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 C1300 murine neuroblastoma system has been studied to determine its relevance as a chemotherapy model to the human disease. Studies using combination therapy revealed that BCNU/cyclophosphamide combination therapy increased the median lifespan 300% in A/J mice bearing the C1300 tumor. Cyclophosphamide/imidazole carboxamide and adriamycin/imidazole carboxamide combinations were less active, increasing median lifespans 189% and 144%, respectively. Vincristine/bleomycin were inactive even when the schedule was adjusted to coincide with the time of maximum mitoses following vincristine injections. These results suggest the BCNU/cyclophosphamide combination chemotherapy may be effective in human disease.
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PMID:Combination chemotherapy in murine neuroblastoma. 6 76

Cyclophosphamide is used extensively to treat malignancies. A 5-year-old boy with stage IV neuroblastoma is described who developed a fatal syndrome of inappropriate antidiuretic hormone (ADH) secretion after high dose cyclophosphamide therapy.
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PMID:A fatal case of inappropriate ADH secretion induced by cyclophosphamide therapy. 47 99

Clinical chemotherapy in the treatment of neuroblastoma is undergoing further evaluation. Chemotherapeutic agents, cyclophosphamide, vincristine, and hexamethylmelamine, were investigated in a murine neuroblastoma model that, in part, histologically and morphologically resembles the human tumor. The tumor was inoculated subcutaneously (SC), intramuscularly (IM), intraperitoneally (IP), intrarenally (IR). Growth of tumor was observed at all sites, as well as the appearance of metastases. Maximal survival of 32 +/- 1 days was seen (SC) and the minimum was 15 +/- 1 days (IR) (p less than 0.05). Corresponding survival rate for IM was 26 +/- 1 days and IP 21 +/- 1 days. For this reason SC was selected for drug testing. Cyclophosphamide 100 mg/kg/week showed the most favorable results, as determined by autopsy status with fewer tumors and a greater tumor weight decrease over time. This agent also showed a significantly longer survival in comparison to all other drugs (p less than 0.0001). The results with vincristine and hexamethylmelamine in the dose ranges employed differed little from the placebo, except for the finding of a slight decrease in body weight at autopsy.
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PMID:Studies and characterization of a murine neuroblastoma model. 82 82

To gauge the impact of intensified therapy on the survival of infants (younger than 1 year, n = 129) and children (greater than or equal to 1 year of age, n = 275) with neuroblastoma, we analyzed the results of eight successive clinical trials comparing various combinations of antineoplastic drugs, surgery, and radiotherapy. Changes in treatment did not affect the survival of children with involved noncontiguous lymph nodes or distant metastatic disease until the combination of cisplatin and teniposide (CDDP/VM26) was added to a basic regimen of cyclophosphamide and doxorubicin (CTX/DOX). The resulting 4-year survival was 28% +/- 5% (SE) compared with 7% +/- 2% for previous treatments (P less than .001 by the log-rank test). The 4-year survival of infants with metastatic disease was improved by administering CTX/DOX to all patients, reserving CDDP/VM26 for those whose disease was resistant to the former combination: 82% +/- 6% versus 45% +/- 8% in earlier studies; P less than .001. In the subset of infants whose tumors had disseminated to bone or bone marrow at diagnosis, this therapeutic approach increased the probability of long-term survival from 48% +/- 10% to 85% +/- 9% (P = .01). The small group of children over 1 year of age with localized unresectable tumors also fared significantly better with the switch to CTX/DOX chemotherapy (4-year survival, 93% +/- 7% v 42% +/- 13%; P = .02). Multivariate analysis indicated that young age, limited-disease stage, nonadrenal primary site, and intensified treatment were independent predictors of a more favorable outcome. We conclude that substantial advances in the treatment of neuroblastoma have occurred over the past 25 years at this institution. The current overall 4-year survival probability of 57% +/- 4% compares favorably with estimates for most other common solid tumors of childhood.
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PMID:Impact of intensified therapy on clinical outcome in infants and children with neuroblastoma: the St Jude Children's Research Hospital experience, 1962 to 1988. 183 94

The Pediatric Oncology Group (POG) evaluated in a prospective study the hypothesis that patients who had localized, visible residual neuroblastoma without regional lymph node involvement after surgery (POG stage B) have a favorable prognosis when treated with moderate intensive chemotherapy. Eligible patients were initially treated with five courses of Cytoxan (cyclophosphamide; Bristol-Myers Squibb Co., Evansville, IN) and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) followed by surgery (CY/AD +/- surgery). Those patients not achieving a complete remission (CR) crossed over to five courses of cisplatin and teniposide (PL/VM) +/- surgery. Radiation therapy (XRT) was given to selected patients who still were not in CR after the crossover therapy. Of the 61 eligible patients, 38 (62%) patients achieved CR after CY/AD proven by clinical (31) or surgical (seven) evaluation. One (2%) patient in clinical partial remission (PR-C) entered CR without further therapy. Nineteen (31%) patients achieved CR with the following salvage therapies: surgery (five), PL/VM +/- surgery (five) followed by XRT (three) or autologous bone marrow transplant (ABMT) (one) and further courses of CY/AD +/- PL/VM instead of courses of PL/VM (five). The overall CR rate was 95% (58 of 61). Four patients had recurrence of the disease. The probability of being disease-free at 3 years after initial or salvage therapy was estimated at 84% (SE, 5%). The overall prognosis of children older than 1 year and younger than 1 year was similar (P = .26). If, however, the three remission deaths (all younger than 1 year) were censored, there was only one other failure in 32 children younger than one versus seven of 29 children older than 1 year (P = .018). These results confirm the excellent prognosis for patients with POG stage B neuroblastoma and indicate that most patients are curable with CY/AD +/- surgery, and those not achieving CR with this therapy are curable with alternate therapy.
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PMID:Postoperative treatment of nonmetastatic visible residual neuroblastoma: a Pediatric Oncology Group study. 204 58

We have evaluated the role of radiotherapy in providing local control of primary tumors and to palliate metastases from neuroblastoma (NB). Fifty-five children with histologically verified NB were evaluated and treated from 1967 to 1984. In univariate analysis, the actuarial survival of eight children with thoracic primaries (85%) was significantly better than the survival of 39 children with intra-abdominal primaries (35%, p = 0.0287). The survival of 28 children less than or equal to 18 months of age at diagnoses was 73%, whereas 27 children older than 18 months had a survival probability of 10% (p = 0.0001). The survival by Evans stage was: I 100% (2 patients), II 85% (7), III 60% (13), IV 4% (27) and IV-S 100% (6). According to the Pediatric Oncology Group (POG) staging system, the survival was: A 100% (3), B 66% (9), C 66% (9), D 23% (34). A multivariable analysis indicated that the Evans staging system was a more powerful indicator of prognosis than the POG system. The analysis also indicated that Evans stage and patient age were independent determinants of survival. The primary tumor site did not add significant prognostic information beyond these two factors. Children with Stage I disease were treated with surgery alone. Most children with Stages II and III disease were treated with surgery, irradiation, and Cyclophosphamide or Cyclophosphamide plus Vincristine. All seven patients with Stage II disease received post-operative irradiation to the primary tumor and were locally controlled with doses of 4.8 to 26.5 Gy. Eleven of the 13 patients with Stage III disease were irradiated post-operatively. Seven of these 11 patients were locally controlled with doses of 12 to 48.4 Gy. The four Stage III patients with in-field recurrences were older children with large radiotherapy fields and/or low doses administered. The Radiation Therapy Oncology Group pain score system was used to evaluate response of painful bony metastases to irradiation. A response was observed in 65% of the sites irradiated. A response was observed at 67% of the soft tissue metastases irradiated. Hepatomegaly causing respiratory embarrassment or inferior vena cava obstruction was treated with irradiation in seven patients. All patients responded with doses ranging from 5 to 24.4 Gy. Five of the 17 children who survived for more than 5 years following treatment had significant scoliosis or kyphosis secondary to vertebral body abnormalities in irradiated bones. All five children were irradiated at a young age with megavoltage equipment.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Radiation therapy in the management of neuroblastoma: the Duke University Medical Center experience 1967-1984. 242 88

Results of two consecutive treatment programs for advanced neuroblastoma, including sequential hemibody irradiation, are analyzed and compared. The first treatment program (I-TP) included one single-fraction (7 Gy) irradiation to the upper and lower halves of the body as consolidation of remission achieved by previous chemotherapy with CDDP and VP16. A fractionated technique (2 Gy daily for 4 consecutive days to each hemibody) was used in the second treatment program (II-TP) for children in remission following a combination of CDDP + VP16 and ADM + VCR + CTX. In both treatment programs, chemotherapy was continued according to the same pre-radiation regimen following the two sessions of hemibody irradiation. Overall response rate to pre-radiation chemotherapy was 84% and 60% for I-TP and II-TP, respectively. Thirty-month overall progression-free survival was 0 for I-TP and 20% for II-TP. No treatment-related fatalities occurred. In the subsets of patients who reached complete or good partial remission during the pre-radiation chemotherapeutic phase, 30-month progression-free survival in I-TP and II-TP was 0 and 33%, respectively. The role of fractionated hemibody irradiation in prolonging the progression-free survival can be inferred.
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PMID:Advanced neuroblastoma: results of two treatment programs including sequential hemibody irradiation. 267 76

Four cloned murine neuroblastomas were implanted intramuscularly into the left thigh of adult A/Jax mice. Cyclophosphamide, cisplatin, adriamycin, imidazole carboxamide, and vincristine were administered intraperitoneally, in a dose of one third to one fourth of a median lethal dose, every week after the implantation until all the mice died. The effects of continuous long-term chemotherapy, particularly on clonal differences, were then assessed. Cyclophosphamide was most effective for four murine neuroblastomas, and cisplatin was the next most effective drug. Cisplatin was not effective in the NS-20 cell line, a cholinergic cloned neuroblastoma. The C 1300 cell line (wild type) was tolerant to adriamycin, imidazole carboxamide, and vincristine. The N-18 cell line (an inactive clone) exhibited tolerance of adriamycin and imidazole carboxamide. In the N1E-115 cell line, an adrenergic clone, tumor growth was inhibited by all the drugs given. We conclude from this study that drug sensitivity differs with the clone, and that there are clones resistant to each drug.
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PMID:Different clonal drug sensitivity of murine neuroblastoma cells in vivo. 323 66

High dose chemo-radiotherapy followed by autologous bone marrow transplantation (ABMT) is known to be an effective treatment in stage IV neuroblastoma (NB). Since October '84, 19 children with NB (12 relapsed or resistant: Group A; 7 in first CR: Group B) received ablative therapy (AT) consisting of VCR (4 mg/mg), L-PAM (140 mg/mg) and fractionated TBI (1000 Rads). Induction strategy at diagnosis or at relapse included high dose Peptichemio, 2-3 cycles of Vincristine-Cyclophosphamide--high dose Platinum and surgery. Bone marrow was harvested after 2 evaluation proved negative by cytomorphology, histology and immunofluorescence. Mononuclear cells (median 6.7 x 10(7)/kg) were cryopreserved and reinfused without purging. At the time of AT in Group A8 children were in CR, 4 had minimal diseases; in Group B 6 were in CR and one in PR. One toxicity-related death occurred on day 7 in a child in first CR; median duration of granulocytopenia 0.5 x 10(9)/l and thrombocytopenia less than 50 x 10(9)/l were 20 days (R: 9-40) and 27 days (R: 11-51) respectively. Persistent immune thrombocytopenia occurred in 4 children. Fever higher tha 38 degrees C developed in all patients: sepsis was documented in 6 patients. Extramedullary toxicity was moderate: GI tract was the most affected. Two out of 5 children who received AT having residual disease achieved CR; relapse or progression of disease occurred in all these patients. Four out of 8 children in second or subsequent CR and 4 out of 5 in first CR are alive and well at 3-12 months (median 7).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Total body irradiation, vincristine in continuous infusion and high-dose melphalan with transplant of autologous bone marrow in the treatment of neuroblastoma]. 330 21

A four-year-old boy with stage IV neuroblastoma was treated using the group study protocol of the Tohoku area for advanced neuroblastoma, consisting of DTIC, CPA, VCR, CDDP and VM-26, as a result of which had obtained complete remission. However, he had severe hemorrhagic cystitis after administration of CPA. He was treated with the usual therapy, but symptoms such as hematuria, pollakiuria and miction pain were not improved. We then tried bladder irrigation with prostaglandin E2. Half a milligram of PGE2 in 100 ml of physiological saline solution was instilled into the bladder and left in situ for 3 hours. The patient was free of symptoms on the day following the therapy. Local therapy with PGE2 thus seems very useful for cyclophosphamide-induced cystitis.
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PMID:[Bladder irrigation with prostaglandin E2 in cyclophosphamide-induced hemorrhagic cystitis]. 342 44


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