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

The purpose of this study was to evaluate the activity and safety of oxaliplatin and protracted venous infusion of 5-fluorouracil (PVI 5-FU) in patients with advanced or relapsed 5-FU pretreated colorectal cancer. 38 patients with advanced or metastatic colorectal carcinoma with documented progression on or within 6 months following 5-FU or thymidylate synthase inhibitor containing chemotherapy were recruited between June 1997 and September 2000. Oxaliplatin (100 mg x m(-2)) was given every 2 weeks and PVI 5-FU (300 mg x m(-2) x day(-1)) was administered. Median age of patients was 61 years. 17 patients had >2 sites of disease involvement. 10 had received 5-FU based adjuvant chemotherapy. 16 received oxaliplatin and PVI 5-FU as second-line chemotherapy for advanced disease and 22 as third or subsequent lines. Median follow up was 6.1 months. The best achieved objective tumour response rate was 29% (11 partial responses 95% confidence interval [CI] = 15-46%). 20 patients (52.6%) had stable disease. The median duration of response was 3.9 months. Even for patients who had previously received both 5-FU and irinotecan (n = 22), 27.3% had partial response with oxaliplatin and PVI 5-FU. 37 patients had symptoms on entry into the study. 25 patients had pain, 10 had anorexia and 28 had lethargy. 64%, 70% and 17.9% had symptomatic improvement after treatment respectively. Grade 3-4 toxicities were anaemia 10.6%, neutropenia 2.6%, thrombocytopenia 5.2%, diarrhoea 18.9%, nausea and vomiting 2.7%, infection 5.4% and lethargy 37.8%. The median survival was 9.1 months. Probability of overall survival at 6 months was 58.4% (95% CI = 38.7-73.7%). The median failure-free survival was 4 months. Oxaliplatin and PVI 5FU is an active and well tolerated regimen in patients with heavily pre-treated advanced colorectal cancer.
 ...
PMID:Oxaliplatin and protracted venous infusion of 5-fluorouracil in patients with advanced or relapsed 5-fluorouracil pretreated colorectal cancer. 1172 Apr 58

The purpose of the study was to assess response rate, clinical outcome, organ/function preservation and toxicity in head and neck cancer patients treated with induction chemotherapy followed by concomitant chemoradiotherapy and, when necessary, limited surgery. The study design was a phase II non-randomized trial in hospitalized patients setting. The treatment plan consisted of 3 cycles of induction chemotherapy with cisplatin, fluorouracil (5-FU), l-leucovorin and interferon alpha2b (PFL-IFN) followed by 7 cycles of 5-FU, hydroxyurea and concomitant radiation for 5 days (FHX) for a total radiation dose of 70 Gy. 13 Cis-retinoic acid was added to treatment regimen for chemoprevention and a systematic prophylaxis of mucositis was administered to all patients during FHX. Conservative surgical resection was reserved to patients with no optimal response (PR > or =70%), whereas radical surgery was performed as salvage treatment. Twenty-six patients were treated at one institution: more than 90% had stage IV disease and only 19.2% had laryngeal cancer. Eighty-one percent of patients had performance status 0 and 23.1% of patients had >5% weight loss at the start of treatment. Nineteen patients were analyzed for response to PFL-IFN: 3/19 (15.8%) patients achieved a CR and 7/19 (36.8%) achieved a PR for an ORR of 52.6%. FHX was administered on protocol to 12 patients: 6 patients (50%) had CR, 1 patient (8.3%) had PR for an ORR of 58.3%, 2 patients (16.7%) had SD and 3 patients (25%) had PD. At the completion of FHX, no patient underwent local therapy according to treatment plan. At a median follow-up time of 13.5 months (range 1-28+) at June 2001, among 26 patients enrolled 12 (46.1%) were still alive and 9 (75%) of them were progression-free. The median duration of response was 9 months (range 0-25+), the median progression-free survival was 10.5 months (range 0-28+), the median overall survival time was 9 months (range 1-22). The toxicity was significant and consisted mainly of mucositis and, to a lesser extent, neutropenia/thrombocytopenia. In the present study, the low serum levels of leptin and the high serum levels of proinflammatory cytokines in advanced stage cancer patients were confirmed. In conclusion, this sequential induction chemotherapy and chemoradiotherapy program has been found moderately active and significantly toxic; moreover, the long overall treatment duration must be taken into consideration. For these reasons, this regimen could not be recommended for a phase III randomized study.
 ...
PMID:Induction chemotherapy followed by concomitant chemoradiation therapy in advanced head and neck cancer: a phase II study for organ-sparing purposes evaluating feasibility, effectiveness and toxicity. 1178 11

Docetaxel is an excellent agent with a high antitumor effect for advanced/recurrent head and neck cancer. A 67-year-old male with advanced hypopharyngeal cancer (T3N2bM1: Stage IV) underwent two courses of superselective intra-arterial infusion of docetaxel and intravenous administration of CDDP and 5-FU. Using a coaxial technique, a microcatheter was placed in the feeding artery. Using imaging techniques docetaxel (60 mg/body and 30 mg/body) was infused into the vessels. During chemotherapy the patient received concomitant radiotherapy (50 Gy). MRI after chemoradiation showed a complete response for the primary tumor and a partial response for the neck metastasis. Grade 4 leukopenia and neutropenia and grade 3 pharyngitis/esophagitis were observed during chemoradiotherapy, but these adverse effects abated immediately and were not critical. We conclude that this superselective intra-arterial infusion of docetaxel will be useful and safe for head and neck cancer.
 ...
PMID:[A case of advanced hypopharyngeal carcinoma successfully treated with superselective intra-arterial infusion of docetaxel]. 1186 43

Docetaxel (Taxotere) has been successfully investigated in the therapy for advanced gastroesophageal tumors as both a single agent and in combination regimens. As a single agent, phase II study results demonstrate an overall response rate of 17% to 24%, with occasional complete responses in a disease in which complete responses are rare. These figures classify docetaxel among the most active agents for the disease. Further research initiatives in gastric cancer have evaluated the combined use of docetaxel with traditionally established agents, such as cisplatin and fluorouracil (5-FU). The rationales for the combined use of docetaxel with these agents include the in vitro demonstration of a lack of complete cross-resistance and nonoverlap-ping side-effect profiles. Phase II study results of docetaxel-based combinations demonstrate high overall response rates and progression-free survival, comparable with results obtained with established three- and four-drug regimens. Therapy is generally well tolerated, with a predominant toxicity of hematologic neutropenia. Docetaxel-based combination regimens are currently undergoing evaluation in randomized phase III trials in comparison with established standard regimens. While previous combination chemotherapy regimens have failed to improve survival over single-agent therapy, the aim for incorporation of docetaxel with other active agents is to improve palliation and possibly survival of patients with gastric cancer.
 ...
PMID:Docetaxel for gastric and esophageal carcinomas. 1210 2

TS-1 is a novel oral anticancer drug that is a formation of 5-FU. It consists of tegafur, CDHP (which inhibits 5-FU degradation enzyme), and Oxo (which reduces gastrointestinal toxicities) for an increased anticancer effect. We applied individual TS-1 therapy in 22 cases (cs) of inoperable gastric cancer and studied the clinical and adverse effects. Patients were treated with daily oral administration of 80-100 mg TS-1 for 4 weeks, followed by a rest for 1 or 2 weeks. The response rate was found to be 27.3% (6/22) (PR: 6 cs, NC: 4 cs, PD: 10 cs, NE: 2 cs). Overall, the median survival time was 8.2 months and the one-year survival rate was 23.6%. By location, the response rate of the primary lesion was 27.3% (6/22), abdominal lymph node metastasis 18.8% (3/16), and liver metastasis 33.3% (4/12). There was no significant difference in the response rate by tissue type. A comparison by whether or not patients had undergone previous chemotherapy revealed a response rate of 37.5% (6/16) in patients who had undergone previous chemotherapy, and 0% (0/6) in those who had not. The prevalence of adverse effects was 68.2% (15/22), with the main adverse effects being myelosuppression, pigmentation and appetite loss. However, adverse effects with a grade of more than 3 occurred in only one case of neutropenia. We could observe the course of all patients on an outpatient basis.
 ...
PMID:[Clinical study of individual TS-1 therapy for inoperable gastric cancer]. 1214 96

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.
 ...
PMID:A 'modified de Gramont' regimen of fluorouracil, alone and with oxaliplatin, for advanced colorectal cancer. 1217 75

Topotecan is a topoisomerase-I inhibitor, a drug that stabilizes a covalent complex of enzymes and causes strand cleavage of DNA. 5-Fluorouracil (5FU) is an antimetabolite that interferes with DNA synthesis. Preclinical studies using human cancer cell line models have shown potential therapeutic synergy between these two drugs by showing the maximum cytolytic effect using sequential 5FU followed by topotecan. In the current study, 5FU was used at a fixed dose of 375 mg/m2 given intravenously for five consecutive days on a 28 day cycle. Topotecan was dose-escalated in cohorts of patients from 0.5 to 1.0 mg/m2 given intravenously for 5 days after the 5FU dose. Eleven patients were entered at different dose levels. Both hematological and gastrointestinal toxicity were dose limiting. Diarrhea was the dose-limiting toxicity at the dose of 0.75 mg/m2 of topotecan. Two cases of grade 4 neutropenia were also observed at this dose level. One patient with small cell lung cancer had a complete response, while one patient with metastatic colorectal cancer had a partial remission. Three other patients had stable disease, lasting between 6 and 8 months. Overall, the regimen was well tolerated. A phase II study using a dose of 5FU at 375 mg/m2 followed by topotecan at 0.75 mg/m2 intravenously over 5 days every 28 days is recommended.
 ...
PMID:Phase I study of sequential administration of topotecan and 5-fluorouracil in patients with advanced malignancies. 1219 19

Recently chemoradiotherapy for esophageal cancer has been drawing public attention to the issue of quality of life maintenance for patients. Although the standard method of chemoradiotherapy is CDDP/5FU, it has been claimed that CDGP (a derivative of CDDP) alone is more effective than CDDP for the treatment of esophageal cancer due to its low nephro- and digestive toxicity. We used a small amount of CDGP/5-FU in combination with radiation instead of CDDP, for the treatment of esophageal cancer and performed clinical examination of patients. The partial response rate was 80% and the complete response rate was 50%. Major side-effects were leukopenia, neutropenia, thrombocytopenia and anemia. Further study of dosage and schedule is necessary, however, CDGP/5-FU combined with radiation therapy could be used as choices of chemoradiotherapy for esophageal cancer in the future.
 ...
PMID:[Clinical study of the combination of small amount of nedaplatin (CDGP)/5-FU with radiation for the treatment of esophageal cancer]. 1241 54

The objective of this study was to demonstrate how a clinical practice database can be used to illustrate the variations in adjunctive chemotherapy for breast cancer, to describe a measure of dose intensity (DI) to monitor that variation, and to design interventions to maximize a full-planned dose. An arbitrary sample of oncology practices across the United States was selected, each providing data on 10-20 patients treated with adjuvant chemotherapy for early-stage breast cancer. Data on 17,566 patients from 1,438 sites were collected, consisting of patient characteristics including age, number of positive nodes, planned and delivered chemotherapy agents, and a sample of absolute neutrophil or white blood cell counts by cycle. Mean age of the patient cohort was 48.5 years, and 54% of patients were below the age of 49. Treatment for the disease has changed during the 2 periods studied, 1983-1994 and 1995-1999. Use of Adriamycin/Cytoxan (AC) increased, whereas use of Cytoxan/Adriamycin/Fluorouracil (CAF) and full-dose Cytoxan/Methotrexate/Fluorouracil (CMF1) decreased. However, the less intense Cytoxan/Methotrexate/Fluorouracil combination (CMF2) has seen an actual increase in use during the 2 periods. Within the context of oncology care, including chemotherapy, full-dose intensive therapy and cure has always been the ultimate goal. In this study only 10% of the patients given AC received less than 85% of the full referenced dose, whereas about 20% of those receiving the other combinations fell into this category. Also, the summation dose intensity (SDI), a measure tying level of dose to survival, was highest in the AC group and lowest in the CMF2 group. Dose delays and dose reductions appear to account for the decrease in DI in the CMF1, CMF2, and CAF groups. DI, particularly SDI of adjuvant chemotherapy, which ties level of dose to survival in breast cancer patients, appears to be a reliable measure with which to assess the quality of care in community oncology practices. The 2 measures presented in this paper may be useful to managed care organizations for monitoring quality outcomes in this serious disease. Because one of the major reasons for reduction in chemotherapy dose appears to be neutropenia and its complications, these organizations can establish programs using DI as a basis for developing guidelines to optimize the clinical benefits of growth factors.
 ...
PMID:Chemotherapy dose intensity determination as a quality of care measure for managed care organizations in the treatment of early-stage breast cancer. 1248 37

Capecitabine (Xeloda) is an oral prodrug that is enzymatically converted to fluorouracil (5-FU) within cancer cells. Data from two large phase III trials performed in patients receiving first-line chemotherapy for metastatic colorectal cancer showed that capecitabine yielded higher objective response rates and equivalent median time to tumor progression and overall survival rates as 5-FU/leucovorin. In these studies, capecitabine demonstrated lower rates of diarrhea, stomatitis, nausea, and severe neutropenia than bolus 5-FU/leucovorin, but a higher rate of hand-foot syndrome and hyperbilirubinemia. The natural extension of this work has been to evaluate substitution of capecitabine for 5-FU/leucovorin in combination chemotherapy trials with irinotecan (CPT-11, Camptosar) or oxaliplatin (Eloxatin). This is especially important due to concerns regarding toxicities observed with regimens that combine bolus 5-FU/leucovorin with irinotecan or oxaliplatin. Phase I/II and phase II trials of capecitabine in combination with irinotecan or oxaliplatin in patients with advanced disease indicate that the combinations are well tolerated and produce response rates that are in the range of those that would be expected with infusional 5-FU/leucovorin combined with irinotecan or oxaliplatin. Phase III trials have been initiated in the advanced disease and adjuvant settings and should help determine the efficacy, toxicity, and tolerability of the capecitabine/irinotecan or capecitabine/oxaliplatin combination in direct comparison to intravenous 5-FU/leucovorin and irinotecan or oxaliplatin.
 ...
PMID:Current status of capecitabine in the treatment of colorectal cancer. 1252 Jun 35


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>