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 combination Phase I study of gemcitabine hydrochloride with cisplatin was conducted in the patients with non-small cell lung cancer (NSCLC) at 5 investigation sites. Gemcitabine was administrated on day 1, 8 and 15 and cisplatin on day 1 of each 28-day cycle. The dosage of cisplatin was fixed to 80 mg/m2 and the dosage of Gemcitabine was gradually escalated in 3 dosing level from 600, 800 to 1,000 mg/m2. The maximum tolerated dose (MTD) and the recommended dose was determined with Continual Reassessment Method. For each dose level, 6 cases, 3 cases and 6 cases were registered respectively and all 15 cases were evaluable. In the dose level 3 with 1,000 mg/m2 of gemcitabine and 80 mg/m2 of cisplatin, grade 4 neutropenia was observed as DLT in 3 out of 6 cases, thus dose level 3 was considered as MTD and the recommended dose. Major adverse events were leukopenia, neutropenia, nausea/vomiting and anorexia. The incidence of such adverse events seemed to be dose-dependent and especially the grade of neutropenia seemed to be more serious as the dose increased. Also, the grade of liver function tests abnormal seemed to be more serious as the dose increased but the incidence as well as the grade did not have tendency of dose-dependent in another events including renal function tests abnormal. On the other hand, as to the efficacy PR was observed in 4 out of 15 cases. Based upon the results, it is necessary to discuss further the efficacy in the recommended dose in the combination therapy of gemcitabine and cisplatin.
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PMID:[Phase I study of gemcitabine hydrochloride (LY 188011) combination therapy with cisplatin in the patients with non-small cell lung cancer]. 1039 16

The purpose of this study was to determine the dose-limiting toxicities and the maximum-tolerated dose (MTD) of weekly administration of paclitaxel in patients with advanced solid tumors. Twenty-six patients with advanced solid tumors were treated with escalated doses of paclitaxel (starting dose 70 mg/m(2)/wk with increments of 10 mg/m(2)/wk) for 4 consecutive weeks every 6 weeks. No intrapatient escalation or growth factor support was allowed. The DLT was exceeded at the dose of 120 mg/m(2)/wk, and the dose-limiting events were grade IV neutropenia and treatment delay because of incomplete hematologic recovery. There was no cumulative myelosuppression. Grade IV neutropenia occurred in four (6%) cycles, and there was one episode of febrile neutropenia. Grade II/III fatigue occurred in 19 (73%) patients, resulting in discontinuation of treatment in 2 of them; grade II neurosensory toxicity and grade II alopecia occurred in 8 (31%) patients each. The MTD, which is also the recommended dose for further phase II studies, was 110 mg/m(2)/wk. Among the 21 patients with bidimensionally measurable disease, 2 (10%) partial responses were observed, both in patients with heavily pretreated advanced breast cancer. The weekly administration of paclitaxel for 4 consecutive weeks in cycles of 6 weeks is a feasible, safe, and active outpatient regimen that merits further evaluation in combination with other anticancer agents.
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PMID:A dose-finding study of the weekly administration of paclitaxel in patients with advanced solid tumors. 1147 74

We investigated efficacy and tolerance of chemotherapy with doxifluridine (5'-DFUR) and docetaxel (TXT) in advanced/recurrent breast cancer. Subjects were enrolled by central registration. The regimen included 5'-DFUR orally for 14 consecutive days, and TXT intravenously on day 8. It was repeated every 3 weeks, as long as possible, including dosage levels of 5 scheduled steps. Patient registration was started in August 1999 and 5 patients given level 1 regimen (5'-DFUR, 800 mg/day; TXT, 50 mg/m2) were evaluated. Although the results revealed neutropenia of grade 3 in 4/5 patients and leukocytopenia in 2/5 patients, no other side effects were observed. Taking into consideration the toxicity profiles of each drug in level 1, a level 2b regimen (5'-DFUR, 800 mg/day; TXT, 60 mg/m2) was accepted. Seven patients were registered for level 2b dosage and were examined for the safety of the regimen. Two patients discontinued the level 2b regimen due to percutaneous adverse reactions (DLT) and 6/7 patients developed neutropenia of grade 4. Clinical effects in level 1 group included: 1 CR, 2 PR, 1 long NC (NC longer than 24 weeks), and 1 NE, for a response rate of 60.0% (3/5 patients). Those in level 2b included: 2 CR, 2 PR, 1 NC, and 2 NE, for a response rate of 57.1% (4/7 patients). Based on the safety and efficacy of the combined therapy, the recommended dosage of this regimen is 5'-DFUR, 800 mg/day, combined with TXT, 60 mg/m2. A Phase II study is being conducted using this dosage.
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PMID:[A phase I study of docetaxel (TXT) and doxifluridine (5'-DFUR) combination therapy in patients with advanced and recurrent breast cancer]. 1147 46

Both weekly cisplatin chemotherapy and single agent topotecan have proven to be effective in recurrent ovarian cancer. Preclinical data show synergism between cisplatin and topotecan. Side effects for this combination are drug sequence dependent and predominantly haematologic. Since preclinical data suggest that Cremophor EL (CrEL), the formulation vehicle of paclitaxel, has a protective effect on haematological toxicity of cisplatin, CrEL was added to the combination cisplatin and topotecan. In this phase I study, escalating doses of oral topotecan administered on day 1, 2, 8, 9, 15, 16, 29, 30, 36, 37, 43, 44 were combined with weekly cisplatin 70 mg m(-2) d(-1) on day 1, 8, 15, 29, 36, 43 (scheme A) or with the presumably less myelotoxic sequence weekly cisplatin day 2, 9, 16, 30, 37, 44 (scheme B). In scheme C, CrEL 12 ml was administered prior to cisplatin in the sequence of Scheme A. 18 patients have received a total of 85 courses. In scheme A 4/10 patients, all treated with topotecan 0.45 mg m(-2) d(-1), experienced DLT: 1 patient had vomiting grade 4, 1 patient had grade 4 neutropenia >5 days, 1 patient had >2 weeks delay due to thrombocytopenia and 1 patient due to neutropenia. Both patients in scheme B (topotecan 0.45 mg m(-2) d(-1)) had DLT due to a delay > 2 weeks because of prolonged haematological toxicity. No DLT was observed in the first 3 patients in scheme C (topotecan 0.45 mg m(-2) d(-1)). However, 2 out of 3 patients treated at dose level topotecan 0.60 mg m(-2)d(-1) in scheme C experienced DLT due to >2 weeks delay because of persistent thrombocytopenia or neutropenia. We conclude that there is a modest clinical effect of CrEL on haematological toxicity for this cisplatin-based combination regimen, which seems to reduce these side effects but does not really enable an increase of the oral topotecan dose.
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PMID:Dose and schedule-finding study of oral topotecan and weekly cisplatin in patients with recurrent ovarian cancer. 1171 Aug 24

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.
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PMID:Multicenter phase I study of irinotecan plus raltitrexed in patients with 5-fluorouracil-refractory advanced colorectal cancer. 1218 70

We conducted a phase I study to evaluate the activity and tolerability of concurrent docetaxel and cisplatinum radiosensitization with hyperfractionated irradiation, in patients with advanced non-small cell lung cancer (NSCLC) and squamous cell carcinoma of the head and neck (SCCHN). Nine patients (5 stage III(A) and 4 III(B)) with NSCLC, and 15 with SCCHN (10 stage III and 5 IV) were treated with a b.i.d. hyperfractionated (HF) radiotherapy schedule. The normalized total dose for alpha/beta ratio = 10 Gy was 69.6 Gy for NSCLC and 80.5 Gy for SCCHN patients. The standard dose of cisplatin (10 mg/m(2)) was given combined to docetaxel on a weekly basis. The docetaxel starting dose level was 10 mg/m(2)/week and was escalated by 3 mg/m(2) increments in cohorts of 8 patients (5 SCCHN and 3 NSCLC). DLT (grade 3 malaise) was observed in 4 out of 8 patients treated at the 16 mg/m(2)/week docetaxel dose level. The 13 mg/m(2)/week docetaxel dose level was defined as the MTD causing grade 3 mucositis in 4 out of 8 patients. In total 4 (17%) patients developed grade 3 neutropenia. G-CSF support was given in 1/8, 4/8, and 5/8 patients treated at the 10, 13 and 16 mg/m(2) docetaxel dose levels respectively. Fatigue was the most common adverse event (5/24: 21%) and was responsible for more than 1 week treatment delay in 4 out of 8 patients treated at the 16 mg/m(2)/week docetaxel dose level. Nine (3 NSCLC and 6 SCCHN patients: 37.5%) had treatment delay of 1 week, while 7 (3 NSCLC and 4 SCCHN: 29%) had delays of 2 weeks for combined chemoradiation sequelae. Acute hypersensitivity reactions occurred in 3 (12.5%) patients, and grade 3 mucositis in 2/8, 5/8 and 6/8 patients, treated at 10, 13 and 16 mg/m(2)/week docetaxel dose levels respectively. The overall response rate was 79% (CI = 63-96%) with 33% and 53% CRs for NSCLC and SCCHN patients respectively. There were 3 deaths among 9 NSCLC and 4 among 15 SCCHN patients. Local and/or distant disease recurrences were shown in 4 NSCLC and in 6 SCCHN patients; 5 NSCLC and 9 SCCHN patients are alive with no evidence of tumor progression at 8.5 months mean follow-up time. Radiosensitization with docetaxel and cisplatin given concurrently with HF (b.i.d.) radiotherapy on a weekly basis is a promising approach and the recommended dose for further phase II studies is 10 mg/m(2)/week for both drugs. The antitumor activity shown was significant in both types of tumors. The incorporation of docetaxel in chemoradiotherapy regimens for future treatment of squamous cell carcinoma of the lung and head and neck, merits evaluation in phase II and III trials.
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PMID:A phase I trial of weekly docetaxel and cisplatinum combined to concurrent hyperfractionated radiotherapy for non-small cell lung cancer and squamous cell carcinoma of head and neck. 1246 68

In patients with non-resectable head and neck cancer concomitant chemoradiotherapy is increasingly used, especially in cases of oropharyngeal and hypopharyngeal tumours. Most chemoradiotherapy regimes contain cisplatin as a single agent or in combination with fluorouracil. However, not all patients are fit enough for a cisplatin-containing regime or they refuse hospital admission. Raltitrexed is a specific thymidylate synthase inhibitor that has been studied as a radiosensitiser in rectal cancer. Raltitrexed can be administered easily in an outpatient setting and has few short-term effects. We studied raltitrexed at escalating doses combined with standard radiotherapy in advanced head and neck cancer patients. Seventeen patients with locally advanced head and neck cancers were enrolled in the study. Raltitrexed was administered at dose levels of 1.5, 2.0, 2.5 and 3.0 mg/m(2) intravenously (i.v), once every 3 weeks, for two doses. Radiotherapy consisted of 70 Gy given over 7 weeks in five fractions of 2 Gy per week. In general, treatment toxicity (DLT), complicated febrile neutropenia, was observed at 3.0 mg/m(2) in two of four patients. The dose of 2.5 mg/m(2) was extended thereafter with additional patients without major toxicity. Radiotherapy had to be interrupted in one patient. Five patients had a clinical complete response(CR) and eleven a partial response (PR) six weeks after the last fraction of radiotherapy. Twelve out of 17 patients remained free of locoregional recurrence after a median follow-up of 24(+) months (range 3-60+ months). Raltitrexed, at a dose of 2.5 mg/m(2) given twice 3 weeks apart, can be administered in combination with 70 Gy of radiotherapy in locally advanced head and neck cancer patients with a manageable tolerability profile. The clinical results and convenience of the schedule make raltitrexed an attractive drug to explore further in patients considered unfit for cisplatin-containing chemoradiation regimens.
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PMID:Phase I study of concomitant chemoradiation with raltitrexed in locally advanced head and neck cancer. 1571 90

This is a phase I study to determine the maximum tolerated dose (MTD) and toxicity of a combination of TS-1 and weekly cisplatin (CDDP) in advanced gastric cancer patients. TS-1 was administered orally twice daily after meals, at a standard dose of 80 mg/m2. One course consisted of 21 days' consecutive administration followed by 14 days' rest. Cisplatin (CDDP) was injected intravenously on days 8, 15 and 22 using the following dose levels: dose level 1 20 mg/m2, dose level 2 25 mg/m2, and dose level 3 30 mg/m2. Twelve patients were entered in this trial. One of the 6 patients at dose level 3 had neutropenia NCI-CTC grade 3, while another patient at dose level 3 suffered from DLT (liver function grade 3. The maximal tolerable dose (MTD) was not reached using dose level 3. Partial responses were seen in 5 (62.5%) of 8 patients with evaluable lesions. At level 2 (25 mg/m2), the response rate was 100%. We recommended dose level 2 for phase II trials from the standpoint of toxicity and response rate.
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PMID:[A phase I study of TS-1 and weekly cisplatin in patients with advanced gastric cancer]. 1591 63

A phase-I clinical study of a combination therapy of vinorelbine and capecitabine was conducted in anthracycline- and taxane-pretreated patients with advanced/recurrent breast cancer. The objectives of this study in four medical institutions were to evaluate DLT (Dose Limiting Toxicity) and safety as primary endpoints, and tumor response and pharmacokinetics of vinorelbine as secondary endpoints. One 3-week course of treatment consisted of intravenous vinorelbine on Days 1 and 8 and oral capecitabine on Days 1 to 14, followed by a one-week rest. Vinorelbine was given at 20 mg/m(2) (Level 1) and 25 mg/m(2) (Level 2), and capecitabine was given at 1,650 mg/m(2)/day (in two divided doses, Levels 1 - 2). As the administration at each dose level in 3 patients did not cause DLT, 6 patients were additionally treated with vinorelbine at 25 mg/m(2) and capecitabine at 1,650 mg/m(2)/day (in two divided doses) to confirm safety. The major toxicities were bone marrow depression and gastrointestinal symptoms. In particular, the incidences of grade 3 or greater neutropenia (11 patients) and leukemia (10 patients) were high. They were reversible, however, and not severe enough to discontinue treatment. The response rate was 25.0% (3 PR/12). The combination with capecitabine did not affect the plasma pharmacokinetics of vinorelbine.
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PMID:[A phase-I clinical study of a combination therapy of vinorelbine and capecitabine in patients with advanced/recurrent breast cancer]. 1691 27

In a phase I study, we determined the maximum tolerated dose (MTD) and the recommended dose (RD) of nedaplatin (CDGP) in combination chemotherapy with Docetaxel (DOC) and 5-fluorouracil (5-FU) for treatment of carcinoma of the head and neck. Then, in a phase II study, we examined the efficacy and safety of the RD of chemotherapy. Fresh patients with squamous cell carcinoma of the head and neck were enrolled in the study. The dosage of chemotherapy was as follows: DOC 60 mg/m(2) on day 1 by infusion over 2 hours; CDGP 20-30 mg/m(2)/day on day 1 to 5 by infusion over 1 hour, and 5-FU 600 mg/m(2)/day on day 1 to 5 by 5 days continuous infusion. For CDGP, an initial dose level was set at 20 mg/m(2), and 3 patients were enrolled for each level of dose escalation. The DLT was defined here as grade 4 neutropenia or grade> or =3 non-hematotoxic reactions. The dose at which DLT was observed in overall 33% cases was taken as MTD. The RD for phase II study was estimated to be DOC 60 mg/m(2), CDGP 20 mg/m(2)/day, 5-FU 600 mg/m(2)/day. Forty patients were enrolled in the phase II study. DLT of neutropenia was noted in 2 of 38 cases. DLT of non-hematotoxic reactions was found in less than 33% of the cases; 17 cases showed CR, and 12 cases showed PR. The response rate was 76.3%. The overall response rate in histological assessment was 55.3%. The combination chemotherapy with Low-Divided Dose of CDGP, DOC and 5-FU was suggested to be safe and effective.
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PMID:[Phase I/II clinical trial of induction chemotherapy with nedaplatin (CDGP), docetaxel (DOC) and 5-fluorouracil (5-FU) for squamous cell carcinoma of head and neck]. 1722 Jun 68


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