Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The observed response of [131I]metaiodobenzylguanidine (131I-MIBG) therapy in advanced neuroblastoma after conventional therapy had failed, the noninvasiveness of the procedure, and the high metabolic activity of untreated tumors led to a new protocol to use 131I-MIBG therapy in newly diagnosed patients instead of combination chemotherapy prior to surgery. The objectives of this study are to improve the overall outcome of patients with neuroblastoma by introducing 131I-MIBG therapy as the first therapy in the treatment schedule, in order to reduce the tumor volume, enabling adequate surgical resection and avoiding toxicity and the induction of early drug resistance. The advantages of this approach are that the child's general condition is unaffected before surgical resection is performed and that chemotherapy is reserved to treat minimal residual disease. So far, 13 patients with inoperable neuroblastoma (stage III and IV) were treated with 131I-MIBG initially and then submitted to surgery. More than 50% decrease of the volume of the primary tumor was noted in 7 of 10 evaluable patients; 8 patients have so far been operated with complete resection in 2, greater than 95% resection in 5 and 80% resection in one patient. Three patients are still undergoing 131I-MIBG treatment. The toxicity of 131I-MIBG de novo is in contrast with the previous experience of 131I-MIBG therapy after conventional therapy: only 4 patients had thrombocytopenia and only 1 of 7 patients with bone marrow involvement developed bone marrow depression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preoperative [131I]metaiodobenzylguanidine therapy of neuroblastoma at diagnosis ("MIBG de novo"). 182 28

To find a treatment that may be effective against micrometastases of advanced, stage III or IV neuroblastoma, [125I]metaiodobenzylguanidine (125I-MIBG) was used in a phase I toxicity trial. In seven patients, thrombocytopenia was encountered with absorbed whole body doses of 85-135 rad from 125I-MIBG, but the dosimetry was imprecise in predicting bone marrow injury. Three patients survived for over one year, results that may indicate efficacy of 125I-MIBG therapy.
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PMID:Treatment of neuroblastoma with [125I]metaiodobenzylguanidine. 182 30

From February 1986 to December 1988, 31 children with advanced pretreated neuroblastoma were treated with 131-I meta-Iodobenzylguanidine (131-MIBG). Thirteen children had been resistant to first-line therapy, three had suffered a local relapse, and fourteen had suffered a disseminated relapse without over bone marrow infiltration. One child was treated initially because of resistance to first-line therapy, and subsequently for a local relapse. A total of 72 courses of 131-MIBG was administered, with doses ranging from 2.8 to 6.0 GBq (median, 3.7 GBq). One child received five courses, two four courses, 13 three courses, four two courses, and 12 one course of 131-MIBG. The most common toxic effect was thrombocytopenia, with a platelet level of less than 50,000/cmm occurring after 19 of 60 evaluable courses. A leukocyte count less than 1000/cmm was seen only once. There were six major responses (two complete) lasting 4 to 9 months, and two minor responses lasting longer than 38 and 44 months. Responses were seen more commonly in children whose only lesion was a residual primary tumor and in children who had not been pretreated who experienced disseminated relapse. Further studies of the role of 131-I meta-Iodobenzylguanidine in treatment of neuroblastoma are needed.
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PMID:Treatment of advanced neuroblastoma with I-131 meta-iodobenzylguanidine. 199 Dec 64

Carboplatin was administered at 1,000 mg/m2/course in combination with etoposide at 300 mg/m2/course to 23 patients aged 5 months to 16 years. Five patients were affected by neuroblastoma, four by CNS tumors, three by Ewing's sarcoma, two by rhabdomyosarcoma, two by malignant teratoma, two by Wilms' tumor, two by head and neck carcinoma, one by hepatoblastoma, one by synovial sarcoma, and one by Langerhans-cell histiocytosis. Eleven patients were pretreated, seven of them with high-dose cisplatin. The overall response rate was 7/11 (64%) for pretreated and 10/12 (83%) for previously untreated patients. Myelosuppression was the main side effect, with anemia and thrombocytopenia more pronounced than leukopenia. Gastrointestinal toxicity and ototoxicity were very mild; nephrotoxicity and neurotoxicity other than hearing loss were not observed. In children with malignant tumors, the therapeutic activity of carboplatin at high doses, even in combination chemotherapy, deserves further studies.
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PMID:A pilot study of high-dose carboplatin and pulsed etoposide in the treatment of childhood solid tumors. 220 54

Fifty-one children, aged from 15 months to 13 years 5 months with metastatic neuroblastoma presenting sequentially at the participating institutions received four 3 to 4 weekly courses of high dose multiagent chemotherapy. High dose cisplatin (200 mg m-2) combined with etoposide (500 mg m-2), HIPE, was alternated with ifosfamide (9 g m-2), vincristine (1.5 mg m-2), and adriamycin (60 mg m-1), IVAd. Disease status was re-evaluated 3 to 4 weeks after the fourth course and the response classified according to the International Neuroblastoma Response Criteria (INRC). The overall response rate in evaluable patients was 55% and response rates by site were: bone marrow 67% (complete response 47%); bone scan 68%; primary tumour 61%, and urinary catecholamine metabolites (VMA/HVA) 95%. Serial 51Cr EDTA renal clearance studies showed a glomerular filtration rate (GFR) decline in 40% of patients but in only seven cases to below 50% of the pretreatment value. There was no instance of renal failure during induction, though two patients developed severe renal failure following 'megatherapy' given to consolidate remission. Serial audiometry showed a significant decline in hearing at frequencies above 2,000 Hz in 37% of children but at or below 2,000 Hz in only 17%. Neutropenia and thrombocytopenia were severe and intravenous antibiotics were required after 30% of courses. Each of two treatment-related deaths occurred during pancytopenia following courses of IVAd. Complete, or greater than 90%, removal of primary site tumour was possible in 70% of cases following this induction regimen and 75% of patients proceeded to elective megatherapy within a median time of 24 weeks after diagnosis. This short intensive induction programme is highly effective at achieving cytoreduction, enabling early surgery and early megatherapy procedures. It is, however, too early to draw firm conclusions about the impact of this approach to treatment on the cure rate.
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PMID:Short duration, high dose, alternating chemotherapy in metastatic neuroblastoma. (ENSG 3C induction regimen). The European Neuroblastoma Study Group. 238 51

Three children with Stage III neuroblastoma were treated with [125I]MIBG in a phase I toxicity study. Concepts of the treatment were: in small tumors, the absorbed dose of radiation from MIBG labeled with 131I is reduced but the absorbed dose from [125I]MIBG is less affected; and many recurrences of neuroblastoma arise from small tumors. Two patients exhibited only modest thrombocytopenia and leukopenia, the most sensitive indices of radiation toxicity, after receiving 261 and 407 mCi, and 83 and 104 rad of whole-body radiation. One patient died of progressive neuroblastoma; the other two patients have stable disease over 30 mo after treatment. Per millicurie given, [125I]MIBG imparts about one-fourth the radiation dose of [131I]MIBG to the whole body. Iodine-125-MIBG can be given in doses that impart over 100 rad of whole-body radiation and that exceed 400 mCi before toxicity becomes limiting, even in small children.
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PMID:Iodine-125-MIBG to treat neuroblastoma: preliminary report. 199 43

Therapeutic efficacy and toxicity were evaluated in 28 children with acute lymphoblastic leukemia, in ten with acute nonlymphoblastic leukemia (ANLL), and in 13 with metastatic neuroblastoma. All were refractory to standard chemotherapeutic agents and 25 were refractory to an investigational drug. The initial dose was 12 mg/m2/day and was based on an established maximal dose tolerated in adults. This dose was found to be intolerable in 5 of 5 children with leukemia. Similarly an initial dose of 9 mg/m2/day was intolerable in 4 of 5 patients with leukemia. The starting dose in the next 28 children with leukemia or neuroblastoma was 3 mg/m2. This drug was gradually increased to the highest tolerated dose by 3-mg/m2 increments. Fifteen children with acute lymphoblastic leukemia, 3 children with ANLL, and 2 children with neuroblastoma received the drug daily. Seven patients with ANLL and 7 patients with neuroblastoma received the drug biweekly. Seventeen patients with acute lymphoblastic leukemia, 6 patients with ANLL, and 5 patients with neuroblastoma had an adequate trial of the drug. An adequate trial was defined as a minimum of 5 weeks of therapy unless progressive disease developed. Side effects of the drug were striking and included fever, hypotension, myalgia, bone pain, arthralgia, arthritis, abdominal pain, liver toxicity, thrombocytopenia, and neurotoxicity. No complete remission occurred although interferon levels above 100 units/ml were induced in nearly 50% of the patients.
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PMID:Phase II trial of a complex polyriboinosinic-polyribocytidylic acid with poly-L-lysine and carboxymethyl cellulose in the treatment of children with acute leukemia and neuroblastoma: a report from the Children's Cancer Study Group. 241 2

A Phase II study of poly(I,C)-LC was performed in 28 children and adolescents with acute lymphoblastic leukemia (ALL), 10 with acute nonlymphoblastic leukemia (ANLL), and 13 with metastatic neuroblastoma. All were refractory to standard chemotherapeutic agents and 25 to an investigational drug. Initial doses of 12 mg/m2 and 9 mg/m2 were intolerable. However, 9 mg/m2 was tolerable in the majority of patients when the drug was started at 3 mg/m2 and increased by 3 mg/m2 increments. Fifteen children with ALL, three with ANLL, and two with neuroblastoma received the drug daily. Seven patients with ANLL and seven children with neuroblastoma received the drug biweekly. Twenty-eight patients received an adequate trial, which was defined as a minimum of 5 weeks at the maximal tolerated dose, unless there was progressive disease at the maximal tolerated dose. Side effects of the drug were striking, and included fever, hypotension, myalgia, bone pain, arthralgia, arthritis, abdominal pain, liver toxicity, thrombocytopenia, and neurotoxicity. No complete remissions occurred in spite of interferon levels above 100 U in nearly 50% of patients.
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PMID:Phase II trial of poly(I,C)-LC, an interferon inducer, in the treatment of children with acute leukemia and neuroblastoma: a report from the Children's Cancer Study Group. 241 84

An acutely ill 6-month-old female infant presented with massive hepatomegaly, accompanied by severe anemia with peripheral normoblastemia and thrombocytopenia. Bone marrow examination revealed erythroid hyperplasia with gross erythroid dysplasia, reduced granulocytic precursors, and virtually absent megakaryocytes. The bone marrow also contained completely necrotic cells occurring in clumps as well as singly. The appearances suggested bone marrow involvement by neuroblastoma. Accordingly, combination chemotherapy was instituted and laparotomy was performed as soon as her clinical condition had improved. Left adrenalectomy was carried out, because a small adrenal nodule of ganglioneuroma was present. Liver biopsy showed expansion of portal tracts by loose fibrous connective tissue containing hemosiderin deposits and some degenerate cellular debris, consistent with areas of involuted metastatic neuroblastoma. Complete recovery followed, and subsequent bone marrow examination was entirely normal. It is thought that the dyserythropoiesis probably resulted from the release of toxic metabolites from regressing neuroblastoma.
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PMID:Transient dyserythropoiesis occurring during the involutionary phase of stage IV-S neuroblastoma. 271 38

The selective uptake and accumulation of 131J-Metaiodobenzylguanidine in neuroblastoma cells in vivo may be utilized for targeted irradiation. The experience with 32 neuroblastoma patients refractory to conventional high dose chemotherapy is reported. At diagnosis 8 patients had Evans stage III and 22 stage IV. 11/32 experienced recurrences after complete tumor disappearance and before mIBG treatment, 16/32 progressed from residual or nonresponding tumor and in 3/32 insufficient tumor regression by chemotherapy was observed. 2 children received one mIBG course each with no evidence of disease. Mean applied activity was 128 mCi per course (35-300 mCi), 360 mCi per patient (80-1033 mCi) and 19.2 mCi/kg per patient (3.2-37.9 mCi/kg), respectively. A total of 84 courses was given (mean 2.6 per patient). Pain relief was noticed in 14/14 patients with bone pain. Complete or very good partial remission was achieved in 5/32, partial remission in 11/32 and stable disease in 6/32 patients. In 8 children progression occurred and 2 patients were not evoluable. 20 children died, 12 are still alive (6 patients with initial stage IV, 6 with stage III disease). Main side effect was transient thrombocytopenia, which became more severe with increasing number of courses. We conclude that mIBG treatment is effective in some patients with refractory neuroblastoma and may be utilized in the future as front line therapy for patients achieving only incomplete regressions after high dose chemotherapy.
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PMID:[131(I)-meta-iodobenzylguanidine treatment of 32 children with therapy-refractory neuroblastoma]. 306 60


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