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)

The lack of decisive progress in ovarian cancer chemotherapy in recent years led the ARTAC "Ovary" group to initiate a study based on the hypothesis of collateral sensitivities. In this phase I-II trial, NHO-88, the V-H combination (associating vinorelbine (VNB) and hexamethylmelamine (HMM) was studied in patients with advanced ovarian adenocarcinomas, most of which had become resistant to previous chemotherapy. The aim of the study was to find an active combination without complete cross resistance with first-line platinum salt based combinations, such as CAP, FAP or CACb-300. A pilot feasibility study was first carried out to determine the maximum tolerated weekly dose (MTWD) of VNB (20 mg/m2/week), HMM being administered per os on days 1-14 of every 28-day cycle at a standard dose of 250 mg/m2/day. An open phase II-A study was further carried out according to a 2-step sequential analysis method for phase II clinical trials. We observed: 1), a good tolerance of the V-H combination apart from frequent neutropenia; 2), a response rate of 35% (95% confidence interval: 23-47%); 3), a median response duration of 4 months (range: 1-7 months); 4), in some cases, the absence of a complete cross-resistance between the V-H regimen and the previously administered platinum-based combinations. These results, which are currently being validated (phase II-B ongoing), constitute the first step in the search for active systems of sequential or alternate chemotherapeutic regimens for the treatment of advanced carcinomas.
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PMID:[Study of vinorelbine (V) combined with hexamethylmelamine (H) (combination V-H) in adenocarcinoma of the ovary: results a phase I-IIA trial, NHO-88, of ARTAC "ovarian" group]. 178 25

The influence of cytotoxic chemotherapy on the number and function of peripheral neutrophils was studied in time sequence in 9 cancer patients; 6 patients with transitional cell carcinoma of urothelium treated with CAP, the combination of cyclophosphamide, adriamycin and cisplatin, and the other 3 with testicular tumor treated with PEB, the combination of cisplatin, etoposide and bleomycin. The neutrophil function was evaluated by the superoxide production, measuring chemiluminescence of the neutrophil suspension by a photometer. The peripheral neutrophil count (PNC) significantly (p < 0.01) decreased with the nadir count of 280 +/- 100/mm2 16.4 days after cytotoxic chemotherapy and recovered to the normal level by the next course. The neutrophil function declined significantly (p < 0.01) as PNC decreased, reached the minimum almost at the same time as PNC, and returned to the normal level by the next course. Of the 9 cases, the neutrophil function in 6 cases reached the minimum on the same day as that of PNC. The study shows that cytotoxic chemotherapy appears to impair the host defense mechanism in cancer patients not only in inducing neutropenia but also in deteriorating neutrophil function at the same time.
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PMID:[Influence of cytotoxic chemotherapy on superoxide production by neutrophils in cancer patients]. 768 Jul 4

The in vivo effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the number and function of peripheral neutrophils were studied in time sequence in 9 cancer patients receiving anticancer cytotoxic chemotherapy; 6 patients with transitional cell carcinoma of urothelium treated with CAP (the combination of cyclophosphamide, adriamycin and cisplatin) and the other 3 with testicular tumor treated with PEB (the combination of cisplatin, etoposide and bleomycin). The neutrophil function was evaluated by superoxide production, measuring chemiluminescence of the neutrophil suspension by a photometer. In the 1st course, when no rhG-CSF was administered, the neutrophil function declined significantly (p < 0.01) as the peripheral neutrophil count (PNC) decreased, reached the minimum almost at the same day as PNC reached the nadir, and returned to the normal level at the beginning of the next course. In the 2nd course, when rhG-CSF (75 micrograms/body) was administered subcutaneously daily for 14 consecutive days beginning at 72 hours after the chemotherapy, the nadir of neutropenia was elevated (p < 0.01), the period of neutropenia (< 1,000/mm3) was shortened (p < 0.01), the recovery from neutropenia (> 1,500/mm3) was accelerated (p < 0.01) as compared to the 1st course, and an marked increase of PNC (p < 0.01) to the peak on the next day of the last administration of rhG-CSF was observed. In addition, deterioration of neutrophil function was alleviated (p < 0.05) and the neutrophil function was enhanced (p < 0.01-0.05) during rhG-CSF administration, even at the nadir of neutropenia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effects of recombinant human granulocyte colony-stimulating factor on superoxide production by neutrophil in cancer patients receiving chemotherapy]. 768 23

alpha-Interferon (IFN-alpha) enhances the activity of 5-fluorouracil in patients with advanced colorectal carcinoma. Preclinical evidence suggests a similar potential role for IFN-alpha combined with cyclophosphamide, doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH), and 5-fluorouracil (CAF) in advanced adenocarcinoma of the breast. To determine a maximum tolerated dose of IFN-alpha that could be combined with CAF and that did not compromise CAF dose intensity and to determine the effect of IFN-alpha on the pharmacokinetics of doxorubicin, a phase I study of IFN-alpha plus CAF was performed by the Eastern Cooperative Oncology Group. Nine patients with advanced breast cancer received CAF (cyclophosphamide at 100 mg/m2/day p.o. on days 1-14, doxorubicin at 30 mg/m2 and 5-fluorouracil at 500 mg/m2 i.v. bolus on days 1 and 8) plus IFN-alpha (1 milliunit/m2, n = 6, or 2 milliunits/m2, n = 3) given s.c. on days 1, 3, 5, and 8 (1 h prior to the doxorubicin and 5-FU injection on days 1 and 8) of each cycle every 28 or more days. Escalation of the IFN-alpha dose occurred in cohorts of 3-6 patients if a dose-limiting toxic event (neutropenic fever, platelet nadir of < 25,000/microliters, > 2-week treatment delay, or a > 50% dose reduction in day 8 CAF) occurred during the first two cycles in 0 of 3 or 1 of 6 patients. During cycle 1, IFN-alpha was omitted on day 1, and multiple plasma samples were drawn on day 1 (without IFN-alpha) and day 8 (with IFN-alpha) after each doxorubicin injection and were analyzed for plasma doxorubicin concentration. The maximum tolerated dose of IFN-alpha by our criteria was 1 milliunit/m2, and neutropenia was the predominant toxic effect that precluded IFN-alpha dose escalation. The dose intensity of CAF achieved with IFN-alpha was identical to that for CAF alone observed in prior studies. IFN-alpha had no significant effect on the pharmacokinetics of doxorubicin, although 3 of 7 patients studied had reduced doxorubicin clearance, ranging from 32% to 69%. Alternative CAF drug delivery schedules (all drugs given i.v. every 3-4 weeks) that are more amendable to hematopoietic growth factor support may be more suitable to combine with higher doses of IFN-alpha that may produce modulation.
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PMID:Phase I trial of cyclophosphamide, doxorubicin, and 5-fluorouracil plus interferon-alpha 2b in patients with advanced breast cancer. 833 55

A large study of tumors of low malignant potential confirmed the favorable survival in this group of patients compared to invasive epithelial ovarian tumors. Only 8% of patients died with recurrent disease after surgery. Patients with stage IA borderline tumors with mucinous histology tended to recur later and carried a poorer prognosis than patients with serous histology and similar stage. The group at highest risk for relapse were age greater than 70, stage II or III tumors, and histology other than serous. Long-term survival in this group was less than 75%. This high-risk group of patients should be targeted for innovative adjuvant treatment strategies. This year several well-designed studies with large sample sizes showed DNA ploidy to be an important new independent prognostic factor in stage I ovarian carcinoma. In patients with well-differentiated early stage ovarian cancer, DNA flow cytometric analysis may indicate subgroups with less favorable prognostic characteristics. This method of analysis may be beneficial in determining the need for additional treatments after surgery for early stage ovarian carcinoma. Recommendations for the definitive management of early stage ovarian cancer awaits completion of current GOG and European randomized prospective studies. Paclitaxel given in combination with platinum-containing agents is an intense area of research for treatment of advanced stage disease. Early data from a prospective randomized trial of patients with advanced ovarian cancer showed a higher response rate and longer disease-free survival in patients treated with paclitaxel and cisplatin compared to a standard regimen of cyclophosphamide and cisplatin. The impact of this treatment on long-term survival awaits maturation of data. Preliminary results evaluating G-CSF in combination with paclitaxel and cisplatin for dose escalation was reported. Paclitaxel, 250 mg/m2, and cisplatin, 75 mg/m2, were the maximally tolerated doses, with peripheral neuropathy or myalgias the dose limiting toxicities. Further studies are now underway to test the effect of dose-response with escalation therapies and to determine the optimal dose and schedule for the management of patients with advanced ovarian cancer. IL-3 significantly ameliorated neutropenia but did not prevent cumulative platelet toxicity in a regimen utilizing high-dose carboplatin. This mild improvement in myelosuppression was obtained at the cost of significant toxicity. Nausea, vomiting, malaise, bone pain, headache, fever, chills and facial flushing were frequent. Intraperitoneal chemotherapy was tested as a means of consolidation treatment for patients after having a negative second-look laparotomy. These treatments were shown to be feasible; however, prospective randomized trials will be necessary to determine a benefit over operative therapy alone. Several studies addressed to problem of residual disease after primary surgery and adjuvant chemotherapy. A large phase II study conducted by the GOG confirmed the activity of salvage cisplatin-based intraperitoneal chemotherapy in patients with small-volume residual ovarian cancer with favorable pretreatment characteristics. Whether intraperitoneal platinum-based therapy represents an advantage over systemic platinum therapy is being addressed in a prospective SWOG study. The use of six additional cycles of CAP for treatment of residual disease after primary treatment of surgery and adjuvant chemotherapy did not significantly improve complete pathological response and survival. Prolonged duration of chemotherapy above six cycles is not likely to impact treatment for residual disease. A regimen of high dose carboplatin was compared to whole abdominal radiotherapy for treatment of residual disease after initial chemotherapy. There was no difference in survival or disease-free survival between treatments.(ABSTRACT TRUNCATED)
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PMID:Gynecological malignancies. 863 1

In Japan, 5-FU/5-FU derivatives or the combination therapy of CAF (cyclophosphamide, CPA; adriamycin, ADM; 5-fluorouracil; 5-FU) have been commonly used for the adjuvant treatment of breast cancer. Recently, a combination of CEF (CPA; Epirubicin, EPI; 5-FU) has come to the stage of adjuvant setting, because the cardiotoxicity was reduced in EPI. In this study, we investigated the feasibility of 6 cycles of CEF (CPA 700 mg/m2, EPI 70 mg/m2, 5-FU 700 mg/m2; day 1 iv every 3-4 weeks) in the adjuvant treatment of primary breast cancer patients with nodal involvements. All 12 patients completed 6 cycles of CEF within 8 months. The median treatment duration was 6.2 months. More than Grade III side effects of neutropenia, nausea/vomiting and alopecia were observed in 7/12 (58.3%), 5/12 (41.7%) and 12/12 (100%), respectively. No serious side effects, including cardiotoxicity, were shown. CEF seems to be feasible regimen as an adjuvant treatment for breast cancer.
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PMID:[The feasibility of CEF (cyclophosphamide, epirubicin, 5-FU) regimen in the adjuvant setting of primary breast cancer]. 912 4

There is evidence to suggest that single-agent broad spectrum antibacterials may be cost-effective alternatives to combination antibiotics for the empirical management of febrile neutropenia in cancer patients. The objectives of the present study were 2-fold. The first objective was to compare the clinical effectiveness of ceftazidime monotherapy with that of 2 combination antibiotic regimens in cancer patients with febrile neutropenia. The 2 comparator regimens consisted of tobramycin plus piperacillin, either with (regimen 'CAP') or without (regimen 'AP') cefazolin. The second objective was to perform a cost-effectiveness analysis of the 3 regimens. Meta-analysis of randomised comparative trials between the 3 therapy groups was performed to determine the average overall response rate after 3 to 5 days of treatment. Seven clinical studies were selected for analysis. The overall incidence of adverse drug reactions (ADRs) was determined using the results of comparative and noncomparative studies. A comparative cost-analytic model was applied from a hospital perspective. The costs of primary therapy, hospitalisation, laboratory tests, routine patient care and treating ADRs were calculated, as were future costs. Monotherapy with ceftazidime was associated with an overall response rate of 63.5% and mean per-patient costs of $Can12,000 to $Can14,000. In comparison, regimen AP was associated with an overall response rate of 58.8% and mean costs of $Can13,000 to $Can16,000 per patient. The overall response rate in patients receiving CAP was 75.3%, and the mean cost per patient was $Can11,000 to $Can12,000. Thus, regimen CAP was the most cost-effective therapy from a hospital perspective.
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PMID:Pharmacoeconomic analysis of empirical therapy with ceftazidime alone or combination antibiotics for febrile neutropenia in cancer patients. 1015 93

Breast cancer remains a major cause of morbidity and early death in women worldwide. Despite the responsiveness of advanced breast cancer to a number of chemotherapeutic and hormonal agents, long term outcome remains poor. The introduction of paclitaxel with a novel mechanism of action has kindled a ray of hope. Combination of paclitaxel with anthracyclines are being tried, with varying degree of success. Twenty patients with metastatic or locally advanced breast cancer were treated with Paclitaxel (175 mg/m2) and Epirubicin (80 mg/m2) administered sequentially. Each patient received 3 to 6 such cycles at 3 weekly intervals. A response rate of 85% (95% Confidence Interval (CI) 69%-100%) was observed in these patients with 25% (95% CI 6%-44%) achieving complete response. A response rate of 100% was observed in the six patients with locally advanced disease who had not received any chemotherapy earlier. Grade III neutropenia occurred in 5 patients and was reversible in all the cases. This combination is well tolerated. Its efficacy is being compared in a randomised trial with CAF regime in advanced breast cancer in our center.
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PMID:Paclitaxel-epirubicin in advanced breast cancer. 1077 59

The patient was a 46-year-old women who was treated for axillary lymph node recurrence of breast cancer by a variety of methods, including surgery, chemotherapy, and radiotherapy, but who experienced recurrences in the cervical and mediastinal lymph nodes and skin, and developed hydrothorax and ascites. Although the recurrent foci responded to 4 cycles of CAF chemotherapy, there was concern that the foci would become refractory or resistant to chemotherapy. The administration of paclitaxel was therefore initiated. The patient received a dose of paclitaxel once a week for 5 consecutive weeks followed by a 1-week recovery period (one cycle). After two cycles of the paclitaxel treatment, a marked shrinkage of the lymph nodes and complete resolution of the hydrothorax and ascites were observed. Even though the patient exhibited bone marrow suppression and G-CSF was administered twice for neutropenia, there were no adverse effects except mild alopecia, again suggesting the possibility that paclitaxel is effective chemotherapy for recurrent breast cancer.
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PMID:[Recurrent breast cancer successfully treated with a weekly dose of paclitaxel--a case report]. 1120 84

In order to explore activity and pharmacokinetic data of a docetaxel-epirubicin combination we analyzed a population of 60 metastatic breast cancer patients. All the patients had an ECOG performance status < 3; 41 patients (68%) had visceral metastases as dominant site of disease, including 33% with liver metastases. Three or more involved organs were present in 43% of patients; 35% had received prior hormonotherapy; 10% for metastatic disease. Twenty-five patients (42%) had received prior adjuvant chemotherapy; 15% a CAF regimen. Twenty per cent of patients had less than 12 months disease-free interval. Docetaxel and epirubicin were both given at a dose of 75 mg/m2 i.v. d. 1 every 3 weeks. After a median of six cycles we had 5 CR (8.3%), 40 PR (66.6%), 7 NC (11.6%), and 8 PD (13.3%). Response rates in patients with visceral and liver metastases were 78% and 55% respectively. Premenopausal status, < 1 year disease free survival and > 3 metastatic sites were associated with a lower response rate. After a median follow-up of 19 months (12-36), median disease-free survival is 11 months and median overall survival has not been reached. Grade 4 neutropenia was observed in 75% of courses but with febrile neutropenia in 6.2% of courses only. Non-hematologic toxicity wasn't clinically important. A NYHA class III reversible cardiac failure was observed in one patient (1.6%). The pharmacokinetic evaluation in 16 patients has shown that docetaxel transiently interfered with epirubicin plasma level when docetaxel was administered 1 h after epirubicin.
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PMID:Clinical and pharmacokinetic data of a docetaxel-epirubicin combination in metastatic breast cancer. 1180 82


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