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)

A randomized comparative study of surgical adjuvant chemotherapy using dl-leucovorin (dl-LV) and 5-fluorouracil (5-FU) (FL-therapy) with CDDP, 5-FU, and dl-LV (PFL-therapy) was conducted. The following were the administration schedules: Arm A was 13 mg/m2 of CDDP, 300 mg/m2 of 5-FU, and 30 mg/body of dl-LV for 5 consecutive days and arm B was 300 mg/m2 of 5-FU and 30 mg/body of dl-LV for 5 consecutive days. Both regimens were followed by biweekly administration of the same dose of dl-LV and 5-FU in outpatients. Arm A was started at the 26th postoperative day and arm B at the 21st day on average. Some 26 cases composed of 11 cases of arm A and 15 cases of arm B completed the administration schedules. Only one case in arm A was complicated by local recurrence around 35 months after operation. Major toxicities were anorexia and neutropenia. Both toxicities were seen more in arm A than in arm B, showing complete recovery in all cases. These data suggest that PFL-therapy and FL-therapy seem to be possible and promising surgical adjuvant therapies for advanced colorectal carcinoma.
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PMID:[A randomized comparative study of surgical adjuvant chemotherapy using 5-fluorouracil and dl-leucovorin with CDDP 5-FU and dl-leucovorin for colorectal cancer]. 917 May 24

The antineoplastic agent mitoxantrone in combination with a corticosteroid (either prednisone or hydrocortisone) has shown clinical efficacy as palliative treatment for a proportion of patients (about 35 to 40%) with hormone-resistant advanced prostate cancer, a disease which predominantly affects elderly men and for which few systemic treatment options are available. Palliative end-points including pain relief, decreased analgesic use and reduced prostate specific antigen levels (a marker of tumour response) are reached in a greater percentage of patients receiving combination therapy than corticosteroid alone. In addition, there are generally greater improvements in quality-of-life parameters in mitoxantrone recipients. However, combined treatment offers no survival advantage over corticosteroid monotherapy. Neutropenia is the most common toxicity associated with mitoxantone therapy and may necessitate dosage reduction in some patients. Otherwise, mitoxantrone generally has a more favourable tolerability profile than has been established for other cytotoxic agents such as doxorubicin with regard to acute adverse events (e.g. nausea/vomiting, anorexia, constipation, alopecia, malaise/ fatigue, oedema) and cardiac toxicity. In conclusion, administration of mitoxantrone plus a corticosteroid can provide palliation for some elderly patients with hormone-resistant advanced prostate cancer, and is thus a valuable first-line treatment for this indication.
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PMID:Mitoxantrone. A review of its pharmacology and clinical efficacy in the management of hormone-resistant advanced prostate cancer. 920 52

An early Phase II study with TUT-7 (menogaril), a new anthracycline antitumor antibiotic, was conducted in patients with various malignant tumors at 81 departments of 65 institutions nationwide. One course of TUT-7 treatment consisted of seven (7) or fourteen (14) consecutive days of administration at 75 or 100 mg/body/day with two-week drug withdrawal; at least two courses of treatment were given in principle. Among the 165 patients registered, 145 patients were eligible and 128 patients were evaluable for antitumor efficacy. In 11 patients with malignant lymphoma, one (1) had CR and five (5) had PR (54.5%); in three (3) patients with prostate cancer, one (1) had PR (33.3%); and in 12 patients with uterine cervical cancer, two (2) had PR (16.7%). Adverse drug reactions frequently observed were digestive organ disorders (anorexia and nausea/vomiting) and malaise. The abnormality in laboratory tests observed frequently was myelosuppression (leukopenia and neutropenia).
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PMID:[TUT-7 early phase II clinical study for various solid tumors and hematologic malignancies]. 927 44

Gemcitabine is a novel nucleoside analog with unique activity against a wide range of solid tumors. We initiated a multicenter phase II study in patients with non-small cell lung cancer (NSCLC) to evaluate the efficacy and safety of gemcitabine. Eligible patients had stage III and IV, previously untreated with chemotherapy, age range from 18 to 80 years, and ECOG performance status 0 2. Gemcitabine was administered at 1000 mg/m2 as a continuous i.v. infusion once a week for a consecutive 3 week period, followed by 1 week of rest. Of the 69 patients enrolled, 67 patients were eligible for efficacy evaluation. The overall response rate was 20.9% with a 95% confidence interval of 11.9-32.6%. The median survival time was 9.0 months and the 12 month survival rate was 31.3%. Grade 3 or 4 toxicities included neutropenia in 22.7%, anemia in 13.4%, leukopenia in 10.4%, anorexia in 10.4%, malaise in 7.5% and nausea/vomiting in 6.0%. Serious toxicities were septic shock and interstitial pneumonia (one patient each). Gemcitabine, administered weekly for three consecutive weeks followed by 1 week of rest, is an active agent for NSCLC. Gemcitabine is currently being evaluated in combination with cisplatin and other agents.
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PMID:Activity of gemcitabine in the treatment of patients with non-small cell lung cancer: a multicenter phase II study. 930 May 71

To assess the efficacy and toxicity of an outpatient combination chemotherapy in small-cell lung cancer (SCLC), we treated 70 consecutive patients with epirubicin 80 mg m(-2) i.v. on day 1 and etoposide 200 mg o.d. p.o. on days 1-4 (EE) at 3-weekly intervals. The median age of patients was 64 years (range 39-84). The male-female ratio was 42:28 and 35 (50%) had metastatic disease. Fifty-seven patients were evaluable for response. The overall response rate was 64.4%, including 14 (23.7%) complete responses and 24 (40.7%) partial responses. Median time to progression was 7 months in responders and 8 months in patients with limited disease. The median survival in patients with limited disease was 10.5 months (range 0.5-70 +) and 7 months (range 0.5-24) in those with extensive disease. Improvement of symptoms occurred in 79% of patients with shortness of breath, 80% with cough, 81% with haemoptysis and 68% with pain. In 19 patients an increase in body weight was noted. Major (WHO grade 3/4) toxicities were neutropenia in 13 (18.5%) patients, alopecia in 33 (47.1%) patients, mucositis in 15 (21.4%) patients, anorexia in eight patients (11.4%), nausea and vomiting in six patients (8.5%) and diarrhoea in 4 (5.7%) patients. In conclusion, EE is an active and well-tolerated outpatient regimen in the treatment of SCLC. The survival data in this unselected group of patients were disappointing and the possible explanations for this are discussed.
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PMID:Outpatient treatment with epirubicin and oral etoposide in patients with small-cell lung cancer. 930 64

CI-980 is a synthetic mitotic inhibitor that binds to the colchicine binding site of tubulin. It demonstrates broad activity against human and murine tumor models and shows no cross resistance with tumor models whose mechanism of resistance is mediated by P-glycoprotein (MDR-1). A phase I study was completed in 25 patients with solid tumors using a 24-hour infusion schedule, with courses repeated every 3 weeks. Eight dose levels were tested between 1.2 and 15.6 mg/m2. The maximum tolerated dose was 14.4 mg/m2. Neutropenia was dose-related but not dose-limiting; thrombocytopenia was infrequent. CNS toxicities were dose-limiting and consisted of dizziness, headache, loss of coordination, loss of consciousness, nervousness, and other symptoms. These events occurred near the end of the infusion and were reversible, usually within 24 hours. One patient who was to be treated at dose level 8 (intended dose was 19.2 mg/m2; actual dose was 15.6 mg/m2) became encephalopathic prior to completion of the infusion. Other adverse events included gastrointestinal toxicities (nausea, vomiting, anorexia, constipation, stomatitis, dyspepsia, bleeding, cheilitis), IV site erythema, fever, and fatigue. A partial response was observed in one patient with colon cancer and reductions in CA-125 levels were observed in 2 patients with ovarian cancer. Pharmacokinetics were linear and dose-proportional. Results indicate high systemic clearance and wide tissue distribution. Mean pharmacokinetic parameter values: T1/2 = 5.52 hours, plasma clearance 1163 mL/min/m2, and Vdss 376 L/m2.
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PMID:A phase I trial and pharmacokinetic evaluation of CI-980 in patients with advanced solid tumors. 938 46

Combined use of 5-fluorouracil (5-FU) and cisplatin has proven to have synergistic effects in many experimental systems and clinical studies. UFT, an oral preparation of uracil and tegafur in a 4:1 molar ratio, was reported to have enhanced activity as compared with 5-FU or tegafur alone against various human tumors. Based on those results, we conducted a pilot study to confirm the feasibility and antitumor effect of UFT in combination with cisplatin in patients with advanced non-small cell lung cancer (NSCLC). UFT was orally administered at a dose of 400 mg/m2 according to a protocol for step-wise prolongation of the administration period, such as days 1-14 in step I, days 1-21 in step II, days 1-28 in step III. During to course, cisplatin was administered at a fixed dose of 20 mg/m2/day on days 8 through 12. The course was repeated every 4 weeks. Numbers of patients enrolled in steps I, II, III were six, ten and six (a total of 22), respectively. There were three females and 19 males, PS scored 0/1/2 = 7/14/1, stage IIIA/IIIB/IV = 3/8/11. Adenocarcinoma/squamous cell carcinoma/large cell carcinoma = 11/7/4, and median age 68 (range 52-79). All 22 patients were evaluable for toxicity, and 21 for efficacy. Compliance of UFT declined as the administration period of UFT was prolonged. In step I, one patient had grade 3 toxicity of each neutropenia, thrombocytopenia, nausea/vomiting and diarrhea. In step II, grade 3, 4 neutropenia was seen in four patients, grade 3 thrombocytopenia and anorexia in one patient, and grade 3 nausea/vomiting in four patients. In step III, there was grade 3 neutropenia in two patients and grade 3 anorexia in one patient. All other toxicities were mild. The overall response rate was 38% (one CR and 7 PR, 95% C.I.: 21-59%). Combination therapy with oral UFT and 5-day infusion of cisplatin is feasible with substantial antitumor effect against advanced NSCLC. Since UFT compliance decreased in step III (no patient in step III received > 2 courses of treatment), we considered the step II schedule to be worth for further evaluation in a combination phase II study.
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PMID:Pilot study of UFT combined with 5 consecutive days cisplatin in non-small cell lung cancer. 944 49

The effects of indomethacin, a cyclooxygenase inhibitor, upon plasma concentrations of prostaglandin E2 (PGE2), the febrile response, and metabolic and hematological alterations induced by lipopolysaccharide (LPS) were studied. Experimental endotoxemia was provoked via i.p. injection of 1.0 mg E coli LPS/kg in rats (group A). Indomethacin was introduced/os (2.5 mg/kg) 30 min prior to LPS challenge (group B). Pretreatment with this medication completely inhibited the hyperthermic response to LPS and eliminated the LPS-induced non-specific symptoms of anorexia, adipsia, reduced locomotory activity and gastrointestinal troubles. Plasma PGE2 concentrations increased as early as the 2nd h after the LPS challenge but were blocked when endotoxin application was preceded by indomethacin treatment. Indomethacin did not significantly influence hematological parameters. The dynamics of hematocrit and erythrocyte counts were similar in both groups with a decrease up to the 2nd h followed by an increase to maximum at post-treatment day 3. Pretreatment with indomethacin did not influence the endotoxin-induced leukopenia observed at the 2nd h or the accompanying neutropenia and left shift. Cyclooxygenase inhibition affected total protein concentrations; they were decreased in the early hours of the study (hours 4-6) in both groups. The later tendency towards increase in total protein concentrations was more expressed in animals from group B. Changes in blood glucose were characterized by a permanent tendency towards decrease after hour 2 of LPS challenge up to day 6 (group A). In group B, a similar tendency was observed, but glucose concentrations decreased between hours 2-6 and then returned to initial values.
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PMID:Effects of indomethacin on lipopolysaccharide-induced plasma PGE2 concentrations and clinical pathological disorders in experimental endotoxemia. 946 1

GI1147211 is a 7-substituted 10,11-ethylenedioxy-20(S)-camptothecin analogue that inhibits the nuclear enzyme topoisomerase I. In this Phase I and pharmacological study, 24 patients with advanced solid malignancies received a total of 72 courses of GI147211 as a 30-min infusion daily for 5 consecutive days, at doses ranging from 0.3 to 1.75 mg/m2/day. Severe neutropenia precluded dose escalation above 1.5 mg/m2/day in minimally pretreated patients, and both severe neutropenia and thrombocytopenia were dose limiting in heavily pretreated patients at doses above 1.0 mg/m2/day. These doses are, therefore, recommended for subsequent Phase II evaluations of GI147211 in patients with comparable prior therapy. Nonhematological toxicities, including nausea, vomiting, fatigue, and anorexia, were mild to moderate. The disposition of GI147211 in blood was described by a linear three-compartment model, with renal elimination accounting for only 11% of drug distribution. No relationship was observed between the pharmacological exposure to GI147211 and effects on neutrophils; however, patients who developed dose-limiting myelosuppression did experience greater exposure to both the lactone and total forms of the drug. The hydrolysis kinetics of GI147211 revealed not only a shift of the drug to the inactive carboxylate form in human serum albumin but also stabilization of the lactone in erythrocytes, perhaps accounting for the observed lactone:total area under the concentration-time curve ratio of 0.27. These results indicate that GI147211 exhibits predictable toxicities and that further studies are warranted to determine the distinct role of this compound among currently available camptothecin analogues.
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PMID:Phase I and pharmacokinetic study of GI147211, a water-soluble camptothecin analogue, administered for five consecutive days every three weeks. 953 26

Forty-three patients with myelodysplastic syndromes (MDS) received treatment with oral etoposide 50 mg/day for 21 consecutive days every 4 weeks. Eighteen patients (42%) experienced hematological responses, including 12 of 17 (70%) patients with chronic myelomonocytic leukemia (CMML). Three of five CMML patients who failed treatment with hydroxyurea experienced major hematological responses with oral etoposide. Median response duration exceeded 9 months (range: 4-49 + months), and one patient remains in an unmaintained complete remission for 4 years. Toxicity included nausea/vomiting in five patients, fever (four patients), infection (three patients), mucositis (two patients), and anorexia (two patients). Two patients had grade 4 neutropenia with sepsis necessitating treatment withdrawal. We conclude that low-dose oral etoposide has remitting activity in MDS and is an effective treatment alternative for patients with CMML.
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PMID:Treatment with low-dose oral etoposide in patients with myelodysplastic syndromes. 958 73


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