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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The study aimed to determine the activity and toxicity of taxol in the treatment of recurrent or metastatic soft tissue sarcomas or osteosarcomas. The major findings are that five patients had stable disease after two cycles of chemotherapy but two of these patients were subsequently removed from the study at their own request. The other three patients progressed after an additional two cycles of chemotherapy. Seven patients progressed during the first two cycles and were removed from the study. One patient completed only one cycle of therapy and was deemed inevaluable for study response. There were eight episodes of grade 3 or 4 neutropenia and two episodes of grade 3 thrombocytopenia. One patient experienced grade 3 neurological toxicity and one patient grade 3 mucositis. Two patients are currently alive with progressing disease and one patient is alive with no evidence of disease after undergoing surgery and radiotherapy. The principal conclusions are that Paclitaxel is ineffective in treating recurrent or metastatic soft tissue sarcoma and osteosarcoma. Treatment at this dose is quite myelosuppressive, but toxicity is generally manageable. Further study of this agent is not justified in this setting.
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PMID:A phase II trial of paclitaxel in the treatment of recurrent or metastatic soft tissue sarcomas or bone sarcomas. 941 3

The efficacy and safety of docetaxel in clinical trials in patients with a variety of malignancies are reviewed. The overall response rate for docetaxel as a first-line treatment for metastatic breast cancer is 59%. Docetaxel in combination with doxorubicin or vinorelbine has proved particularly effective in the first-line treatment of metastatic breast cancer. Docetaxel is also one of the most active single agents in the treatment of non-small-cell lung cancer (NSCLC), producing an overall response rate of 27% when used as a first-line agent. Docetaxel plus cisplatin was more effective against NSCLC than either drug used alone, yielding response rates of 33-48%. Docetaxel has shown activity against a variety of other tumors, including ovarian cancer (response rate in second-line therapy, 34%), head-and-neck cancer (response rate in first-line therapy, 35%), and soft-tissue sarcoma (response rate in first-line therapy, 32%). The main toxic effect is grade 3-4 neutropenia, which occurs in 57% of treatment cycles but is brief and manageable. The dosage of docetaxel should be reduced from 100 mg/m2 to 75 mg/m2 if patients have neutropenia lasting more than one week, febrile neutropenia, or impaired liver function. Other adverse effects include severe fluid retention and asthenia. Some adverse effects can be avoided by administering corticosteroid premedication. Docetaxel has shown efficacy against a wide range of cancers in clinical trials and has a manageable adverse-effect profile.
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PMID:Efficacy and safety of docetaxel in clinical trials. 943 29

We report a multicentre phase II study of orally administered prolonged schedule etoposide in children with refractory or relapsed malignancy. 83 children were entered into the study. The largest diagnostic groups were neuroblastoma (n = 20), rhabdomyosarcoma/soft tissue sarcoma (n = 16) and brain tumours (n = 16). Etoposide was administered twice daily at a dose of 50 mg/m2/day for 21 days using the intravenous preparation given orally. Disease reassessment was performed after the second course. Etoposide plasma concentrations were measured by HPLC, 2 and 6 h after administration of therapy on days 7 and 14 in 15 patients. 61 patients completed two courses and were evaluable for response. There was 1 complete response (CR), 5 partial responses (PR) 22 stable disease (SD) and 33 progressive disease (PD). Of the 6 with responses, 3 had a diagnosis of medulloblastoma/cerebral primitive neuroectodermal tumour. 24 of 26 patients with SD/PR/CR received further courses with excellent palliative effect. The main toxicity observed was myelosuppression, with 8% and 7% of evaluable courses complicated by grade III-IV neutropenia and thrombocytopenia, respectively. Severe infection (grade III-IV) was rare, complicating only 2/94 evaluable courses. Plasma etoposide median concentrations at 2 h after administration on day 7 of course 1 were 1.5 (range 0.6-2.4) micrograms/ml. Total course 1 area under the etoposide plasma concentration versus time curve (AUC) values were estimated using a limited sampling model. Grade > or = 2 leucopenia was only observed in patients with a day 72 h etoposide concentration of > 2 micrograms/ml or a course 1 AUC of > 35 mg/ml.min. It is concluded that given at a dose of 50 mg/m2/day in two doses for 21 day courses, oral etoposide is well tolerated in children. A correlation between drug concentrations and toxicity was observed. Overall, a low response rate was seen (approximately 10%), but disease stabilisation appears to occur, and useful palliative effect was frequently noted. The response in brain tumours was more encouraging (3/14 PR) and this group requires further evaluation.
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PMID:Phase II study of 21 day schedule oral etoposide in children. New Agents Group of the United Kingdom Children's Cancer Study Group (UKCCSG). 947 Aug 39

The authors evaluated the novel chemotherapeutic regimen of paclitaxel (Taxol, Bristol-Myers Squibb, Princeton, NJ, U.S.A.) plus doxorubicin plus filgrastim--a granulocyte colony-stimulating factor (G-CSF)--in advanced or metastatic sarcoma. Eligible patients must have had histologically confirmed advanced previously untreated soft-tissue sarcoma. All patients must have had bidimensionally measurable metastases. Treatment consisted of doxorubicin, 50 mg/m2 by intravenous push, followed 4 hours later by paclitaxel, 150 mg/m2 by continuous infusion over 24 hours every 3 weeks, plus G-CSF, 5 microg/kg, on days 3 through 12 of each cycle. Cycles were repeated every 21 days. A one-time dose escalation for doxorubicin only (60 mg/m2) was allowed in all patients who experienced no significant toxicity after their first cycle of paclitaxel plus doxorubicin. From November 1993 through May 1996, 29 patients were entered in this study. Grade 3 anemia occurred in three patients. Grade 3--4 neutropenia occurred in 20 patients. Seven patients experienced at least one episode of neutropenic fever, including one death. Grade 3 thrombocytopenia occurred in four patients. There were six partial responses in 27 eligible patients, for a response rate of 22.2% (95% confidence interval, 7%-38%). Median time to progression was 4.5 months, and median overall survival was 10.2 months. The regimen of paclitaxel plus doxorubicin plus filgrastim as used in this study appears to have no more activity than single-agent doxorubicin.
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PMID:Paclitaxel (Taxol) plus doxorubicin plus filgrastim in advanced sarcoma: a phase II study. 962 89

The aim of this phase II trial was to examine the efficacy of a new nitrosourea, cystemustine, in soft tissue sarcoma. Between January 1990 and March 1991, 32 pretreated patients with advanced soft tissue sarcoma were enrolled. Cystemustine was given every 2 weeks at 60 mg/m2 via a 15-min i.v. infusion. All eligible patients were considered evaluable for response and toxicity (WHO criteria). Of the 32 enrolled patients, 4 were ineligible, leaving 28 evaluable patients. All but 1 had been pretreated: 6 with adjuvant chemotherapy, 18 patients with first-line palliative chemotherapy without nitrosourea, 3 with both treatments, and 18 had received radiotherapy. Median age was 54 years (range 20-73) and median performance status was 1 (0-2). One partial response (PR, duration 12 weeks), 2 stable disease and 25 progressions were observed, giving an overall response rate of 3.57% (confidence interval: 0.1-18.4%). Toxicity was mild, and was mainly neutropenia (no grade 3 or 4), thrombocytopenia (3.57% grade 3 and grade 4) and nausea-vomiting (no grade 3 or 4). It should be noted that the treatment for the patient who obtained a PR was third line with no previous response. Cystemustine with this schedule appears to have a low clinical activity and toxicity in advanced soft tissue sarcoma.
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PMID:Results of a phase II trial with second-line cystemustine at 60 mg/m2 in advanced soft tissue sarcoma: a trial of the EORTC Early Clinical Studies Group. 964 Feb 34

From 1987 to 1995, 22 children with refractory solid tumors entered a phase II study of high-dose thiotepa (HDT) (900 mg/m2) followed by stem cell transplantation (SCT) in the Pediatrics Department of the Institut Gustave Roussy. Tumor types were rhabdomyosarcoma (eight), osteosarcoma (seven), neuroblastoma (three), Ewing's sarcoma (three) and Burkitt's lymphoma (one). Before HDT, all had been extensively treated with conventional chemotherapy, surgical resection of the primary tumor (13/22) and of metastases (6/22), and radiotherapy of the primary tumor in three patients. All had measurable disease, at the site of the primary tumor (3 patients), of the metastases (9 patients) or both (10 patients). Toxicity from the HDT was severe but acceptable. No toxicity-related death occurred. The median duration of neutropenia and thrombocytopenia was 18 days (5-37) and 30 days (7-377), respectively. Septicemia was documented in four patients. Severe diarrhea was observed in seven patients. Mild hepatic toxicity occurred 18 times. No CR and 11/22 PR were documented: osteosarcoma 4/7, rhabdomyosarcoma 4/8, Ewing's sarcoma 2/3; 1/1 Burkitt's lymphoma progressed. We conclude that at a dose of 900 mg/m2 followed by SCT support in these heavily pretreated children, the main toxicity induced by thiotepa was digestive. The response rate observed, especially in sarcoma, is particularly encouraging. Thiotepa should be further evaluated in HDC regimens either in combination with other alkylating agents or in rapidly cycled courses of HDC with SCT.
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PMID:Phase II study of high-dose thiotepa and hematopoietic stem cell transplantation in children with solid tumors. 975 39

The response rate (RR) to single-agent chemotherapy with doxorubicin or ifosfamide in patients with advanced soft-tissue sarcoma (STS) is in the range of 20%. Paclitaxel is clinically useful in treating several solid tumors and has demonstrated activity in a series of human sarcoma cell lines. Twenty-eight patients with measurable advanced STS participated in this phase II trial of paclitaxel at 250 mg/m2 administered as a 3-hr i.v. infusion once every 3 weeks. All patients received granulocyte colony-stimulating factor (G-CSF) beginning on the day after paclitaxel and lasting until recovery from neutropenia. No prior chemotherapy had been used in 17 patients; 10 patients had had prior doxorubicin-based therapy; and 1 patient had had intraperitoneal therapy with edatrexate. Two partial responses (PRs) (7%; 95% confidence interval [CI] = 1-23%) were observed. The responding patients included a patient with angiosarcoma of the scalp who had complete regression of cutaneous lesions and improvement of nonmeasurable pulmonary disease lasting 6 months. The other PR occurred in a woman with metastatic uterine leiomyosarcoma and lasted 9 months. Seven patients had stable disease for 3-4 months. Median time to progression for all patients was 3.5 months (range: 2.5-9 months). The mean nadir in the white-blood-cell (WBC) count was 3.8 x 10(3)/microliter (range: [0.2-16.2] x 10(3)/microliter), with a mean nadir in the absolute neutrophil count (ANC) of 2.4 x 10(3)/microliter (range: [0.0-7.1] x 10(3)/microliter). Three patients died while in the study. Two patients with angiosarcoma of the scalp who did not qualify for this study were treated with paclitaxel off protocol, and experienced dramatic tumor regression. The overall response to paclitaxel observed in this heterogeneous group of patients was disappointing. However, the activity seen in angiosarcoma of the scalp suggests that further evaluation is warranted in patients with STS.
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PMID:Phase II trial of paclitaxel in patients with soft-tissue sarcoma. 977 50

Over 50% of patients with newly diagnosed rhabdomyosarcoma (RMS) are in the 'intermediate risk' group with a 3-year progression-free survival of approximately 65%. This group consists of stage 1, group III, non-orbit tumours; stage 2, group II and III; and all stage 3 patients utilising the Intergroup Rhabdomyosarcoma Study (IRS) staging system. The role of doxorubicin in the treatment of RMS has been controversial. Ifosfamide, both alone and in combination with etoposide, has significant activity in patients with RMS. The aim of this pilot study was to examine the efficacy and toxicity of a chemotherapy regimen of alternating cycles of vincristine/doxorubicin/cyclophosphamide and etoposide/ifosfamide for intermediate risk RMS. 30 patients with intermediate risk RMS or undifferentiated sarcoma (US) were treated with alternating cycles of vincristine/doxorubicin/cyclophosphamide (VDC) and etoposide/ifosfamide (EI) at planned intervals of 3 weeks. Local treatment of the tumour in most cases was performed after four cycles of chemotherapy, followed by an additional 10 cycles of chemotherapy. At a median follow-up of 37.5 months, the Kaplan-Meier estimate of 3-year event-free survival was 85% (95% confidence interval 72-99%). The overall survival at 3 years was 91% (95% confidence interval 80-100%). No patient died from toxicity. The most common toxicity was febrile neutropenia in 35% of VDC and 26% of EI cycles. No nephrotoxicity or cardiac toxicity was seen. No patient progressed prior to week 12 local therapy. Alternating cycles of VDC and EI are an effective treatment for patients with intermediate risk RMS and US. Toxicity is tolerable. Delaying local treatment until week 12 does not compromise outcome.
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PMID:Treatment of intermediate risk rhabdomyosarcoma and undifferentiated sarcoma with alternating cycles of vincristine/doxorubicin/cyclophosphamide and etoposide/ifosfamide. 984 84

Because of the low number of active cytotoxic drugs and their limited activity, the evaluation of new anti-cancer agents for their activity in soft tissue sarcomas is a continuing need. The objectives of this prospective phase II trial of gemcitabine were to estimate the response rate and to define the toxicities of prolonged infusions of low-dose gemcitabine in patients with pretreated advanced soft tissue sarcomas. Patients were eligible if they had a histologic diagnosis of unresectable, recurrent or metastatic, progressive soft tissue sarcoma, and if they had been treated with at least one prior chemotherapy consisting of an anthracycline- and/or ifosfamide-containing regimen. Gemcitabine was administered as a 360 min infusion on days 1, 8 and 15 of a 28 day cycle. The initial dose of gemcitabine was 200 mg/m2 in all patients. Dose escalation to 250 mg/m2 was allowed in the case of stable disease and good tolerability of the drug. All 18 patients (median age 58 years) who enrolled were treated with gemcitabine, and all were assessable for toxicity, response and survival. Only two of these 18 patients had an objective response to a previous palliative chemotherapy. A median of 3 cycles (range 1-7) of gemcitabicin were administered. Two (11%) of the patients had a partial response lasting 5 and 6 months, respectively. Both of these patients had only lung metastases. Whereas one of these patients had a transient partial response to the foregoing chemotherapy (consisting of ifosfamide and doxorubicin), the other patient has been progressive on these drugs. One additional patient, progressive on ifosfamide and doxorubicin, had an objective response of greater than 50% confined to the lungs and stable local recurrence for 6 months. Six patients had stable disease for 3-6 months and nine patients had disease progression. The median survival was 8 months. Treatment generally was well tolerated with six patients having transient grade 3 non-hematologic toxicity, four having grade 3 neutropenia, and one having grade 4 neutropenia and thrombocytopenia. Gemcitabine, given as a prolonged infusion at a low dose level, has a favorable toxicity profile and displays antitumor activity in patients with intensively pretreated, advanced soft tissue sarcomas.
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PMID:Phase II trial of gemcitabine in patients with pretreated advanced soft tissue sarcomas. 1091 48

We have previously reported the superiority of the epirubicin 180 mg/m2-cisplatin combination over single drug epirubicin 180 mg/m2 for advanced soft tissue sarcoma both in terms of response (54% vs. 29%, p = 0.025) and survival (p = 0.001). The aim of the present study was to establish whether decreasing the dosage of epirubicin to 150 mg/m2 would result in the same activity but with less hematological toxicity. One hundred fifty-nine patients with advanced soft tissue sarcoma were randomized for either epirubicin 150 mg/m2-cisplatin 120 mg/m2 (group A) or epirubicin 180 mg/m2-cisplatin 120 mg/m2 (group B). The results were as follows: group A: 79 patients were evaluated. Overall response rate was 24/79 (30%) (95% CI 21-41%). Median survival was 11 months and probability of survival at 1 year was 0.46. Grade IV granulocytopenia was present in 111/274 cycles and febrile neutropenia in 22/274. Group B: 73 patients were evaluated. The overall response rate was 39/73 (53%), (95% CI 42-64%). Median survival was 14 months and probability of survival at 1 year was 0.58. Grade IV granulocytopenia was present in 136/295 cycles and febrile neutropenia in 30/295. The differences were as follows: for overall response rate p = 0.004; power (for p = 0.05) 85%; for survival p = 0.09; for grade IV granulocytopenia p = 0.3; and for febrile neutropenia p = 0.61. A survival advantage (p = 0.043) was evident for patients randomized to group B and with performance status 0 or 1 compared with similar patients from group A. A plateau-like formation on the probability level of 0.26 on the survival curve started from month 26 onwards. In conclusion, both regimens share the same toxicity but epirubicin 180 mg/m2-cisplatin seems more active in soft tissue sarcoma, possibly indicating a breakthrough for activity between an epirubicin dosage of 150 mg/m2 and 180 mg/m2 in combination with cisplatin. The superiority of the epirubicin 180 mg/m2-cisplatin regimen appears evident both in terms of response and survival.
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PMID:Epirubicin 150 mg/m2-cisplatin versus epirubicin 180 mg/m2-cisplatin for advanced soft tissue sarcoma. 1093 30


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