Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a case of alveolar rhabdomyosarcoma (AR) with massive infiltration of bone marrow at presentation, and initial diagnosis in bone marrow aspirate. A 35 year old man presented with a submandibular mass, and hematomas after mild traumatisms. Peripheral blood showed thrombocytopenia and a normocytic anaemia. Bone marrow film showed diffuse involvement by undifferentiated blasts with rhabdomyoblastic features. Subsequent biopsy of submandibular lymph node confirmed the diagnosis with positivity for specific muscle actin and desmin, and negativity for lymphoid markers. Initial presentation of AR with extensive bone marrow involvement is extremely rare, and it could lead to wrong diagnosis and treatment of acute leukaemia, with the serious consequences that this would have. Immunohistochemical study and morphologic differential features can be of great diagnostic help.
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PMID:[Alveolar rhabdomyosarcoma with massive infiltration of the bone marrow as its initial manifestation]. 974 Dec 33

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

Irinotecan [7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonyloxy-camptothec in] administered i.v. in two courses, each course consisting of administration every day for 5 days [(dx5)2] on days 1-5 and 8-12, has demonstrated significant activity against advanced human tumor xenografts derived from colon adenocarcinomas and several childhood cancers. To build on this therapy, we have evaluated the combination of irinotecan given on this schedule with 5-fluorouracil given on days 1, 7, and 14 with or without leucovorin [(dx5)3 i.v.] against colon tumors, or combined with etoposide administered (dx5)2 i.v. either 2 h before or 2 h after irinotecan for treatment of colon tumors and rhabdomyosarcomas. A combination of 5-fluorouracil at 75% and irinotecan at 50% of their respective maximum tolerated doses when administered as single agents on this schedule gave acceptable toxicity. Against colon adenocarcinoma xenografts, 5-fluorouracil did not enhance the response rate compared with that obtained with the optimum dose of irinotecan given as a single agent. Against GC3/TK- xenografts, which lack thymidine kinase and cannot salvage thymidine to circumvent the inhibition of thymidylate synthase, the addition of leucovorin to the combination increased the complete response rate from 10 to >90%, whereas the response rates for the optimal doses of irinotecan or 5-fluorouracil, as single agents, were 30 and <10%, respectively. Etoposide d x 5 i.v. for two or three courses or (d x 5)3 p.o. did not cause objective regression of any colon tumors. In contrast, three of five rhabdomyosarcoma lines demonstrated a high frequency of partial regressions or complete regressions when treated (d x 5)1 i.v. Repetitive courses [e.g., (d x 5)2 or (d x 5)3] i.v. or p.o. or by 4-h infusion d x3 i.v. were either equally effective or less effective. Irinotecan and etoposide were combined using the (d x 5)2 i.v. schedule for both drugs, in which irinotecan was given 2 h before or 2 h after the administration of etoposide. Each drug could be combined at only 38% of its respective maximum tolerated dose when administered as a single agent, indicating greater than additive toxicity. Toxicity was similar irrespective of the sequence of administration and was manifested by loss of weight (73% of the initial weight, nadir day 7), myelosuppression, and prolonged thrombocytopenia. The responses of colon carcinomas to the combination given in either sequence were similar to that achieved with irinotecan given alone at the same dose as used in the combination. Similarly, when etoposide was given before irinotecan, the responses of rhabdomyosarcomas were similar to those for irinotecan. However, in experiments in which etoposide was administered 2 h after each dose of irinotecan, there was significant antagonism of the antitumor activity of irinotecan.
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PMID:Evaluation of irinotecan in combination with 5-fluorouracil or etoposide in xenograft models of colon adenocarcinoma and rhabdomyosarcoma. 981 97

Carzelesin (U-80244), one of the synthetic DNA minor groove binding cyclopropylpyrroloindole analogues, was selected for clinical development because of its high potency, promising antitumor activity in murine solid tumors and leukemia, and significant therapeutic efficacy against colon and rhabdomyosarcoma xenografts. In this Phase I study, carzelesin was given daily for 5 consecutive days to (a) determine the maximum tolerable dose (MTD) and the pattern of toxicity of this schedule; (b) define the pharmacokinetic profile of the parent, as was done for the intermediate compound U-76073 and the DNA-reactive agent U-76074; and (c) document any antitumor activity observed. Carzelesin was given as a 10-min infusion with a constant-rate infusion pump. Treatment was repeated every 4 weeks or when blood counts had recovered to normal values. The starting dose of 12 microgram/m2/day was escalated by 20-30% increments until the MTD (defined as the dose leading to grade 4 hematological or grade 3 nonhematological toxicity in at least two of six patients) was reached. Pharmacokinetic studies were planned on days 1 and 5 of the first cycle in at least two patients per dose level. Plasma levels of carzelesin, U-76073, and U-76074 were determined by high-performance liquid chromatography with UV detection and a detection limit of 0.5 ng/ml. Twenty-five patients were entered in the study, and 56 cycles were evaluable for hematological toxicity. Subsequent dose levels evaluated were 24, 30, 35, and 40 microgram/m2. Both neutropenia and thrombocytopenia were dose limiting and cumulative, with a high interpatient variability. Neutropenia occurred earlier (median time to neutrophil nadir and recovery, 15 and 29 days, respectively) than thrombocytopenia (median time to platelet nadir and recovery, 25 and >/=26 days, respectively); there were delays of treatment because of persisting thrombocytopenia in all patients treated at the MTD. At the MTD, the peak plasma concentrations of carzelesin were achieved at the end of the infusion and were higher than those found cytotoxic in vitro against tumor cell lines. Carzelesin was detectable up to a maximum of 1 h after the infusion. Smaller amounts of U-76073 were detectable for a maximum of 30 min only at the MTD, whereas U-76074 was never found. An 8-month partial remission was reported in one previously untreated patient with hepatocellular carcinoma at 40 microgram/m2. The MTD was fixed at 40 microgram/m2 daily; 35 and 30 microgram/m2 are the daily doses recommended for Phase II studies in good- and poor-risk patients. The daily regimen for 5 days seems to offer no advantage over the single intermittent schedule that has been selected for the Phase II program in Europe.
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PMID:Phase I clinical and pharmacokinetic study of carzelesin (U-80244) given daily for five consecutive days. 981 22

Topotecan and vincristine were evaluated alone or in combination against 13 independent xenografts and 1 vincristine-resistant derivative, representing childhood neuroblastoma (n = 6), rhabdomyosarcoma (n = 5), or brain tumors (n = 3). Topotecan was given by i.v. bolus on a schedule found previously to be optimal. Drug was administered daily for 5 days on 2 consecutive weeks with cycles repeated every 21 days over a period of 8 weeks. Doses of topotecan ranged from 0.16 to 1.5 mg/kg to simulate clinically achievable topotecan lactone plasma systemic exposures. Vincristine was administered i.v. every 7 days at a fixed dose of 1 mg/kg. Given as a single agent, vincristine induced complete responses (CRs) in all mice bearing two rhabdomyosarcomas (Rh28 and Rh30) and some CRs in Rh12-bearing mice (57%) but relatively few CRs (<29%) in other tumors. As a single agent, topotecan induced CR in a low proportion of tumor lines. A dose-response model with a logit link function was used to investigate whether the combination of topotecan and vincristine resulted in greater than expected responses compared with the activity of the agents when administered alone. Only CR was used to evaluate tumor responses. The combination resulted in significantly greater than expected CRs than individual agents in nine tumor lines (four neuroblastoma, three brain tumors, and two rhabdomyosarcomas). Similar event-free (failure) distributions were shown in SJ-GBM2 glioblastoma xenografts, whether vincristine was administered on day 1 or day 5 of each topotecan course. To determine whether the increased antitumor activity with the combination was attributable to a change in drug disposition, extensive pharmacokinetic studies were performed. However, little or no interaction between these two agents was determined. Toxicity of the combination was marked by prolonged thrombocytopenia and decreased hemoglobin. However, approximately 75 and 80% of the maximum tolerated dose of each single agent, topotecan (1.5 mg/kg) or vincristine (1 mg/kg), could be given in combination, resulting in a combination toxicity index of approximately 1.5. These results show that the therapeutic effect of combining topotecan with vincristine was greater than additive in most tumor models of childhood solid tumors, and toxicity data suggest that this can be administered to mice with only moderate reduction in the dose levels for each agent.
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PMID:Synergy of topotecan in combination with vincristine for treatment of pediatric solid tumor xenografts. 1058 79

The purpose of this study was to determine the toxicity, maximum tolerated dose, and pharmacokinetics of a 21-day continuous infusion of topotecan in children with relapsed solid tumors. Fifteen patients received 40 courses of continuous ambulatory infusions of topotecan every 28 days or when there was resolution of hematological toxicity and any grade 2 or greater nonhematological toxicity. The starting dose was 0.4 mg/m2/day. Total topotecan levels were measured on days 1, 7, 14, and 21. Three of four patients who received a starting dose of 0.4 mg/m2/day experienced dose-limiting myelosuppression. At the reduced dose of 0.3 mg/ m2/day, only two of the seven patients experienced dose-limiting myelosuppression. Subsequently, four patients with more limited prior therapy were treated with 0.4 mg/m2/ day; three had dose-limiting myelosuppression. Two patients with a dose-limiting toxicity at 0.4 mg/m2/day tolerated additional courses at 0.3 mg/m2/day. An equal number of patients had grade 4 neutropenia or thrombocytopenia. Other adverse events were rare. Two patients with ependymoma, one with rhabdomyosarcoma, and one with retinoblastoma metastatic to the brain had objective responses. The steady state plasma concentration and clearance of topotecan (Css) was achieved by day 1. Css in six patients with complete data were 1.44 +/- 0.50 and 2.13 +/- 0.83 ng/ml at 0.3 and 0.4 mg/m2/day, respectively. Thus, a 21-day topotecan infusion was well-tolerated at 0.3 mg/m2/day. Myelo-suppression was the dose-limiting toxicity at 0.4 mg/m2/day. The steady state and clearance of topotecan in this study are similar to those reported in adult patients.
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PMID:Phase I study of topotecan administered as a 21-day continous infusion in children with recurrent solid tumors: a report from the Children's Cancer Group. 1063 25

The authors examined 8 patients with pretreated relapsing or resistant solid tumors (Wilms'--4, rhabdomyosarcoma--3, synovial sarcoma--1) who received 16 courses of chemotherapy: iphosphamide, 1800 mg/m2/day (days 1-5), vepeside, 100 mg/m2/day (days 1-5), and carboplatin 500 mg/m2/day (day 1) (IVC) and 18 courses of therapy wherein iphosphamide was replaced by cyclophosphanum, 400 mg/m2/day (days 1-5) (CVC). The patients received 2-4 induction courses (n = 18) and 1-5 consolidation courses (n = 16) with reinfusion of peripheral stem cells (PSC). All PSC separations were performed after the first or second courses of IVC/CVE. There were no significant increases in the duration of leukopenia and thrombocytopenia, in the incidence of infection with a higher ordinal of a course performed by PSC maintenance. The findings suggest that the small doses of PSC stimulated by colony-stimulating factor can maintain hemopoiesis and decrease the rate of the estimated bone marrow depletion long after repeated courses of chemotherapy in patients with prognostically poor solid tumors.
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PMID:[Use of subgrafting doses of peripheral stem cells is a new approach to overcoming hematological toxicity of multiple intensive courses of chemotherapy in children]. 1094 56

Actinomycin-D (Act-D) is a rare cause of veno-occlusive disease (VOD). Between 1993 and 1998, we managed 6 patients, all male, median age 19 months (range 6-48 months) who received Act-D for Wilms' tumour (n=4), clear cell sarcoma (n=1) or rhabdomyosarcoma (n=1). VOD presented with a median platelet count of 12 x 10(9)/l, INR 3.8, fibrinogen 16 mg/l, fibrinogen degradation products (FDPs) > or =80 microg/l, aspartate aminotransferase (AST) 6922 IU/l, bilirubin 47 micromol/l. In 3 cases, transient liver dysfunction and thrombocytopenia without neutropenia had been observed after a previous course of Act-D. All six children developed encephalopathy, hepatomegaly, ascites, reversed portal flow and renal impairment. All received mechanical ventilation and two required haemofiltration. The treatment was supportive. Severe Adult Respiratory Distress Syndrome developed in 3 patients, all of whom died. 3 patients recovered. The outcome of VOD with multi-organ failure is poor. Intravascular coagulopathy precedes and characterises severe VOD during Act-D treatment.
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PMID:Veno-occlusive disease with multi-organ involvement following actinomycin-D. 1137 45

The authors report a case of severe dactinomycin-induced thrombocytopenia in a child with alveolar rhabdomyosarcoma. The phenomenon is consistent with an immune process leading to the formation of platelet-specific antibodies. This study shows that this can be induced even with the first dose of actinomycin, and its persistence is unpredictably prolonged and does not correlate linearly in an inverted fashion with the platelet count. It will be important to identify the subsets of patients who can develop this phenomenon by molecular techniques and to define the exact mechanism in vitro leading to formation of these antibodies. This would facilitate profiling the therapy, preventing the need for multiple platelet transfusions with their obvious hazards.
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PMID:Immune-mediated thrombocytopenia following dactinomycin therapy in a child with alveolar rhabdomyosarcoma: the unresolved issues. 1554 19

Although it is recognized that aggressive soft tissue sarcomas may give rise to cardiac metastases, these manifestations are usually late and clinically silent, being the prevailing finding in exceptional cases. This report describes the occurrence of a massive cardiac metastasis at diagnosis of leg rhabdomyosarcoma in a middle-age adult. This manifestation was the cause of rapidly progressive congestive heart failure and, together with the unusual occurrence of autoimmune thrombocytopenia, led to difficult patient care with a significantly negative influence on the outcome.
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PMID:Unusual manifestations of disseminated neoplasia at presentation: right-sided heart failure due to a massive cardiac metastasis and autoimmune thrombocytopenia in pleomorphic rhabdomyosarcoma of the adult. 1646 13


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