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

We conducted a prospective pilot study to assess the feasibility and safety of high-dose busulfan/melphalan as conditioning therapy prior to autologous PBPC transplantation in pediatric patients with high-risk solid tumors. From January 1995 to January 1999, 30 patients aged 2-21 years (median 8) were entered into the study. There were 14 females and 16 males. Diagnoses included neuroblastoma in 10 patients; Ewing's sarcoma and peripheral neuroectodermal tumor (PNET) in 15 patients and rhabdomyosarcoma in five patients. Treatment consisted of busulfan 16 mg/kg, orally over 4 days (from days -5 to -2) in 6 hourly divided doses, and melphalan at a dose of 140 mg/m2 given by intravenous infusion over 5 min on day -1. G-CSF mobilized PBPC were used as autologous stem-cell rescue. One patient developed a single generalized convulsion during busulfan therapy. The most relevant non-hematologic toxicity was gastrointestinal, manifesting as grade 2-3 mucositis and diarrhea in 12 patients. Two patients died of procedure-related complications, one from veno-occlusive disease of liver and multiorgan failure and the other from adult respiratory distress syndrome. Probability of treatment-related mortality was 6.6 +/- 4.5%. With a median follow-up of 18 months (range, 1-48), 19 patients are alive and disease-free, the actuarial EFS at 4 years being 55 +/- 12% for the whole group. We conclude that high-dose busulfan/melphalan for autologous transplantation in children with solid tumors is feasible even in small patients. It is well-tolerated, with an acceptable transplant-related mortality and has proven antitumor activity.
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PMID:High-dose busulfan/melphalan as conditioning for autologous PBPC transplantation in pediatric patients with solid tumors. 1064 2

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children younger then 15 years of age. The treatment of RMS localized in bladder or prostate still remains controversial. The aim of this study was analysis of treatment results in children with soft tissue sarcoma of bladder and prostate. From 1993 to 2001 the PPSTG has used three protocols to treat soft tissue sarcomas in children. The CWS-91 regimen has been served to treat stage I-III and SIOP-IV Intergroup study in stage IV. Since 1996 the CWS-96 protocol for all patients in stage I-IV has been used. After biopsy confirmation of the diagnosis patients were treated with chemotherapy and subsequent surgery. Radiotherapy was administrated with total dose 32Gy v 44.5Gy v 48Gy. The group of 19 patients aged from 3 months to 18 years with median age 6 y 4 m were evaluated. The median follow-up time was 42 months. RMS-embryonal was diagnosed in 11 patients, RMS-alveolare in 4 and others types in 4. Sixteen patients presented clinical stage III and 3 stage IV The tumours were primarily localised in bladder in 16 patients and prostate in 3. Eight were tumours of volume bigger than 10 cm. After induction chemotherapy two patients received partial cystectomy, 5 complete cystectomy and 3 complete cystectomy with genitourinary reconstructive. Eight patients did not receive surgery. The most common treatment failure was isolated, local relapse in 8 children particularly in patients with any second surgery. The EFS for all patients was 52% and for patients with localised RMS tumours 65%. Significant prognostic factors are the initial tumours volume, the lymph nodes infiltration and the response to the first chemotherapy cycle. Surgery is the most important procedure in local control of soft tissue sarcoma. Reconstructive options in poor and non responder patients can improve the EFS and life quality of those patients.
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PMID:[Soft tissue sarcoma of the bladder and prostate. A report of the Polish Paediatric Solid Tumour Group (PPSTG)]. 1595 4

Signaling through the type 1 insulin-like growth factor receptor (IGF-1R) occurs in many human cancers, including childhood sarcomas. As a consequence, targeting the IGF-1R has become a focus for cancer drug development. We examined the antitumor activity of CP-751,871, a human antibody that blocks IGF-1R ligand binding, alone and in combination with rapamycin against sarcoma cell lines in vitro and xenograft models in vivo. In Ewing sarcoma (EWS) cell lines, CP751,871 inhibited growth poorly (<50%), but prevented rapamycin-induced hyperphosphorylation of AKT(Ser473) and induced greater than additive apoptosis. Rapamycin treatment also increased secretion of IGF-1 resulting in phosphorylation of IGF-1R (Tyr1131) that was blocked by CP751,871. In vivo CP-751,871, rapamycin, or the combination were evaluated against EWS, osteosarcoma, and rhabdomyosarcoma xenografts. CP751871 induced significant growth inhibition [EFS(T/C) >2] in four models. Rapamycin induced significant growth inhibition [EFS(T/C) >2] in nine models. Although neither agent given alone caused tumor regressions, in combination, these agents had greater than additive activity against 5 of 13 xenografts and induced complete remissions in one model each of rhabdomyosarcoma and EWS, and in three of four osteosarcoma models. CP751,871 caused complete IGF-1R down-regulation, suppression of AKT phosphorylation, and dramatically suppressed tumor-derived vascular endothelial growth factor (VEGF) in some sarcoma xenografts. Rapamycin treatment did not markedly suppress VEGF in tumors and synergized only in tumor lines where VEGF was dramatically inhibited by CP751,871. These data suggest a model in which blockade of IGF-1R suppresses tumor-derived VEGF to a level where rapamycin can effectively suppress the response in vascular endothelial cells.
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PMID:The insulin-like growth factor-1 receptor-targeting antibody, CP-751,871, suppresses tumor-derived VEGF and synergizes with rapamycin in models of childhood sarcoma. 1978 39

The National Wilms Tumor Group (NWTS) presented the clinicopathological findings predicting relapse in children with stage III favorable-histology (FH) Wilms tumor (WT) treated in the NWTS-5 study. They reported that lymph node involvement and a microscopic residual tumor were highly predictive of the EFS and OS, and concluded that patients with different stage III criteria may receive different therapies. These data suggest that the current risk classification of WT is not satisfactory. Like other pediatric tumors, such as neuroblastoma and rhabdomyosarcoma, more systemic and detailed risk classification for WT should be established using various clinical and biological markers. In the previous therapeutic protocols for WT, no biological marker was used for risk classification. Therefore, it is important to identify effective biological markers related to the prognosis of WT. The presence of LOH at 1p and 16q was associated with a worse EFS and OS, and was used for risk classification to choose the treatment regimens used in the recent COG clinical trials. There are some candidate prognostic factors that can be used in the future risk classification of WT, such as the methylation status of RASSF1A. A worldwide cooperative study should be conducted in the future to confirm whether these factors are useful in the risk classification. The goal of treatment for WT is to identify approaches that provide excellent outcomes for children with low-risk tumors without the need for chemotherapy or XRT. Conversely, more aggressive therapy may be used for children with high-risk tumors in an effort to improve their survival. To meet these goals, a new effective risk classification for WT should be established via collaborative clinical trials.
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PMID:New risk classification is necessary in the treatment of Wilms tumor. 2683 22