Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied escalating doses of recombinant human interleukin-1 beta (IL-1 beta) alone and after a myelosuppressive dose of 5-fluorouracil (5-FU) in patients with gastrointestinal cancer. Transient neutropenia, monocytopenia, and lymphocytopenia were observed followed by a 1.3- to 6.0-fold (mean, 3.46-fold) dose-dependent neutrophil leukocytosis (P less than .00001) on the days of IL-1 beta administration. Increases in platelet counts were observed at a median of 14 days (range, 6 to 23) after IL-1 beta administration. Transient hypoglycemia, rebound hyperglycemia, elevations in serum cortisol, and C-reactive protein were observed. Side effects included fever, rigors, and headache in the majority of patients. Hypotension was observed in three of five patients at the highest dose level (0.1 micrograms/kg) and was dose-limiting. Fewer days of neutropenia were noted after 5-FU plus IL-1 beta than after 5-FU alone; however, this difference did not reach statistical significance. These data show that IL-1 beta has stimulatory effects in human hematopoiesis.
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PMID:A phase I trial of recombinant human interleukin-1 beta alone and in combination with myelosuppressive doses of 5-fluorouracil in patients with gastrointestinal cancer. 188 14

Twenty-nine patients with measurable metastatic upper gastrointestinal cancer received dihydroxyanthracenedione (DHAD, NSC 301739) on a 5-day I.V. schedule administered every 4 weeks. Good-risk patients received DHAD at the starting daily dose of 4 mg/m2, while patients who had had therapy with radiation or myelosuppressive drugs such as mitomycin C or a nitrosourea compound received an initial daily dose of 3 mg/m2. Most of the patients had disease refractory to 5-Fu-adriamycin-mitomycin-C-containing regimens. Eight of 25 patients evaluable for response had received no prior chemotherapy. There were no complete or partial remissions in this study. Stabilization of disease occurred in six of 14 patients with gastric carcinomas and five of 10 patients with pancreatic carcinomas. The dose-limiting toxic effect was myelosuppression; neutropenia was more severe than thrombocytopenia. The myelosuppression was more severe in patients who had poor bone marrow reserve and liver function impairment. These results suggest that DHAD administered by the 5-day dose schedule as used in this study is not very effective against gastric and pancreatic carcinomas.
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PMID:Phase II evaluation of dihydroxyanthracenedione (DHAD, NSC 301739) in patients with upper gastrointestinal tumors. A preliminary report. 686 18

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of paclitaxel are reviewed. Paclitaxel is a diterpenoid taxane derivative found in the bark and needles of the western yew, Taxus brevifolia. Although it shares some structural similarities with other natural alkaloids, it contains a unique taxane ring. It is also unique in that its mechanism of action involves interruption of mitosis by promoting and stabilizing microtubule formation. Paclitaxel doses greater than 60 mg/sq m i.v. consistently produce mean peak plasma concentrations of 2-13 microM. Liver metabolism and biliary excretion are probably responsible for most of the drug's elimination. In clinical trials, paclitaxel has shown substantial activity against advanced, refractory ovarian cancer, metastatic breast cancer, and lung cancer. Paclitaxel may slow the course of melanoma and is being investigated in patients with advanced head and neck cancer and gastrointestinal cancer. Neutropenia is the major dose-limiting toxic effect of paclitaxel. Other adverse effects include hypersensitivity reactions, cardiac toxicity, and neurotoxicity. The recommended dosage for the treatment of recurrent metastatic ovarian cancer is 135 mg/sq m i.v. given over 24 hours every three weeks. It is recommended that neutrophil-count and platelet-count recovery be allowed to occur before the next treatment cycle is begun. Paclitaxel's activity against refractory ovarian cancer has not been matched since the inclusion of cisplatin in treatment regimens.
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PMID:Paclitaxel: a new antineoplastic agent for refractory ovarian cancer. 769 62

Despite the long clinical history of 5-FU in gastrointestinal cancer, the development of oral agents has been a productive endeavor, and oral fluoropyrimidine agents are likely to play an important role in the management of colorectal cancer. Results of recent trials in advanced/metastatic colorectal cancer have shown equivalence of response rates, time to disease progression, and median survival and reduced rates of neutropenia and stomatitis with oral capecitabine (Xeloda) or UFT/leucovorin compared with standard fluorouracil (5-FU)/leucovorin regimens. Evaluation of these oral agents in adjuvant therapy, in combination chemotherapy, and in combination with radiation therapy is ongoing.
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PMID:Role of oral chemotherapy in colorectal cancer. 1119 16

Anthracyclines, together with taxanes, are at present the most active agents in metastatic breast cancer, while single-agent, bolus 5-fluorouracil (5-FU) is not very active in this setting. In view of encouraging results and tolerable toxicity of continuous infusion of 5-FU in gastrointestinal cancer, innovative oral 5-FU agents such as capecitabine have been developed. Capecitabine is a prodrug that is converted into the active compound 5-FU preferentially at the tumor site. An intermittent dosing schedule of capecitabine twice daily at a dose of 2510 mg/m2/day on days 1-14 in a 3-week cycle appeared to be feasible and resulted in a high dose intensity. A large phase II study investigating capecitabine in 135 advanced breast cancer patients, pretreated with anthracyclines and taxanes, observed three complete and 24 partial responses (response rate, 20%), with a mean duration of 8.0 months. Preliminary results of a study comparing capecitabine with paclitaxel in 42 breast cancer patients failing anthracyclines indicate that the efficacy of capecitabine is comparable to that of paclitaxel, with response rates of 36% and 21%, respectively. Another study reported a response rate of 25% for capecitabine as first-line therapy for advanced breast cancer in women aged > or = 55 years, which tended to be better than combination chemotherapy with cyclophosphamide/methotrexate/5-FU. In all studies, capecitabine side effects were mainly mild, and treatment-related grade 3/4 toxicity consisted of diarrhea (8%-11%), nausea (4%-11%), hand-foot syndrome (10%-18%), neutropenia (3%-20%), and bilirubin elevation (6%). Capecitabine is clearly an active agent for the treatment of breast cancer. It is currently registered in various countries for use in third-line treatment of metastatic disease. Its further role will have to be defined from data of randomized phase III studies.
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PMID:Capecitabine in breast cancer: current status. 1189 51

The standard de Gramont (dG) regimen of fortnightly leucovorin, bolus fluorouracil and 22-h infusion of fluorouracil, d1+2, and the same regimen plus oxaliplatin, are effective but also cumbersome. We therefore present simplified 'Modified de Gramont' (MdG) regimens. Forty-six advanced gastrointestinal cancer patients entered a dose-exploring study of MdG, including an expanded cohort of colorectal cancer patients at optimum dose. Treatment (fortnightly) comprised: 2-h i.v.i. leucovorin (350 mg d,l-LV or 175 mg l-LV, not adjusted for patient surface area); bolus fluorouracil (400 mg m(-2)), then ambulatory 46-h fluorouracil infusion (2000-3600 mg m(-2), cohort escalation). Subsequently, 62 colorectal patients (25 unpretreated; 37 fluorouracil-resistant) received MdG plus oxaliplatin (OxMdG) 85 mg m(-2). Fluorouracil pharmacokinetics during MdG were compared with dG. The optimum fluorouracil doses for MdG alone were determined as 400 mg m(-2) bolus + 2800 mg m(-2) 46-h infusion. A lower dose of 400 mg m(-2) bolus + 2400 mg m(-2) infusion which, like dG produces minimal toxicity, was chosen for the OxMdG combination. Fluorouracil exposure (AUC(0-48 h)) at this lower dose is equivalent to dG. With OxMdG, grade 3-4 toxicity was rare (neutropenia 2.8% cycles; vomiting or diarrhoea <1% cycles), but despite this there were two infection-associated deaths. Oxaliplatin was omitted for cumulative neurotoxicity in 17 out of 62 patients. Objective responses in colorectal cancer patients were: 1st-line MdG (22 assessable): PR=36%, NC=32%, PD=32%. 1st-line OxMdG (24 assessable): CR/PR=72%; NC=20%; PD=8%; 2nd line OxMdG (34 assessable): PR=12%; NC=38%; PD=50%. MdG and OxMdG are convenient and well-tolerated. OxMdG was particularly active as 1st-line treatment of advanced colorectal cancer. Both regimens are being further evaluated in the current UK MRC phase III trial.
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PMID:A 'modified de Gramont' regimen of fluorouracil, alone and with oxaliplatin, for advanced colorectal cancer. 1217 75

Cisplatin is an active palliative chemotherapy agent in advanced upper gastrointestinal cancer, but it is associated with significant non-haematological toxicity. Substitution of cisplatin by carboplatin in combination chemotherapy regimens may reduce these adverse effects. These two phase II studies evaluated the efficacy and toxicity of the combination of mitomycin C (MMC) 7 mg/m2 q 6 weekly, carboplatin area under the concentration-time curve 5 mg/ml/min q 3 weekly and protracted venous infusion 5-fluorouracil (5FU) 300 mg/m2/day (McarboF) in advanced upper gastrointestinal cancer. Between October 1998 and June 2000, 31 patients were enrolled in the studies, 23 patients in the oesophago-gastric study and eight patients in the pancreatic study. Although non-haematological toxicity was modest, both protocols were closed prematurely because of excessive haematological toxicity and frequent treatment delays. The overall incidence of grade 3/4 neutropenia and thrombocytopenia was 39 and 52%, respectively. The McarboF combination showed significant activity with an overall response rate of 52% in advanced oesophago-gastric cancer. Palliative benefit was also evident with improvement in symptoms of pain and weight loss in over 79 and 50% of patients in the oesophago-gastric study and pancreatic study, respectively. Median overall survival times were 10.6 and 6.6 months for patients with oesophago-gastric and pancreatic cancer, respectively. The McarboF regimen showed promising activity in advanced upper gastrointestinal cancer, with modest non-haematological side-effects. This combination merits further evaluation with modification of the dose and schedule of carboplatin and MMC in order to reduce the severity of haematological toxicity.
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PMID:Mitomycin C, carboplatin and protracted venous infusion 5-fluorouracil in advanced oesophago-gastric and pancreatic cancer: results of two phase II studies. 1280 Oct 44

Oncologic emergencies have been extensively described and clearly defined. In oncology daily practice, cancer patients seek non-scheduled medical care in situations they perceive as a medical emergency, but which may not be a true emergency. The aim of the study was to identify the main symptoms leading to a non-scheduled consultation (NSC) and their relationship to the type of cancer, and to evaluate whether the diagnosis at discharge of patients admitted as result of a NSC correlates with a true oncologic emergency. This was a prospective observational study. Between July 2002 and April 2003, 365 NSCs were recorded. The most frequent baseline diseases were breast cancer (70), lung cancer (67), gastrointestinal cancer (52), lymphoma (42) and ovarian cancer (22). The most common symptoms for consultation were: fever (84), pain (81), cutaneous manifestations (26), dyspnea (23), bleeding (16) and abdominal distention (16). Overall, 114 of 365 NSCs (31%) resulted in admission. The most frequent symptoms resulting in admission were fever (42), pain (16), dyspnea (11), vomiting (9), neurologic manifestations (7), abdominal distention (6) and anuria (6). At discharge, only 30 patients (26%) admitted after a NSC were diagnosed with a defined oncologic emergency: febrile neutropenia (13), intestinal occlusion (12), obstructive uropathy (4) and abdominal perforation (1). True emergencies were not the most frequent causes of NSC at our institution.
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PMID:Non-scheduled consultation in oncologic patients. How many of them are true emergencies? An observational prospective study. 1473 38

Capecitabine is a highly active oral fluoropyrimidine that is an attractive alternative to 5-fluorouracil in colorectal cancer treatment. The current study, undertaken in 27 patients with gastrointestinal tumours, aimed to assess the toxicity and potential for significant pharmacokinetic interactions of a combination regimen incorporating capecitabine with 3-weekly irinotecan (XELIRI). Irinotecan (200 and 250 mg m(-2)) was administered as a 90-min infusion on day 1 in combination with escalating capecitabine doses (700-1250 mg m(-2) twice daily) administered on days 2-15 of a 3-week treatment cycle. Pharmacokinetics were characterised on days 1 and 2 of the first two cycles. A total of 103 treatment cycles were administered. The principal dose-limiting toxicities were diarrhoea and neutropenia. Capecitabine 1150 mg m(-2) twice daily with irinotecan 250 mg m(-2) was identified as the maximum-tolerated dose and capecitabine 1000 mg m(-2) with irinotecan 250 mg m(-2) was identified as the recommended dose for further study. Analyses confirmed that there were no significant pharmacokinetic interactions between the two agents. The combination was clinically active, with complete and partial responses achieved in heavily pretreated patients. This study indicates that XELIRI is a potentially feasible and clinically active regimen in patients with advanced gastrointestinal cancer.
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PMID:A phase I clinical and pharmacokinetic study of capecitabine (Xeloda) and irinotecan combination therapy (XELIRI) in patients with metastatic gastrointestinal tumours. 1575 52

Hematologic toxicities of cancer chemotherapy are common and often limit the ability to provide treatment in a timely and dose-intensive manner. These limitations may be of utmost importance in the adjuvant and curative intent settings. Hematologic toxicities may result in febrile neutropenia, infections, fatigue, and bleeding, all of which may lead to additional complications and prolonged hospitalization. The older cancer patient and patients with significant comorbidities may be at highest risk of neutropenic complications. Colony-stimulating factors (csfs) such as filgrastim and pegfilgrastim can effectively attenuate most of the neutropenic consequences of chemotherapy, improve the ability to continue chemotherapy on the planned schedule, and minimize the risk of febrile neutropenia and infectious morbidity and mortality. The present consensus statement reviews the use of csfs in the management of neutropenia in patients with cancer and sets out specific recommendations based on published international guidelines tailored to the specifics of the Canadian practice landscape. We review existing international guidelines, the indications for primary and secondary prophylaxis, the importance of maintaining dose intensity, and the use of csfs in leukemia, stem-cell transplantation, and radiotherapy. Specific disease-related recommendations are provided related to breast cancer, non-Hodgkin lymphoma, lung cancer, and gastrointestinal cancer. Finally, csf dosing and schedules, duration of therapy, and associated acute and potential chronic toxicities are examined.
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PMID:Canadian supportive care recommendations for the management of neutropenia in patients with cancer. 1831 81


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