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)

A prospective study was conducted to evaluate response rate and toxicity of the combination of cyclophosphamide, adriamycin, and cis-platinum in patients with disseminated hormonally resistant prostatic carcinoma. Twenty-two patients were entered in the study: 19 were evaluable for response. One patient achieved partial remission while 14 (73%) had stable disease. Four patients had progressive disease. Patients with stable disease and partial remission had subjective improvement and survived significantly (p less than 0.03) longer than patients with progressive disease (58 weeks vs. 22 weeks). Toxicity was mainly hematological, and one patient died from sepsis secondary to leukopenia. Nausea and vomiting was moderate to severe, with one patient refusing cis-platinum for that reason. Renal toxicity was tolerable and reversible. Lack of good measurable disease makes generalization difficult, but pointers from animal models, along with the biological activity suggested by our results, make this a worthwhile combination to be considered for a trial in a larger population with measurable disease or in a randomized trial vs. the more effective single agent.
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PMID:Evaluation of cyclophosphamide, adriamycin, and cis-platinum (CAP) in patients with disseminated prostatic carcinoma. A phase II study. 384 Mar 26

Nineteen patients with unresectable and metastatic adenocarcinoma of the pancreas and ampulla of Vater were treated with intermittent regional infusion of the celiac axis (CAI) with the combination of 5-fluorouracil, adriamycin, mitomycin-C, and streptozotocin (FAM-S). Three schedules with escalating doses were investigated. The arterial infusion was repeated at 4 weeks, and in responding and stable patients, I.V. FAM-S was continued at monthly intervals. Twelve patients had measurable disease, and in this group one complete response and seven partial responses occurred. Median duration of response was 6+ months and median survival for all patients was 5.2 months. Four patients had catheter-related complications (emboli, three, sepsis, one). Hematologic and gastrointestinal toxicity was minimal. Celiac artery infusion with FAM-S in locally extensive and metastatic adenocarcinoma of the pancreas and ampulla of Vater is a relatively simple procedure associated with low incidence of serious complications and toxicity but a higher response rate than previously reported. Induction of response with CAI and subsequent maintenance therapy with intravenous chemotherapy is under investigation.
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PMID:Intermittent regional infusion of chemotherapy for pancreatic adenocarcinoma. Phase I and II pilot study. 621 42

With the aim of increasing the dose intensity of chemotherapy in breast cancer, 14 patients with stage II-IV breast cancer were treated with FEC chemotherapy at 2 week intervals together with granulocyte colony-stimulating factor (G-CSF) 5 micrograms kg-1 s.c. on days 2-14. Five of six patients completed six courses of 5-fluorouracil 600 mg m-2, epirubicin 60 mg m-2 and cylcophosphamide 600 mg m-2 within 11 weeks. Eight patients were treated with 5-fluorouracil 700 mg m-2, epirubicin 70 mg m-2 and cyclophosphamide 700 mg m-2 and four had dose-limiting toxicity with sepsis, thrombocytopenia or mucositis. All patients who received G-CSF had satisfactory neutrophil counts by day 15 of each course. Cumulative anaemia and thrombocytopenia were observed, but treatment at the first dose was tolerable. Seven of eight patients with measurable disease had partial responses. This regimen permits a 50% increase in dose intensity compared with conventional treatment at 3 week intervals and warrants further evaluation.
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PMID:Phase I study of accelerated FEC with granulocyte colony-stimulating factor (Lenograstim) support. 754 38

We have evaluated the combination of ifosfamide, carboplatin, and etoposide (ICE) along with mesna in 46 patients with stage IV non-small cell lung cancer. Treatment consisted of ifosfamide (1.25 g/m2/d with mesna) and etoposide (80 mg/m2/d) given intravenously on days 1 to 3 and carboplatin (300 mg/m2) given intravenously on day 1 every 4 weeks. Eligibility criteria included measurable disease; adequate hematologic, hepatic, and renal functions; no prior chemotherapy; and an Eastern Cooperative Oncology Group performance status (PS) of 0 to 3. Two patients were lost to follow-up and one had received prior chemotherapy, leaving 43 patients evaluable for response and toxicities. There were 27 male and 16 female patients. Twenty-three patients had a PS of 0 or 1 and 20 had a PS of 2 or 3. Eighteen patients had received prior radiotherapy. There were two complete responses and nine partial responses. The response rate was 35% in PS 0 or 1 patients and 15% in PS 2 or 3 patients. The most frequent toxicity was myelosuppression; 44% of patients experienced grade 3 or 4 leukopenia and 14%, grade 3 or 4 thrombocytopenia. Patients receiving prior radiation were significantly more prone to develop leukopenia (P = .01). Five patients developed leukopenic fever, and three died of sepsis. Gastrointestinal toxicities were mostly mild. No neurologic or genitourinary toxicities were observed. The median length of survival was 209 days for patients with a PS of 0 or 1 and 123 days for the entire group. The 1-year survival rate was 22% and 19%, respectively, in these two patient subgroups. ICE is an active regimen in patients with metastatic non-small cell lung cancer and a good PS. Myelosuppression is the major dose-limiting toxicity. Hematopoietic growth factors may be indicated in subsequent studies, especially in patients who had prior radiation therapy. The therapeutic effect of ICE on patients with a poor PS remains unsatisfactory and requires further investigation.
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PMID:Ifosfamide/carboplatin/etoposide chemotherapy in patients with metastatic non-small cell lung cancer. 761 Mar 99

The Southwest Oncology Group conducted a trial of VM-26 (teniposide) in patients with advanced gastric cancer. VM-26 60 mg/m2 i.v. infusion over 30-45 minutes was given daily for 5 days every 21 days. Twenty-one eligible patients with measurable disease and a SWOG performance status of 0-2 were analyzed for response and toxicity. Partial responses were seen in 2 of the 21 eligible patients (9.5%). Median survival was 3.8 months. Severe of life-threatening toxicity was observed in 13/21 (62%) patients. This included two drug related deaths related to neutropenic sepsis and seven other patients with grade 4 granulocytopenia (< 500/mm3). Liver dysfunction and hypotension were seen less often and were not dose limiting. Although the modest activity seen was comparable to that of VP-16 (etoposide) as a single agent, the hematologic toxicity observed in this trial would likely preclude further trials of VM-26 (teniposide) in advanced gastric cancer.
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PMID:VM-26 in gastric cancer. A Southwest Oncology Group study. 815 75

We assessed the efficacy and toxicity of alternating non-cross-resistant chemotherapy in the treatment of advanced NSCLC. Cycles of cisplatin, methotrexate, doxorubicin, and cyclophosphamide were alternated monthly with cisplatin and etoposide. Patients had measurable disease, ECOG performance status 0-3, no previous chemotherapy, and stage II (inoperable), III, or IV disease without brain metastases. Between 1988 and 1990, 28 patients were entered in the study: 20 patients (71%) had stage IV disease, 19 (68%) were evaluable for response and toxicity; 4 (21%) responded. There were 3 partial responders (16%) and 1 complete responder (5%). The mean duration of response was 60.5 weeks (range: 32-105+ weeks), and the median time to progression was 12 weeks (range: 8-105+ weeks). The median survival time for all 28 patients was 24 weeks (range: 3-153+ weeks). The most significant toxicity was grade 3-4 leukopenia experienced by 63% of patients, but there were no episodes of sepsis and no treatment-related deaths. This regimen of alternating cycles of cisplatin-containing chemotherapy is safe, but its efficacy is not superior to other combination chemotherapy regimens.
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PMID:A phase II trial of alternating chemotherapy in patients with inoperable non-small cell lung cancer. 831 Oct 15

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

Carcinoma of unknown primary site (CUPS) accounts for 5-10% of all malignancies. Forty patients with metastatic CUPS or advanced oesophagogastric/pancreatic adenocarcinomas were recruited. Eligibility included ECOG performance status 0-2, minimum life expectancy of 3 months and measurable disease. The regimen consisted of bolus intravenous 5 fluorouracil (5-FU) and leucovorin (20 mg m-2) days 1-5 and carboplatin (AUC5) on day 3. The leucovorin/carboplatin/5-FU (LCF) was repeated every 4 weeks. The starting dose of 5-FU was 350 mg m-2 day-1 with escalation to 370 and then 400 mg m-2 day -1 after the toxicity at the previous level had been assessed. The maximum tolerated dose (MTD) was defined as the dosage of 5-FU that achieved 60% grade 3/4 toxicity. In addition, objective and symptomatic responses, quality of life and survival were assessed. The MTD of 5-FU in the LCF regimen was 370 mg m-2. The predominant toxicity was asymptomatic marrow toxicity. The 350 mg m-2 level was then expanded. There were two toxic deaths due to neutropenic sepsis, one at 370 mg m-2 after one course and one at 350 mg m-2 after four courses. The objective response rate was 25% with one complete response (CR) and nine partial responses (PRs). The median duration of response was 3.4 months (range 1-10). The CR and eight of the nine PRs were in CUPS patients. Twelve patients developed progressive disease on LCF. Median survival for all 40 patients was 7.8 months (10 months median survival for those treated at 350 mg m-2). The majority of patients described a symptomatic improvement with LCF chemotherapy. The recommended dose of 5-FU for future studies is 350 mg m-2 combined with leucovorin 20 mg m-2 and carboplatin (AUC5).
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PMID:A phase I/II study of leucovorin, carboplatin and 5-fluorouracil (LCF) in patients with carcinoma of unknown primary site or advanced oesophagogastric/pancreatic adenocarcinomas. 900 Jun 5

This study was performed to determine the activity and toxicity of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given by 1-hour infusion plus carboplatin in the treatment of patients with advanced non-small cell lung cancer when used in a multicenter, community-based setting. The study population included 100 chemotherapy-naive patientswith stage IIIB or IV non-small cell lung cancer, Karnofsky performance status 70 to 100, measurable disease, and adequate kidney, liver, and bone marrow function. All patients received paclitaxel 225 mg/m2 intravenously by 1-hour infusion followed immediately by carboplatin at a targeted area under the concentration-time curve of 6.0 (Calvert formula). Cycles were repeated every 21 days. Colony-stimulating factors were not used routinely. Thirty-eight (38%) of 100 patients had objective responses (38 [40%] of 94 evaluable patients) to treatment (three complete responses, 35 partial responses). Thirty-two other patients had stable disease at initial re-evaluation. Weight gain during treatment occurred in 47% of those patients with objective response or stable disease. The median survival among all 100 patients was 8 months, with a 1-year survival rate of 42%. Leukopenia was common, but hospitalization for treatment of neutropenia and fever occurred in only 3% of courses. Cumulative peripheral neuropathy occurred consistently, but usually after the third or fourth course; it was severe (grade 3) in only 15% of patients. Other grade 3 and 4 toxicity was uncommon. One patient died as a result of treatment due to sepsis. This large, multicenter, community-based phase II trial demonstrates the efficacy of paclitaxel/carboplatin combination chemotherapy in advanced non-small cell lung cancer. This regimen is relatively well tolerated and when paclitaxel is given by 1-hour infusion, this treatment is easily administered in the outpatient setting.
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PMID:Paclitaxel (1-hour infusion) plus carboplatin in the treatment of advanced non-small cell lung cancer: results of a multicenter phase II trial. 933 Nov 13

The purpose of this study was to evaluate the combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin in patients with endometrial cancer known to be resistant to standard therapy. Subjects were taken from three groups: (1) recurrent or persistent disease following surgery and/or radiation, (2) advanced disease at diagnosis, and (3) high-risk histology. The combination of carboplatin (pharmacologically dosed at an area under the concentration-time curve of 5) and paclitaxel (135 to 175 mg/m2 over 3 hours) was given intravenously every 4 weeks for eight courses. Data about response, overall and progression-free survival, and toxicity were collected. Response and toxicity were evaluated by physical examinations, x-ray films, and blood tests. Twenty patients have participated to date, including eight considered evaluable for response. Due to limited follow-up, survival and progression-free intervals are not yet assessable. Of patients with measurable disease, five of eight (63%) have had significant reduction in the size of evaluable tumor masses, constituting a partial response. Although two patients had clinical and radiographic complete responses, occult disease was found at surgery. There were no complete responders. Fifteen patients had grade 3 or 4 hematologic toxicity, but none had neutropenic fever or hospitalization for sepsis. One patient was taken off study for grade 3 neuropathy. There was one possible treatment-related death. In this preliminary report, this combination is active against tumors of the endometrium, with acceptable levels of toxicity. Further follow-up will be required to determine the duration of response and whether progression-free and overall survival are influenced by treatment with these drugs.
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PMID:A trial of outpatient paclitaxel and carboplatin for advanced, recurrent, and histologic high-risk endometrial carcinoma: preliminary report. 934 28


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