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)

Early clinical trials in adults showed favourable results of ifosfamide (IF) in several tumours. In a previous study we used IF and vincristine (VCR) and observed 6 complete responses (CR) among 25 previously heavily treated children. Especially patients with rhabdomyosarcoma (RMS) responded well, with 4 partial responses (PR) and 2 CR among 6 patients. This and the fact that the combination of VCR, actinomycin D (ACD) and cyclophosphamide (CYT) still give good results in RMS patients led us to replace CYT with IF in this combination. This IVA protocol consists of IF 3000 mg/m2 i.v. in 1 h on days 1 and 2, VCR 1.5 mg/m2 by i.v. push on day 1, and ACD 900 micrograms/m2 by i.v. push on days 1 and 2. The course is repeated at 28-day intervals. VCR 1.5 mg/m2 is given on day 14. We used this protocol als induction therapy in 18 newly diagnosed RMS patients. The primary sites were: abdomen (4 patients), bladder and prostate (3), head and neck (9: orbita 5), extremity (1), chest wall (1). At diagnosis, 9 patients had stage I, 4 stage II and 5 stage IV disease. Except for one mixed mesodermal type, all were of the embryonal type. The patients age at diagnosis varied from 2 to 16 years. After three courses, in some patients surgery was performed if radical tumour extirpation seemed possible. The first evaluation took place after three courses. At this point one patient had no response, one had a reduction in tumour mass of less than 50% (partial response PR), 9 patients had greater than 50% tumour-reduction (good partial response [GPR]), and 7 were in complete remission (CR). In 2 of these 7 (CR) no tumour was found on histopathological examination of the specimen. In patients with GPR or CR therapy was continued for 6 months and then stopped. Thirteen patients have been disease-free for 1-20 months from the date of CR. Four patients relapsed 4, 6, 11 and 11 months after CR. There was one therapy-related death. Except for this patient no major toxicity was encountered. These results indicate that by replacing CYT with IF, remission induction can be improved with a major contribution to survival and to enhanced quality of life in these patients.
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PMID:The role of ifosfamide in paediatric soft tissue sarcomas. 381 16

Bioptical verification of complete clinical remission achieved with postoperative chemotherapy in 140 pediatric patients with nonradically resected stages I and II nonparameningeal malignant mesenchymal tumors was evaluated. Tumor histology was rhabdomyosarcoma in 92 and nonrhabdomyosarcoma in 48 patients. All were included in the International Society of Pediatric Oncology "1984 Malignant Mesenchymal Tumors Study." Treatment given after nonradical surgery and before the biopsy consisted of 3 to 6 IVA courses (ifosfamide, vincristine, actinomycin D). Complete clinical remission (no tumor at physical examination, X-rays, sonography, computed tomography, scintigraphy) was bioptically confirmed in 52 rhabdomyosarcoma and 23 nonrhabdomyosarcoma cases, whereas in all the remaining patients (39 rhabdomyosarcoma and 22 nonrhabdomyosarcoma) complete clinical remission was not bioptically verified. Forty-eight-month local relapse rates were 51% in bioptically confirmed and 48% in nonbiopsied rhabdomyosarcoma patients. In nonrhabdomyosarcoma cases, relapse rates were 25% and 14%, respectively. In 4 cases, bioptical specimens contained tumor cells. In spite of aggressive treatment, only 1 is actually in remission. The total 48-month relapse rate (biopsied and nonbiopsied) was significantly higher in rhabdomyosarcoma patients (50%) than in nonrhabdomyosarcoma patients (26%). The value of bioptical verification of complete clinical remission seems to be limited in our series, when known that relapse rate in bioptically confirmed complete remission cases remained high and the outcome in rare "positive biopsy patients" was poor.
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PMID:Value of postchemotherapy bioptical verification of complete clinical remission in previously incompletely resected (stage I and II pT3) malignant mesenchymal tumors in children: International Society of Pediatric Oncology 1984 Malignant Mesenchymal Tumors Study. 823 76

The second International Society of Paediatric Oncology (SIOP) study for rhabdomyosarcoma (MMT84) had several goals. The two principal aims were: (1) to improve the survival of children with rhabdomyosarcoma; and (2) to reduce the late effects from therapy by restricting the indications for surgery and/or radiotherapy after good response to initial chemotherapy. A further aim was to investigate the role of high-dose chemotherapy in young patients with parameningeal primary tumours. 186 previously untreated eligible patients entered the study. Patients with completely resected primary tumour received three courses of IVA (ifosfamide, vincristine and actinomycin D). Patients with incompletely resected tumour received six to 10 courses of IVA according to stage. Patients achieving complete remission with chemotherapy alone did not usually receive radiotherapy or undergo extensive surgery, but patients remaining in partial remission received local therapy with surgery and/or radiotherapy. Only patients over 5 years of age with parameningeal disease and patients over 12 years with tumours at any site were given systematic irradiation. Complete remission was achieved in 91% (170/186) of all patients. With a median follow-up of 8 years, the 5-year overall survival was 68% (+/- 3% standard error of the mean (SEM) and the 5-year event-free survival 53% (+/- 4% SEM). These results show an improvement over previous SIOP study (RMS75) in which survival was 52% and event-free survival was 47%. Among the 54 patients who exhibited isolated local relapse, 35% (19/54) survived in further remission longer than 2 years after retreatment, including local therapy (surgery +/- radiotherapy). Analysis of the overall burden of therapy received by all surviving children (including primary treatment and treatment for relapse if required) showed that 24% (28/116) were treated by limited surgery followed by three courses of IVA, 29% (34/116) were treated by chemotherapy alone (after initial biopsy) and 13% (15/116) received chemotherapy plus conservative local treatment (limited surgery or radiotherapy for residual disease). Only 34% (39/116) received intensive local therapy defined as radical wide field radiotherapy or radical surgery or both. Compared with the results obtained in the previous SIOP study, treatment in MMT84 was based on response to initial chemotherapy and, despite an overall reduction of the use of local therapy, significantly improved survival for patients with non-metastatic disease. This trial, also for the first time, provides evidence that retreatment after local relapse can achieve long-term second remissions.
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PMID:Treatment of non-metastatic rhabdomyosarcomas in childhood and adolescence. Results of the second study of the International Society of Paediatric Oncology: MMT84. 984 54

A congenital rhabdomyosarcoma presented as a partially necrotic mass on the left forearm on delivery at term. Ulceration and persistent bleeding were managed by primary curettage followed by local resection including partial excision of the muscles of the extensor compartment of the forearm. The defect was resurfaced with a split skin graft. The surgery was followed by chemotherapy according to the IVA regime. There was no recurrence at 2 years of age and the limb was fully functional. The presentation and management of rhabdomyosarcoma are discussed.
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PMID:Congenital rhabdomyosarcoma. 1062 99

Rhabdomyosarcoma is the most common sarcoma of childhood. Fortunately, the goal of cure is realistic for the majority of patients with localized tumors. However, management of these patients remains challenging. The fact that the tumor arises in a wide variety of primary sites, some of which are associated with specific patterns of local invasion, regional lymph node spread, and therapeutic response, requires physicians to be familiar with site-specific staging and treatment details. In addition, rhabdomyosarcoma requires multimodality therapy that can be associated with significant acute toxicities and long-term effects, particularly when administered to young children. These factors sometimes present a dilemma as to the best approach to optimize the chance of cure, minimize toxicity, and respect quality of life. The purpose of this review is to discuss 'optimal' management of this complicated tumor. Since the tumor is relatively rare, requires highly specialized care, and important management questions remain to be answered, optimal management of rhabdomyosarcoma includes enrollment in clinical trials whenever possible. Appropriate management begins with establishing the correct pathologic diagnosis, histologic subtype, primary site, extent of disease (International Society of Pediatric Oncology [SIOP]-TNM-Union Internationale Contre le Cancer stage or Intergroup Rhabdomyosarcoma Study Group [IRSG] stage), and extent of resection (IRSG group). Cooperative groups throughout North America and Europe have defined risk-adapted treatment based on these factors; this treatment requires a coordinated management plan that includes surgery, chemotherapy, and usually radiotherapy. The surgical approach for rhabdomyosarcoma is to excise the primary tumor whenever possible without causing major functional or cosmetic deficits. Wide excision is difficult in some primary sites and can be complicated by the fact that the tumor grows in a locally infiltrative manner so that complete resection is often neither possible nor medically indicated. Incompletely resected tumors are generally treated with radiotherapy. The cooperative groups reduce the dose of radiation based on the response of the tumor to chemotherapy and delayed primary resection to differing degrees. Response-adjusted radiation administration may reduce the long-term effects of radiotherapy, such as bone growth arrest, muscle atrophy, bladder dysfunction, and induction of second malignant neoplasms; however, it may also be associated with an increased risk of tumor recurrence. All patients with rhabdomyosarcoma require chemotherapy. A backbone of vincristine and dactinomycin with either cyclophosphamide (VAC) or ifosfamide (IVA) has been established. Risk-adapted treatment involves reducing or eliminating the alklyating agent for patients with the most favorable disease characteristics. Clinical trials are ongoing to improve outcomes for higher risk patients; newer agents, such as topotecan or irinotecan, in combination with VAC or use of agents in novel ways are being investigated. Acute and long-term toxicities associated with these chemotherapy regimens include myelosuppression, febrile neutropenia, hepatopathy, infertility, and second malignant neoplasms. A 5-year survival rate >70% has been achieved in recent trials for patients with localized rhabdomyosarcoma. However, the outcome for patients who present with metastatic disease remains poor. In the future, risk-adapted classification of rhabdomyosarcoma will likely be based on biologic features, such as the presence of chromosomal translocations or specific gene expression profiles. It is hoped that newer therapies directed at specific molecular genetic defects will benefit all patients with rhabdomyosarcoma.
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PMID:Optimal management strategies for rhabdomyosarcoma in children. 1805 9

Developing precision medicine is a major trend in clinical oncology. The main adverse effects of ifosfamide, actinomycin D and vincristine (IVA) treatment for rhabdomyosarcoma are haematological toxicities such as neutropenia or thrombocytopenia. The severity of these effects vary among patients but their dynamic profiles are similar. A non-empirical adjustment of the chemotherapy dose to avoid severe toxicities could help secure the treatment administration. Twenty-four patients with rhabdomyosarcoma treated with IVA chemotherapy courses were selected. Before and during each cycle, routine multiple blood cell counts were performed allowing for a dynamic study of the haematological toxicities. We developed a machine learning analysis using a gradient boosting regression technique to forecast the ifosfamide induced haematological toxicities as a function of neutrophils and platelets initial levels and the initial ifosfamide dose. To validate models' accuracy, predicted and observed neutrophils and platelets levels were compared. The model was able to reproduce the dynamic profiles of the haematological toxicities. Among all cycles, the mean absolute errors between predicted and observed neutrophils and platelets levels were 1.0 and 72.8 G/L, respectively. Adjusting a patient's ifosfamide dose based upon the predicted haematological toxicity levels at the end of a treatment cycle could enable tailored treatment.
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PMID:Machine Learning Approach to Forecast Chemotherapy-Induced Haematological Toxicities in Patients with Rhabdomyosarcoma. 3270 21