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)

VP-16-213, a semisynthetic podophyliotoxin, was tested for antitumor and clinical toxicity in 126 children. The drug was administered iv daily x 5 days every 2 weeks at a starting dose of 75 mg/m2/day. The dose was increased by 25 mg/m2/day/course until clinical response or significant toxicity occurred. The only major toxicity was hematologic, with neutropenia as the most predominant feature. There was one local allergic reaction at the site of injection. No systemic allergic responses were reported. The drug demonstrated significant activity in acute myelomonocytic leukemia with four responses among 19 patients, less activity in acute myelocytic leukemia with two responses among 44 patients, and little activity in acute lymphocytic leukemia with only one partial response among 12 patients. Objective partial responses occurred in ten of 48 patients with solid tumors: two each with Wilms' tumor, lymphoma, and histiocytosis X, and one each with rhabdomyosarcoma, neuroblastoma, Ewing's sarcoma, and undifferentiated carcinoma. The inclusion of VP-16-213 in combination chemotherapy for childhood acute myelomonocytic leukemia and acute myelocytic leukemia appears indicated in patients relapsing after initial therapy. For solid tumors this is an interim report, with further patient accrual required before specific comments can be made.
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PMID:Phase II study of VP-16-213 in childhood malignant disease: a Children's Cancer Study Group Report. 29 6

Investigations with the melphalan-resistant human rhabdomyosarcoma xenograft TE-671 MR were carried out to identify patterns of cross-resistance and collateral sensitivity and to define the mechanism(s) mediating melphalan resistance. TE-671 MR was cross-resistant to thio-TEPA, mitomycin, vincristine, and cisplatin, and partially resistant to chlorambucil and cyclophosphamide. TE-671 MR and the parent line TE-671 were both resistant to 1,3-bis(2-chloroethyl)-nitrosourea and expressed similar levels of O6-alkylguanine-DNA alkyltransferase. TE-671 MR retained full sensitivity to actinomycin D and demonstrated enhanced sensitivity to VP-16 compared to TE-671. Treatment of TE-671 MR with melphalan plus VP-16 resulted in greater than additive growth delays. The frequency of hypoxic regions was similar in TE-671 MR and TE-671, respectively. Measurement of tumor-to-plasma levels at 180 min following i.p. administration of melphalan at 0.5 of the 10% lethal dosage showed mean tumor-to-plasma ratios of 3.81 in TE-671 MR and 7.38 in TE-671, respectively. The lower drug levels in TE-671 MR may be contributing to the resistance to melphalan and thus indicate the need for further studies to define the reasons for these differences in tumor drug level.
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PMID:Therapeutic analysis of melphalan-resistant human rhabdomyosarcoma xenograft TE-671 MR. 185 7

Based on previous work demonstrating the activity of cyclophosphamide and melphalan in a series of human medulloblastoma and rhabdomyosarcoma cell lines and transplantable xenografts, investigations were conducted to define the effects of combining cyclophosphamide or melphalan with VP-16. These studies demonstrated a synergistic interaction between cyclophosphamide and VP-16 and melphalan and VP-16 in the treatment of the human rhabdomyosarcoma cell line TE-671 growing in athymic mice. The combination of cyclophosphamide or melphalan with VP-16 may warrant consideration as a therapeutic strategy for solid tumors sensitive to bifunctional alkylating agents.
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PMID:Synergistic interactions between cyclophosphamide or melphalan and VP-16 in a human rhabdomyosarcoma xenograft. 229 68

A phase-II study of ifosfamide with mesna, given intravenously daily for five days by bolus injection, has demonstrated the activity of ifosfamide against a spectrum of childhood malignant solid tumors. Ifosfamide presently is being investigated in alternative phase-I schedules, daily times three or every other day times three with the aim of delivering comparable amounts of ifosfamide without increasing toxicity--specifically, neurotoxicity. Additionally, response following ifosfamide treatment is being evaluated for previously untreated children with osteosarcoma and rhabdomyosarcoma after 6 weeks of treatment, and for previously untreated patients with Ewing's sarcoma after 9 weeks of treatment with ifosfamide/VP-16 (etoposide) given in combination.
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PMID:Clinical studies of ifosfamide/mesna at St Jude Children's Research Hospital, 1983-1988. 249 67

A case of paratesticular rhabdomyosarcoma is presented. An 18-year-old male was admitted with the complaint of giant scrotal swelling and abdominal fullness on September 5, 1986. Left radical orchiectomy was performed with the pathologic diagnosis of alveolar rhabdomyosarcoma. The tumor was paratesticular in location and had invaded a spermatic cord. Radiological examination showed a gross metastatic mass in retroperitoneal lymph nodes, supraclavicular lymph nodes and Douglas pouch. The patient received induction chemotherapy containing vincristine, actinomycin-D, cyclophosphamide, bleomycin, CDDP and VP-16. After 3 courses, he had no mass in Douglas pouch and supraclavicular lesion. He received retroperitoneal lymph node dissection for residual retroperitoneal mass, and postoperative radiotherapy was given. However, recurrent disease was developed in the paraaortic region with malignant ascites. He was treated with salvage chemotherapy, had without any significant effect. He died of liver dysfunction due to progressive mass in hepatic hilum. A review of the current approach of paratesticular rhabdomyosarcoma with the usefulness of combination chemotherapy is given.
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PMID:[A case of advanced paratesticular rhabdomyosarcoma]. 265 9

Since 1978, six boys with prostatic rhabdomyosarcoma have been treated at our institution. Three had localized disease and were managed by initial biopsy, vincristine, actinomycin-D, and cyclophosphamide (VAC) chemotherapy, and bladder-sparing surgery with or without irradiation. Further combination chemotherapy ("pulse" VAC, Adriamycin, VP-16, cisplatin, and ifosfamide) was continued for 20 to 22 months following the induction course. Two boys had microscopic residual disease undetected by frozen section and unresponsive to radiotherapy. Subsequent total cystectomy 4 and 7 months later resulted in eradication of disease. In one patient, preservation of the bladder was achieved at the age of 3 months for 8 years. Artificial sphincter inserted to cure his urinary incontinence failed because of ischemia secondary to cuff compression and scar tissue. He is alive today with a modified Koch pouch urinary diversion. Of the 50% who had metastatic disease at presentation, two were dead within 12 months despite aggressive chemotherapy and irradiation. The third is currently on treatment. Although chemotherapy has markedly improved the prognosis, surgery is still necessary in most cases for cure. Bladder salvage is a desirable goal; however, residual microscopic disease, difficulty with frozen-section disease detection, and poor tissue vascularization for subsequent sphincter replacement remain significant obstacles.
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PMID:Rhabdomyosarcoma of the prostate in childhood: current challenges. 280 70

A phase II study of VP-16, a semisynthetic Podophyllotoxin, was performed in patients with solid tumors. VP-16 was administered orally at a dose of 200mg/day for 5 consecutive days at 3 to 4-week intervals. Out of 41 patients who were entered into the study, 35 patients comprising 17 lung cancer, 10 hepatoma and 8 other tumors were evaluable. There were 4 partial responses (23.5%) for lung cancer, 1 (10.0%) for hepatoma and 1 for rhabdomyosarcoma. Overall response rate was 18.2% for patients with prior chemotherapy and 15.4% for those given no prior chemotherapy respectively. Thus the results indicated VP-16 has no cross-resistance to other antitumor agents. Leukopenia (less than 4,000/mm3) and thrombocytopenia (less than 10 X 10(4)/mm3) were observed in 72.7% and 29.4% of the patients, respectively. Other toxicities were alopecia (59.5%) and gastrointestinal disturbances such as nausea (46.2%), vomiting (20.5%) and anorexia (20.5%), but these were all well tolerated.
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PMID:[Phase II study of VP-16 (capsule) in solid tumors. A cooperative study]. 298 32

Etoposide (VP-16), 150 mg/M2, given intravenously daily for 3 days every 3 weeks resulted in 3 complete responses and 6 partial responses in 154 patients with a spectrum of recurrent malignant solid tumors. There was evidence of disease control in an additional 37 patients (27 mixed responses and 10 stable disease). These responses occurred primarily in patients with Ewing's sarcoma, Hodgkin's disease, neuroblastoma and rhabdomyosarcoma. Most of the patients had every extensive prior therapy; however prior therapy with teniposide (VM-26), the congener of VP-16, did not seem to preclude responses to the latter drug. Myelosuppression was the principal form of toxicity. Neutropenia characterized by absolute neutrophil counts of 0.5 to 0.9 x 10(9)/L occurred in one-half of the patients, and thrombopenia with platelet counts of less than 25 to 49 x 10(9)/L in one-fourth. These results demonstrate a favorable therapeutic index for VP-16 in several recurrent childhood solid tumors, supporting its use as a component of primary therapy for these diseases.
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PMID:Clinical trial of etoposide (VP-16) in children with recurrent malignant solid tumors. A phase II study from the Pediatric Oncology Group. 341 Jun 65

We report a case of rhabdomyosarcoma of the prostate. The patient was a 56-year-old man who complained of anal pain and dysuria. Tumor of the prostate was suspected after rectal examination. Multiple metastatic lesions were found in the lungs and liver. A needle biopsy of the prostate revealed rhabdomyosarcoma. He received chemotherapy, using Etoposide and responded slightly. Subsequently VAC-therapy was also performed. Although the patient improved temporarily, he died 4 months after admission.
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PMID:[Rhabdomyosarcoma of the prostate]. 375 81

Sarcomas of childhood rank fifth in incidence of malignant tumors in children younger than 15 years. Among the soft tissue sarcomas, approximately 50% are rhabdomyosarcomas. The remainder represent a heterogeneous group of diverse sarcomas which are not unique to children and include fibrosarcoma, synoviosarcoma, malignant fibrous histiocytoma, malignant schwannoma, angiosarcoma, leiomyosarcoma, and others. The most common bone cancers in childhood are osteosarcoma and Ewing's sarcoma. Although a multidisciplinary approach utilizing surgery, irradiation, and combination chemotherapy is routinely used in management of virtually all children with solid tumors, the value of adjuvant chemotherapy in select bone and rare soft tissue sarcomas is currently being tested. Multiagent chemotherapy including vincristine, dactinomycin, cyclophosphamide, and Adriamycin (doxorubicin) contribute to cure rates in 65% to 75% of children with localized rhabdomyosarcoma, Stages I to III, when combined with surgery and/or irradiation. Other drugs which hold promise include platinum, DTIC, methotrexate, and VP-16. The efficacy of similar drugs in the rarer pediatric soft tissue sarcomas other than rhabdomyosarcoma and its variants requires prospective randomized trials evaluating histologic grade, tumor size, and nodal status. It has been suggested that the high-grade sarcomas presenting with minimal tumor bulk are most sensitive to combined radiotherapy-chemotherapy, whereas the low-grade sarcomas are more resistant to such therapy. Tumor cell heterogeneity contributes to biologic diversity and response to treatment. Chemotherapy as adjuvant therapy to irradiation is currently recommended and utilized for Ewing's sarcoma with survival rates approaching 80%, and disease-free survival of approximately 75% for those with localized disease. Children with widespread and metastatic disease at presentation fare less well. Although multiple single agents exhibit response rates ranging from 40% to 60%, including cyclophosphamide, Adriamycin, dactinomycin, BCNU, mithramycin, and 5-fluorouracil, new and more effective agents are needed. Controversy regarding the value of multiagent chemotherapy in osteosarcoma has stimulated prospective randomized trials. Evaluation of local control rates as well as sites and occurrence of metastases are essential in assessing the contribution of aggressive combined modality therapy in the pediatric sarcomas. Emphasis on refinement of therapy in determining the risk/benefit ratio from adjuvant chemotherapy in pediatric sarcomas is mandatory. Enhancement of early local reactions is apparent when adjuvant chemotherapy is used with local radiotherapy.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The value of adjuvant chemotherapy in the management of sarcomas in children. 388 37


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