancer (stage IIIA [if inoperable], IIIB, or IV). One group of patients received gemcitabine 1,000 mg/m2 intravenously once a week for 3 weeks (days 1, 8, and 15) followed by a 1-week rest period. The second group received cisplatin 100 mg/m2 intravenously on day 1 of each 28-day cycle in combination with etoposide 100 mg/m2, administered on days 1, 2, and 3 following the cisplatin infusion. Each patient was allowed to remain on study up to a maximum of six cycles. The planned interim analysis was based on the 117 patients in the study, 116 of whom were randomized up until November 20, 1995. The efficacy analysis was performed on the 107 patients who had data from a minimum of two cycles, whereas the safety analysis was based on data from all 116 randomized patients. In the gemcitabine arm there were 10 of 52 (19%) partial responders; in the cisplatin/etoposide arm there were four (7%) of 54 partial responders. There was a statistically significant difference in the response rates between the two arms, with a 95% confidence interval of 0.6% to 32.1% (P = .040). The median time to progressive disease was 4.2 months for gemcitabine patients and 3.7 months for cisplatin/etoposide patients. There was significantly more alopecia and nausea and vomiting in the cisplatin/etoposide arm compared with the gemcitabine arm, as well as two cases of neutropenic sepsis in the cisplatin/etoposide arm. These data indicate that single-agent gemcitabine is at least as effective as the combination of cisplatin/etoposide in the treatment of advanced non-small cell lung cancer and has an improved safety profile.
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PMID:A randomized study of gemcitabine monotherapy versus etoposide/cisplatin in the treatment of locally advanced or metastatic non-small cell lung cancer. 920 10

9-Nitrocamptothecin (9NC) is a water-insoluble topoisomerase I inhibitor with a broad antitumor activity in animal models. To determine the maximum tolerated oral dose (MTD), a phase I study was performed in patients with advanced cancer refractory to conventional chemotherapy. 9NC was administered orally with escalating doses to cohorts of five patients beginning at 1 mg/m2/day for five consecutive days every week for 4 weeks. Increments were 0.5 mg/m2/day for each cohort. Toxicity was evaluated in 28 patients diagnosed with various malignancies. Seven patients received 1 mg/m2/day for 28 weeks; 10 patients, 1.5 mg/m2/day for 68 weeks; and 26 patients, 2 mg/m2/day for 159 weeks. At 1.5 mg/m2/day or higher, the dose-limiting toxicity was hematologic, with grade 4 anemia in eight (29%); neutropenia in seven (25%) and thrombocytopenia in five (18%). Grade 2 or higher toxic effects occurred at each dose level: nausea and vomiting in 15 (54%), diarrhea in nine (32%), chemical cystitis in seven (25%), neutropenic sepsis in six (21%) and weight loss in five (18%) (N=28). Responses were observed after 2-8 weeks of therapy in five patients with pancreatic, breast, ovarian and hematologic tumors. Fourteen patients had a disease stabilization and one patient received treatment up to 18 months. The MTD of 9NC given orally has been estimated at 1.5 mg/m2/day for five consecutive days weekly. 9NC may be tolerated for sustained periods of time, but has the potential for significant hematologic, gastrointestinal and urinary bladder toxicity. Significant antitumor activity was observed, warranting further clinical investigations.
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PMID:A phase I clinical and pharmacological study of oral 9-nitrocamptothecin, a novel water-insoluble topoisomerase I inhibitor. 949 90


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