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)

We undertook a phase II trial in 17 patients with malignant glioma and large measurable disease to assess response rate and survival with pre-irradiation chemotherapy, using higher doses than standard, trying to improve the outcome. Patients characteristics were: male/female 10/7, age 49 (range 23-59), median Karnofsky index 90% (range 70-100), glioblastoma multiforme/anaplastic astrocytoma 14/3. Treatment consisted of 2 cycles of carboplatin 200 mg/m(2) days 1-3 (or AUC x 8, total dose) plus cyclophosphamide 1000 mg/m(2) days 1-3. One partial response (6.5%) and two stabilizations (13.5%) were observed after pre-irradiation chemotherapy. Twelve out of 15 patients (80%) progressed after chemotherapy. Median survival time was 7.6 months and the survival at 1 year was 33%. Main toxicity was hematologic in the first cycle: neutropenia grade 4 in 100%; thrombocytopenia grade 4 in 73% and grade 3 in 27%; anemia grade 3 in 7%; in the second cycle: neutropenia and thrombocytopenia grade 4 in 100% and anemia grade 3 in 50%). No toxic death was related to treatment. This regimen showed limited activity in malignant glioma with large residual disease after surgery or biopsy.
 ...
PMID:Pre-irradiation semi-intensive chemotherapy with carboplatin and cyclophosphamide in malignant glioma: a phase II study. 1190 9

To improve the efficacy and tolerance of the 5-fluorouracil (5-FU)/cisplatin combination in metastatic esophageal cancer, we designed a new therapeutic schedule, the HLFP regimen. 42 patients with metastatic oesophageal adenocarcinoma (n=10) or squamous cell carcinoma (n=32) were prospectively enrolled in the study. All had bidimensionally measurable disease. The HLFP regimen consisted of twice-monthly oral administration of hydroxyurea 1 g/m(2) on days 0, 1 and 2; a 2-h infusion of leucovorin 200 mg/m(2) and a bolus of 5-FU 400 mg/m(2) followed by a 22-h infusion of 5-FU 600 mg/m(2) on days 1 and 2; and, every two cycles, 80 mg/m(2) cisplatin on day 3. Relief of dysphagia and other symptoms were monitored, together with body weight changes. Major objective responses were observed in 24 patients (57%, 95% Confidence Interval (CI): 42-72%), including four complete responses (10%). The median progression-free survival and overall survival times were 8 and 12.7 months, respectively. Weight gain was observed in 48% of patients, and dysphagia improved in 76%. Grade 3-4 toxicity occurred in 40% of patients, with grade 4 neutropenia in 12% and grade 3 thrombocytopenia, vomiting and diarrhoea in 7-9% of patients. There were no treatment-related deaths. These results suggest that the HLFP regimen is an active and well-tolerated chemotherapy for metastatic oesophageal carcinoma.
 ...
PMID:Optimisation of 5-fluorouracil (5-FU)/cisplatin combination chemotherapy with a new schedule of hydroxyurea, leucovorin, 5-FU and cisplatin (HLFP regimen) for metastatic oesophageal cancer. 1191 43

Irinotecan and raltitrexed are active against advanced colorectal cancer, act through different mechanisms, and have non-overlapping toxicity profiles. In vitro studies have shown a schedule-dependent synergism between both drugs. The aim of this multicenter study was to determine the maximum tolerated dose (MTD) of this combination. Patients with 5-fluorouracil-refractory, advanced colorectal cancer were eligible. Dose escalation consisted of irinotecan (250-350 mg/m(2) as a 60-min infusion) in combination with a fixed dose of raltitrexed (3 mg/m(2) as a 15-min infusion, 1 h after irinotecan). Courses were repeated every 21 days. Three to 6 patients were to be included at each dose level. Dose limiting (NCI-CTC grade 3-4) toxicities (DLT) were assessed during the first 2 cycles. Thirteen patients were recruited (4, 3 and 6 in levels I, II and III, respectively). Main toxicity was diarrhea and asthenia, whereas myelotoxicity was mild. At level III, 2/6 patients experienced DLT (grade 4 diarrhea and neutropenia). The MTD was not reached, but further dose escalation was not attempted. Among 12 patients with measurable disease, 2 partial responses were observed for an overall response rate of 17%. The combination of single-agent full doses of irinotecan (350 mg/m(2)) and raltitrexed (3 mg/m(2)) in a 3-weekly schedule is feasible, with mild toxicity and a promising clinical activity. Diarrhea is the DLT, but it is not more common or severe than that described with irinotecan alone.
 ...
PMID:Multicenter phase I study of irinotecan plus raltitrexed in patients with 5-fluorouracil-refractory advanced colorectal cancer. 1218 70

On the basis of the demonstrated single-agent activity of cisplatin in patients with advanced cervical cancer and the observation of in vitro synergism between this agent and decitabine, a new DNA hypomethylating agent, we designed a phase II trial in which the combined use of the two agents are used as first-line therapy in patients with recurrent and/or metastatic disease. Eligible patients were those with histopathologically proven diagnosis of squamous cell carcinoma of the cervix, which was not considered suitable for curative surgery and/or irradiation, having measurable disease, leukocyte counts more than or equal to 4,000/microl, thrombocyte counts more than or equal to 100,000/microl, serum creatinine more than or equal to 1.5 mg/dl, and normal liver function tests. Initial dose of cisplatin was 40 mg/m(2), whereas decitabine was 50 mg/m(2) for 3 consecutive days every 21 days. Because of toxicity, the dose of cisplatin was reduced to 30 mg/m(2). Twenty-five patients were included in the study; 24 of them were eligible for the evaluation of toxicity, whereas 21 of them were eligible for the evaluation of tumor responses. Nineteen (79.2%) patients had received prior radiotherapy. A total of 75 cycles of chemotherapy were administered to the patients, with a median of 3 cycles (range: 1-8) per patient. The most frequently observed side effect was neutropenia, which was National Cancer Institute- Common Toxicity Criteria grades III and IV in 68.0% of cases. One patient died of complications caused by drug-related neutropenic sepsis. The most common nonhematologic grades III and IV toxicities were nausea and vomiting, which occurred in 17.3% and 9.3% of the cycles, respectively. Of a total of 21 patients evaluable for tumor response, 8 (38.1%) achieved a partial response, whereas stable disease was documented in 5 cases (23.8%). Median progression-free interval (PFI) was 16 weeks, and median survival was 19 weeks (95% CI 7.9-31.2). Objective responses were more frequent in patients with metastatic lesions in nonirradiated sites. Cisplatin- decitabine combination was moderately active in patients with advanced squamous cell carcinoma of the cervix, mainly in patients presenting with metastatic disease at previously nonirradiated sites. However, this regimen produced significant hematologic toxicity. Further studies with this combination including a larger patient population, preferably with the concomitant administration of hematopoietic growth factors, are warranted.
 ...
PMID:Phase II trial of cisplatin plus decitabine, a new DNA hypomethylating agent, in patients with advanced squamous cell carcinoma of the cervix. 1239 92

Many patients with metastatic transitional-cell carcinoma (TCC) are not appropriate candidates for standard cisplatin-based combination, because of inadequate renal function, poor performance status (PS), and other comorbid medical conditions. We have evaluated the efficacy and toxicity of a combination of carboplatin and vinblastine (CV) as a palliative regimen in these patients. The medical records of patients with metastatic TCC, who had been treated with CV at the British Columbia Cancer Agency from 1995 until 1999, were retrospectively reviewed. Treatment consisted of carboplatin (area under the curve = 5) on day 1, and vinblastine (4 mg/m(2)) on days 1 and 8, repeated every 4 weeks. A total of 42 patients were included in this study, of whom 39 had measurable disease. Median age was 73 years. Fifty-two percent of patients had a PS (Eastern Cooperative Oncology Group) of 2 or 3. Node-only disease was present in 26% of patients, bone metastasis in 26%, and liver metastasis in 24%. A total of 119 cycles were administered. Grade IV granulocytopenia occurred in 26% of patients, grade III anemia in 12%, and there were 3 episodes of febrile neutropenia occurring in two patients. The major nonhematologic toxicity was grade III fatigue in 17% of patients. There were no grade IV nonhematologic toxicity or treatment-related deaths. The overall response rate was 33% (13 of 39). Five patients (13%) achieved a complete response and 8 patients (20%) a partial response. The median duration of response was 32 weeks and median overall survival for all patients was 26 weeks. The combination of carboplatin and vinblastine given in this schedule is a feasible, well-tolerated, and active alternative for patients with metastatic TCC unfit for standard chemotherapy.
 ...
PMID:Carboplatin and vinblastine for the treatment of metastatic transitional cell carcinoma of the urothelial tract. 1239 96

A phase II study was conducted to assess the activity and toxicity of irinotecan (CPT-11) and carboplatin (CBDCA) combination chemotherapy for advanced non-small-cell lung cancer (NSCLC). Eligibility included chemo-naive advanced NSCLC patients with measurable disease and a good performance status. CPT-11 of 50 mg/m(2) was administered as a 90-min intravenous infusion on days 1, 8, and 15. CBDCA dosed to an area under the concentration-time curve of 5 mgmin/ml, using Calvert's formula, was administered by 90-min infusion after the CPT-11 infusion on day 1. Treatment was repeated 28 days interval for at least two cycles. Haematopoietic growth factors were not routinely used. From December 1997 to January 1999, 36 patients were entered into the study. The overall response rate was 25.0% (95% confidence interval: 12.1-42.2%). The median survival time and the 1-year survival rate were 10.2 months and 42.2%, respectively. Major toxicity by Japan Clinical Oncology Group criteria was as follows: grade 3-4 neutropenia 76.5%; grade 3 anemia 26.5%; grade 3/4 thrombocytopenia 47.1%; grade 3 nausea/vomiting 36.1%; grade 3-4 diarrhoea 5.9%; grade 3 alopecia 5.9%; grade 3-4 skin rush 2.9%. Four patients developed febrile neutropenia and only one had serious diarrhea induced by CPT-11. Actual relative delivery dose of CPT-11 to the projected one on days 8 and 15 were 0.86 and 0.43, respectively. It seemed that CPT-11 and CBDCA was more toxic regimen than CPT-11 and CDDP in advanced NSCLC. The relatively disappointing response rate could be related with low dose intensity of CPT-11.
 ...
PMID:Phase II study of irinotecan and carboplatin for advanced non-small cell lung cancer. 1244 53

Combination chemotherapy with newer, more active drugs in patients with advanced and/or metastatic bladder cancer might show improved response rate and survival. Gemcitabine (GEM) and Epidoxorubicin (EPI) have demonstrated activity in this disease. In addition, experimental studies in vitro have shown that the two agents have additive-synergistic effects when used in combination. Our prior phase I dose-finding study in previously untreated patients with advanced or metastatic bladder cancer defined recommended doses for further trials of GEM 1000 mg/m2 and EPI 25 mg/m2 on days 1, 8 and 15 every 28 days. A phase II trial at this dose level was initiated in previously untreated patients to assess efficacy and toxicity. Eligible patients had measurable disease; Karnofsky performance status (PS) of > 40; no prior chemotherapy; and adequate bone marrow reserve, cardiac, hepatic and renal function. Thirty- one patients (22 males, 9 females) with median age of 64 (range 44-75) and median PS of 80 were accrued, and all were eligible. Twelve patients had T4N1-2 M0, 8 had lymph node only metastases, while 11 had visceral metastases (liver, bone, lung). A total of 181 cycles was administered (range 3-7 per patient). Major toxicities (WHO grade > or = 3) were: neutropenia in 5 patients, thrombocytopenia in 2 patients, and anemia in 2 patients. Three patients had febrile neutropenic episodes and only 3 patients required dose reduction. Grade 1-2 non-hematological toxicities included nausea/vomiting, stomatitis and alopecia. No cardiac toxicity was observed. Of the 30 response evaluable patients, 17 (57%) demonstrated a major response (3 complete and 14 partial) (95% CI: 39%-75%), 7 had stable disease (23%) and 6 progressed (20%). These preliminary results confirm the phase I observation that the combination of GEM--EPI is highly active in the treatment of advanced and metastatic bladder cancer with a favourable toxicity profile.
 ...
PMID:Gemcitabine plus Epi-doxorubicin as first-line chemotherapy for bladder cancer in advanced or metastatic stage: a phase II. 1253 29

The efficacy of vinorelbine given as a continuous infusion was evaluated in 47 patients with breast cancer who had received previous treatment with first-line, second-line, and third-line chemotherapy including taxanes and/or anthracyclines. For inclusion into the study, patients were required to have histology-proven bi-dimensionally measurable disease. The treatment schedule was a bolus injection of vinorelbine 8 mg/m(2) administered over 5-10 minutes on day 1 followed by vinorelbine 8 mg/m(2) continuous infusion on days 1-4, every 21 days for 6 cycles. On an intent-to-treat basis, a 2% complete response rate and a 17% partial response rate were observed. The median time to progression was 2.4 months (95% CI, 1.83-2.97). Median survival was 7.73 months (95% CI, 4.48-10.98; range, 0.33-55.0 months). Major toxicities included febrile neutropenia in 40 cycles (24%) affecting 24 patients (51%) and 1 toxic death. Other nonhematologic toxicities included stomatitis (13%) and asthenia (13%). We conclude that this treatment shows considerable therapeutic activity, albeit at considerable toxicity costs, even in patients who have had multiple lines of prior chemotherapy. However, the results do not indicate clear advantages compared to the conventional weekly scheme of administration.
 ...
PMID:Vinorelbine as a 96-hour continuous infusion in heavily pretreated patients with metastatic breast cancer: a cooperative study by the GEICAM group. 1263 84

A pilot study investigated topotecan (Hycamtin, GlaxoSmithKline, Philadelphia, PA), a topoisomerase I inhibitor, in treating uterine serous carcinoma, a typically unresponsive aggressive tumor. Fifteen patients were surgically staged, then treated with topotecan (1.5 mg/m2, Days 1-5 every 21 days) as first-line therapy (n = 12) or secondary to platinum failure (n = 3). Patients received topotecan through six courses, disease progression, or unacceptable toxicity. Grade 3/4 hematologic toxicity prompted dose adjustments. Thirteen patients exhibited no gross evidence of residual disease postoperatively. At topotecan initiation, one patient had 5-cm and one had < 1-cm residual disease. Seventy-eight courses (median, six) were administered; 12 (80%) patients completed the specified protocol. Common serious toxicities included grade 3 neutropenia (33%), anemia (13%), and thrombocytopenia (13%). Eight patients received erythropoietin and/or granulocyte colony-stimulating factor. Median follow-up for 14 evaluable patients was 26 months (range, 13-40). Of 11 evaluable first-line topotecan patients, nine were alive at follow-up; five were disease-free. Of three second-line topotecan patients, two died and one was alive with disease 31 months post-treatment. One patient with measurable disease achieved a complete and one a partial response as assessed by computed tomography scan. Median progression-free survival was 25 months; median survival has not been reached at 26 months. Although topotecan's antitumor activity cannot yet be quantified, disease-free interval and survival outcomes compare favorably with other therapies in uterine serous carcinoma. Further evaluation of topotecan in this population is warranted.
 ...
PMID:A pilot study of topotecan in the treatment of serous carcinoma of the uterus. 1265 27

Our objective was to identify a new active three-drug combination regimen consisting of paclitaxel (PTX), epirubicin (EPI) and cisplatin as first-line line chemotherapy for advanced ovarian carcinoma. A phase I study was carried out to evaluate the dose-limiting toxicity (DLT) and the maximally tolerated dose (MTD) of PXT and EPI in combination with a fixed dose of cisplatin every 4 weeks. Side-effects were recorded according to the NCI Common Toxicity Criteria. Patients were treated in cohorts of three with fixed-dose cisplatin 80 mg/m2 and EPI 80-->100 mg/m2 and PXT 100-->160 mg/m2 until DLT was reached. Once MTD was identified, a single-step phase II study was therefore carried out to test the clinical activity and panel of toxicity of such regimen. Objective responses were recorded according to the WHO criteria. Time to progression and overall survival (OS) were secondary endpoints. The DLT was myelosuppression and, in more detail, febrile neutropenia, which occurred at the fifth dose level (PTX 140 mg/m2, EPI 100 mg/m2 and cisplatin 80 mg/m2) in two out of three patients. Other side-effects were grade 3 mucositis in two out of three patients and grade 3 anemia in one case. The combination of cisplatin 80 mg/m2 plus EPI 80 mg/m2 and PCT 140 mg/m2 every 4 weeks was considered as the MTD. In the phase II study a complete response was observed in six patients (33%) and a partial response in nine cases (50%) for an overall response rate of 83% [95% confidence limits (CL) 59-96%]. Median time to progression of patients with measurable disease was 16.4 months. Median OS was not reached after a follow-up of 42 months. This study demonstrated that PTX and EPI can be safely administered in combination with cisplatin to fit patients with advanced epithelial ovarian carcinoma. The three-drug regimen of cisplatin 80 mg/m2, EPI 80 mg/m2 and PTX 140 mg/m2 every 4 weeks is very active, at least in terms of objective response rate. This level of activity overlaps with the 95% CL of the activity of cisplatin alone; however, it does encourage future trials of the combination.
 ...
PMID:Escalating doses of paclitaxel and epirubicin in combination with cisplatin in advanced ovarian epithelial carcinoma: a phase I-II study. 1278 42


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