pirarubicin and Neuroblastoma

The authors present a case of 3-year-old female with Stage 4 neuroblastoma originating from the left adrenal gland. Biopsy of the left adrenal tumor showed neuroblastoma. After three courses of chemotherapy, the left adrenal gland including the left adrenal tumor was surgically removed. Pathological findings of the resected tumor revealed that most of the neuroblastoma tissues changed to pheochromocytoma-like cells. The tumor cells were arranged in well-defined nests surrounded by a delicate fibrovascular stroma and had granular eosinophilic cytoplasm, and round to oval nuclei. Immunohistological analysis of the biopsy samples showed strongly positive Ganglioside GD2-staining cells, whereas almost all of the tumor cells in the resected specimen were Ganglioside GD2-negative; cells were very weakly stained. The authors suggest that a part of the neuroblastoma in the left adrenal gland exhibited unusual differentiation toward pheochromocytic lineage Ganglioside GD2-negative neuroblastoma in a patient who had been treated with intensive chemotherapy.

Topics: Adrenal Gland Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cell Differentiation; Child, Preschool; Cisplatin; Cyclophosphamide; Doxorubicin; Female; Humans; Immunohistochemistry; Neoplasms, Second Primary; Neuroblastoma; Pheochromocytoma; Vincristine

Autologous bone marrow transplantation (ABMT) and peripheral blood stem cell transplantation (PBSCT) are increasingly used to support high-dose chemotherapy for solid tumors of childhood. In this review we described practical aspects of myeloablative chemotherapy rescued by ABMT, PBSCT or combination of ABMT and PBSCT for the treatment of children with high-risk solid tumor, involving our experiences in 15 cases. Indication, method of harvesting bone marrow and peripheral blood stem cells, cryopreservation, transplantation, selection of anti-neoplastic agents for preconditioning, nutritional and G-CSF support, engraftment and outcomes for prognosis were discussed. In comparing the engraftment of stem cells between ABMT and PBSCT, the acceleration of platelet and erythrocyte recovery is less impressive, although there is a tendency to more rapid recovery of granulocyte in PBSCT group. The outcomes are distinctly improved only in patients who showed complete remission after induction chemotherapy, radiation and surgical excision. A better prognosis will be conferred especially in neuroblastoma and entities of small round cell tumor. It is noteworthy that relapses can occur as distant metastasis considerable years after complete clinical remission. This may be largely contributed by contaminated malignant cells in both harvested bone marrow and peripheral blood stem cells. There is no significant difference between the relapse rates after ABMT and PBSCT.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Purging; Bone Marrow Transplantation; Carboplatin; Child; Combined Modality Therapy; Cryopreservation; Doxorubicin; Etoposide; Hematopoietic Stem Cell Transplantation; Humans; Kidney Neoplasms; Neoplasms; Neuroblastoma; Rhabdomyosarcoma; Wilms Tumor

One hundred and ten patients with advanced neuroblastoma were treated with the protocol of the Study Group of Japan between January 1985 and March 1991. Patients received six cyclic courses of regimen A1, consisting of cyclophosphamide (1,200 mg/m2), vincristine (1.5 mg/m2), tetrahydropyranyl adriamycin (40 mg/m2), and cisplatin (90 mg/m2). Primary tumors and regional lymph node metastases were removed some time during the first six cycles of regimen A1. After six cycles of A1, the patients were divided into three groups. Patients in group 1 received alternating treatment with regimen B (cyclophosphamide and ACNU) and intensified A1, and those in group 2 were treated with alternating administration of regimen C (cyclophosphamide and DTIC) and intensified A1. Patients in group 3 were treated with supralethal therapy and bone marrow transplantation (BMT). Event-free survival rates at five years were 38.8% in the chemotherapy group (groups 1 and 2) and 50.0% in the transplant group (group 3). Because of the study design that was not in truly randomized fashion and because of the small number of patients in each risk group, it is indicated, though not concluded, that the transplant group had a better prognosis than the chemotherapy group in the cases with stage III disease or with amplified N-myc oncogene, based on the statistical calculations. Differences in survival rates for patients who underwent BMT when complete remission (CR) was achieved and for those who achieved CR but who did not undergo marrow transplant were statistically insignificant. BMT-related death occurred in 3 of 31 cases (9.7%) undergoing marrow transplant, and the causes of the death included hemorrhagic pneumonia, myocardial disturbance and hemorrhagic uremia.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Child; Child, Preschool; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Dacarbazine; Disease-Free Survival; Doxorubicin; Humans; Infant; Japan; Neuroblastoma; Nimustine; Prognosis; Remission Induction; Risk Factors; Survival Rate; Vincristine

The role of surgery was evaluated in 19 stage III and 102 stage IV neuroblastoma patients, all of whom were treated with intensive induction chemotherapy by the Study Group of Japan between January 1985 and March 1990. For stage III neuroblastoma, surgical intervention at the primary site was performed in 18 of the 19 patients, 9 during and 9 after the first three cycles of A1 regimen, consisting of high-dose cyclophosphamide, vincristine, THP-adriamycin, and cis-platinum. Gross complete resection of primary tumor and regional lymph nodes was feasible in 17 of the 19 patients (89%), and the survival rate for the 17 patients were 79%, 70%, and 70% at 2 years, 3 years, and 4 years, respectively. For stage IV, surgical intervention at the primary site was performed in 92 of the 102 patients (90%): 30 cases during the first 3 cycles of A1 chemotherapy and 62 cases after that, with gross complete resection accomplished in 81 of the 102 patients (79%). The 81 patients with gross complete resection achieved had a better prognosis than those 11 patients with partial resection (P less than .05). Overall survival rate was 62% at 2 years for 27 patients who underwent complete resection after 3 cycles of A1 when resolution of all metastases was obtained, whereas the survival was 52% at 2 years for 31 patients who similarly underwent complete resection but when evidence of persistent metastases was present. Patients in whom the ipsilateral kidney was preserved at surgery had an outcome superior to that of those with associated nephrectomy (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cyclophosphamide; Doxorubicin; Humans; Infant; Japan; Kidney Neoplasms; Neoplasm Staging; Nephrectomy; Neuroblastoma; Preoperative Care; Vincristine

The present study sought to reduce the incidence of treatment complications of low-risk neuroblastoma by using image-defined risk factors (IDRFs) to inform the timing of surgical resection.. Eligible patients included children (<18 years of age) with stage 1 or 2 disease, children (<365 days of age) with stage 3 disease, and infants with stage 4S disease. In IDRF-negative cases, treatment was completed with surgical resection alone. In IDRF-positive cases, the timing of surgery was determined based on the IDRFs after low-dose chemotherapy with 2-3 of the following four drugs: vincristine, cyclophosphamide, pirarubicin, and carboplatin. The outcome measures were overall survival, progression-free survival, and adverse events. This study was registered with the UMIN Clinical Trials Registry (number 000004355).. Of the 60 patients screened between 2010 and 2013, 58 eligible patients were enrolled; 32 were identified as IDRF negative at diagnosis while 26 were identified as IDRF positive and underwent induction chemotherapy. The 3-year overall and progression-free survival rates of the 58 patients were 100% and 82.8% (95% confidence interval: 70.3-90.3), respectively. Neutropenia was the most frequently reported grade 3 or 4 chemotherapy-related form of toxicity (41.7%). With regard to surgical complications, 2.5% of all patients developed pleural effusion and ascites as early complications, while only 2.5% developed renal atrophy as a long-term complication. No fatal toxicities were observed.. Using IDRFs to inform surgical decision making for the treatment of low-risk neuroblastoma improved prognosis and reduced the incidence of long-term complications.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Chemotherapy-Induced Febrile Neutropenia; Child; Child, Preschool; Clinical Decision-Making; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Female; Ganglioneuroblastoma; Humans; Infant; Infant, Newborn; Japan; Kaplan-Meier Estimate; Magnetic Resonance Imaging; Male; Neuroblastoma; Pleural Effusion; Postoperative Complications; Progression-Free Survival; Prospective Studies; Risk Factors; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Vascular Diseases; Vincristine

Water-soluble N-(2-hydroxypropyl)methacrylamide copolymer conjugates bearing the anticancer drugs doxorubicin (Dox) or pirarubicin (THP), P-gp inhibitors derived from reversin 121 (REV) or ritonavir (RIT)), or both anticancer drug and P-gp inhibitor were designed and synthesized. All biologically active molecules were attached to the polymer carrier via pH-sensitive spacer enabling controlled release in mild acidic environment modeling endosomes and lysosomes of tumor cells. The cytotoxicity of the conjugates against three sensitive and Dox-resistant neuroblastoma (NB) cell lines, applied alone or in combination, was studied in vitro. All conjugates containing THP displayed higher cytotoxicity against all three Dox-resistant NB cell lines compared with the corresponding Dox-containing conjugates. Furthermore, the cytotoxicity of conjugates containing both drug and P-gp inhibitor was up to 10 times higher than that of the conjugate containing only drug. In general, the polymer-drug conjugates showed higher cytotoxicity when conjugates containing inhibitors were added 8 or 16h prior to treatment compared with conjugates bearing both the inhibitor and the drug. The difference in cytotoxicity was more pronounced at the 16-h time point. Moreover, higher inhibitor:drug ratios resulted in higher cytotoxicity. The cytotoxicity of the polymer-drug used in combination with polymer P-gp inhibitor was up to 84 times higher than that of the polymer-drug alone.

Topics: Antibiotics, Antineoplastic; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cell Line, Tumor; Cell Survival; Doxorubicin; Drug Liberation; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Methacrylates; Neuroblastoma; Oligopeptides; Ritonavir

The aim of this study was to evaluate the effectiveness of post-surgical chemotherapy for infants with localized neuroblastoma without MYCN amplification (MNA), and determine whether risk classification using MNA is reasonable.. Four hundred and fourteen eligible patients were registered between 1998 and 2004. Resectable patients in stage 1 and 2A/2B were treated by surgical resection only. Unresectable patients in stage 3 without MNA received either 6 cycles of regimen A or 3 cycles of regimen A plus 3 cycles of regimen C2; regimen A consisted of low doses of cyclophosphamide and vincristine and regimen C consisted of cyclophosphamide, vincristine and pirarubicin before surgical resection. The resectable and unresectable patients were randomly selected to receive post-surgical chemotherapy. The patients with MNA received intensive chemotherapy regimen D2, consisting of cyclophosphamide, vincristine, pirarubicin and cisplatin, and some of them received high-dose chemotherapy with stem cell transplantation.. The 5-year event-free survival (5-EFS) rates of stage 1 and 2A/2B patients without MNA were 97.2 and 89.0% respectively (p = 0.02). A total of 31 patients in stage 3 without MNA received post-surgical chemotherapy, and 30 patients did not. The 5-EFS rates of these two groups (96.0 and 96.2%, respectively) were not significantly different (p = 0.869). The 5-EFS rate for localized patients with MNA (n = 6) was 50.0%, and that of patients without MNA was 95.0% (p < 0.001).. Post-surgical chemotherapy was therefore unnecessary for localized patients without MNA. This treatment strategy using MNA is considered to be appropriate in infants.

Topics: Cisplatin; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Gene Expression Regulation, Neoplastic; Humans; Infant; N-Myc Proto-Oncogene Protein; Neoplasm Staging; Neuroblastoma; Nuclear Proteins; Oncogene Proteins; Prognosis; Vincristine

Three pediatric patients with infratentorial metastatic non-epithelial malignant brain tumors were successfully treated by radical surgical resection followed by aggressive radiochemotherapy. One patient with neuroblastoma and two with rhabdomyosarcoma were successfully treated by first line multimodal treatments, but developed infratentorial metastasis after several months of remission. All patients revealed intracranial metastases manifesting as rapidly progressing neurological symptoms caused by mass effect in the posterior fossa. Radical surgical resection was performed without morbidity. The patients were then treated by adjuvant radiochemotherapy with or without autologous peripheral blood stem cell transplantation, resulting in complete remission. Two patients developed extracranial recurrences 4 months after the treatments for intracranial metastases. One patient was treated by second high-dose chemotherapy with allogeneic cord blood transplantation, again resulting in complete remission. Another patient was treated by second chemotherapy and maintaining stable disease. The other patient maintained complete remission. All three patients were alive without neurological deficit for 8, 11, and 12 months after diagnosis of brain metastasis. Patients with infratentorial brain metastases of highly malignant pediatric non-epithelial tumors are in a severe clinical state, but still can have longer and useful lives with aggressive multimodal treatments combined with radical surgical resection.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Camptothecin; Carboplatin; Chemotherapy, Adjuvant; Child; Child, Preschool; Cisplatin; Combined Modality Therapy; Dactinomycin; Doxorubicin; Etoposide; Humans; Ifosfamide; Infant; Infratentorial Neoplasms; Irinotecan; Melphalan; Neoplasm Metastasis; Neuroblastoma; Rhabdomyosarcoma; Thiotepa; Topotecan; Vincristine

The local control of neuroblastoma is a very important treatment consideration. We describe a patient who received high-dose rate 60Co remote after loading system treatment for local control of recurrent neuroblastoma and discuss the efficacy of high-dose rate 60Co remote after loading system treatment.

Topics: Abdominal Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Brachytherapy; Busulfan; Carboplatin; Cisplatin; Cobalt Radioisotopes; Combined Modality Therapy; Cord Blood Stem Cell Transplantation; Cyclophosphamide; Cytarabine; Doxorubicin; Etoposide; Humans; Ifosfamide; Infant; Male; Melphalan; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neuroblastoma; Peripheral Blood Stem Cell Transplantation; Radiotherapy Dosage; Radiotherapy, Adjuvant; Remission Induction; Vidarabine; Vincristine

To investigate whether neuroblastoma cells LA-N-6 express Foxp3 and whether the expression of Foxp3 is sensitive to chemotherapy by cyclophosvnamide (CTX)and pirarubicin (THP).. Expression of Foxp3 on LA-N-6 cells was examined by flow cytometry analysis. The dose-effects of chemotherapy drugs including CTX and THP on LA-N-6 cells were investigated by MTT assay. The effects of CTX and THP on Foxp3 expression were examined by flow cytometry and real-time PCR assays.. Flow cytometry analysis showed that LA-N-6 cells expressed Foxp3 at a high level. At sub-optimal concentration, chemotherapy drugs CTX and THP significantly down-regulated expression of Foxp3 on LA-N-6 cells at protein level (P<0.05). CTX also decreased the expression of Foxp3 at mRNA level (P<0.05). CONCLSUSIONS: Neuroblastoma cells LA-N-6 express Foxp3 at a high level, which can be suppressed by chemotherapy drugs CTX and THP. These data suggest that chemotherapy might suppress the growth and metastasis of tumor cells partially through inhibiting the expression of Foxp3.

Topics: Antineoplastic Agents; Cell Line, Tumor; Cyclophosphamide; Doxorubicin; Flow Cytometry; Forkhead Transcription Factors; Humans; Neuroblastoma; Reverse Transcriptase Polymerase Chain Reaction

The aim of this study was to study the prognostic significance of circulating tumor cells (CTC) and the appropriate indications for aggressive surgery in advanced neuroblastoma.. Micrometastasis was sequentially explored using our reverse transcriptase-polymerase chain reaction method in 29 neuroblastoma patients (International Neuroblastoma Staging System stage 4, n = 24; stage 3, n = 5) who treated at our department with the united chemotherapeutic regimen since 1991. Their medical records and detection of CTC and/or the bone marrow micrometastasis were retrospectively reviewed then analyzed statistically.. The overall survival rate was 58.6% (17/29). Circulating tumor cells were detected in 55.6% of the stage 4 patients, and all deaths were related to systemic metastases in the CTC-positive patients. The detection of CTC scarcely associated with MYCN amplification. In the patients showing MYCN amplification but no CTC, all deaths were related to local relapse or chemotherapy-associated complications. The survival rate was not significantly different between the patients with and without MYCN amplification (56.8% vs 52.7%). However, it was significantly lower in the patients with CTC and/or persistent bone marrow micrometastasis compared to those without detectable micrometastasis (33.8% vs 87.5%; P < .05).. The presence of CTC and/or persistent micrometastasis may indicate a significantly high risk, regardless of MYCN amplification. Patients with MYCN amplification but no micrometastasis would be most benefited by highly intensive surgery.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bone Marrow Neoplasms; Child, Preschool; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Etoposide; Female; Genes, myc; Hematopoietic Stem Cell Transplantation; Humans; Infant; Kaplan-Meier Estimate; Male; Neoplasm Staging; Neoplastic Cells, Circulating; Neuroblastoma; Prognosis; Radiotherapy, Adjuvant; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; Vincristine

Neuroblastoma is the most common extracranial solid tumor of childhood, and iodine-131-metaiodobenzylguanidine (MIBG) therapy is a new approach for grade IV neuroblastoma. We describe the case history of a 3-year-old girl with recurrent neuroblastoma who received MIBG therapy with reduced-intensity allogeneic stem cell transplantation (RIST) because of an extensive bone marrow involvement. The post-transplant course was uneventful and complete chimerism was obtained. Neither acute nor chronic graft-versus-host disease (GVHD) was observed. The patient remained in remission for 3 months after RIST until the second relapse. MIBG therapy combined with RIST warrants further trials.

Topics: 3-Iodobenzylguanidine; Adrenal Gland Neoplasms; Adrenalectomy; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Camptothecin; Child, Preschool; Cisplatin; Combined Modality Therapy; Cranial Irradiation; Cyclophosphamide; Doxorubicin; Etoposide; Fatal Outcome; Female; Humans; Iodine Radioisotopes; Irinotecan; Neuroblastoma; Recurrence; Salvage Therapy; Transplantation Conditioning; Transplantation, Autologous; Transplantation, Homologous; Vincristine

Patients with high-risk neuroblastoma who have multiple copies of MYCN fare much worse than do those without MYCN amplification; however, it has not been clarified whether intensified chemotherapy with or without blood stem cell transplantation can alter the extremely poor prognosis of patients with amplified MYCN.. Between 1985 and 1999, 301 patients older than age 12 months with stage 4 neuroblastoma were treated. From January 1985 to February 1991, 80 patients with stage 4 neuroblastoma with and without MYCN amplification uniformly received induction chemotherapy with regimen A(1) (cyclophosphamide 1,200 mg/m(2) and vincristine 1.5 mg/m(2) on day 1, tetra-hydropyranyl [THP]-Adriamycin 40 mg/m(2) on day 3, and cisplatin 90 mg/m(2) on day 5). Among 22 patients with MYCN amplification, nine (40.9%) achieved a complete remission and seven (31.8%) underwent stem cell transplantation. Of 58 patients without MYCN amplification, 43 (74.1%) achieved a complete remission and 14 (24.1%) underwent stem cell transplantation. The 5-year relapse-free survival rates were 23.2% for stage 4 patients with MYCN amplification and 33.3% for those without MYCN amplification (P = 0.029); the 5-year overall survival rates were 32.8% for stage 4 patients with MYCN amplification and 42.8% for those without MYCN amplification (P > 0.05). From March 1991 to June 1998, patients with stage 4 neuroblastoma who had 10 or more copies of MYCN were treated with regimen A(3) (cyclophosphamide 1,200 mg/m(2) per day on days 1 and 2, THP-Adriamycin 40 mg/m(2) on day 3, etoposide 100 mg/m(2) per day on days 1 to 5, and cisplatin 25 mg/m(2) per day on days 1 to 5); those with fewer than 10 copies of MYCN received regimen new A (cyclophosphamide 1,200 mg/m on day 1, THP-Adriamycin 40 mg/m on day 3, etoposide 100 mg/m per day on days 1 to 5, and cisplatin 90 mg/m on day 5), which is similar in intensity to regimen A. Among 88 patients with MYCN amplification, 63 (71.6%) achieved a complete remission and 63 (71.68%) underwent stem cell transplantation. Of 133 patients without MYCN amplification, 93 (69.9%) achieved a complete remission and 71 (53.4%) underwent stem cell transplantation. The 5-year relapse-free survival rates were 36.0% for stage 4 patients with MYCN amplification and 32.2% for those without MYCN amplification (P > 0.05), the 5-year overall survival rates were 34.0% for stage 4 patients with MYCN amplification and 38.9% for those without MYCN amplification (P > 0.05). The difference in relapse-free survival rates was significantly different (P = 0.003) between patients with MYCN-amplified tumor treated before (regimen A(1)) versus after 1991 (regimen A(3)).. With the use of the more intensive induction regimen A plus blood stem cell transplantation for MYCN-amplified patients, survival curves for those with or without MYCN amplification now appear similar. Higher doses of chemotherapy may ameliorate the effect of MYCN amplification in patients with high-risk neuroblastoma.

Topics: Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Cisplatin; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Etoposide; Female; Gene Amplification; Genes, myc; Hematopoietic Stem Cell Transplantation; Humans; Infant; Japan; Life Tables; Male; Neuroblastoma; Prognosis; Prospective Studies; Remission Induction; Survival Rate; Transplantation Conditioning; Treatment Outcome

We have determined whether sequential molecular detection of minimal residual disease (MRD) in bone marrow (BM) could predict the outcome of patients with advanced neuroblastoma (NB).. Bone marrow samples from 19 patients over 12 months of age with stage 4 neuroblastoma were sequentially examined for tumor cell contamination by detecting tyrosine hydroxylase (TH) mRNA using reverse transcription-polymerase chain reaction (RT-PCR). All patients received repetitive multi-drug chemotherapy including cisplatin, cyclophosphamide or ifosphamide, adriamycin, and etoposide or vincristine. Seventeen patients received myeloablative therapy with hematopoietic stem cell transplantation after achieving complete remission.. All but one patient were histologically positive for tumor cells in BM samples at diagnosis, and they became negative for tumor cells within 3 months histologically. By the RT-PCR analysis, all patients were positive for TH mRNA in BM samples at diagnosis, and they became negative for TH mRNA 1 to 13 months after the start of chemotherapy. Six patients whose BM samples became negative for TH mRNA within 4 months after the start of chemotherapy remained alive without evidence of disease (median 61 months, range 20-76). In contrast, 12 of 13 patients whose BM samples remained positive at that time developed relapse and 10 of them died of disease (median 24 months, range 13-43). There was a statistically significant difference in survival between the two groups (P < 0.05). No significant difference of clinical characteristics by the MRD positivity at 4 months after the start of chemotherapy.. Persistence of MRD in BM at 4 months after the start of chemotherapy could predict poor prognosis in advanced neuroblastoma.

Topics: Adrenal Gland Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bone Marrow Examination; Bone Marrow Transplantation; Chemotherapy, Adjuvant; Child; Child, Preschool; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Etoposide; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Humans; Ifosfamide; Life Tables; Neoplasm Metastasis; Neoplasm Proteins; Neoplasm Staging; Neoplasm, Residual; Neuroblastoma; Prognosis; Retroperitoneal Neoplasms; RNA, Messenger; RNA, Neoplasm; Survival Analysis; Treatment Outcome; Tyrosine 3-Monooxygenase; Vincristine

Topics: Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Female; Humans; Infant; Leukemia-Lymphoma, Adult T-Cell; Neoplasms, Second Primary; Neuroblastoma

In the hospitals of the Tohoku Neuroblastoma Study Group (TNBSG), treatment for children with advanced neuroblastoma (NB) was intensified in the mid-1990's with the introduction of myeloablative therapy (MT) with stem cell transplantation (SCT) including the use of autologous peripheral blood stem cells (PBSC) and bone marrow transplantation (BMT). In this report, we examined whether the intensified therapy improved the outcome of children with advanced NB (age> 12 months) who were diagnosed between 1991 and 1997. Patients were 36 children (23 boys and 13 girls) with an average age of 3.4 years (range; 1 to 14 years). Six of them had stage III disease, and the other 30 had stage IV. They were treated initially with induction chemotherapy, surgery, and post-operative chemoradiotherapy, after which 17 of them continued further chemotherapy and the other 19 received MT/SCT (18 with PBSCT and 1 with BMT). Progression-free survival (PFS) rate at seven years from diagnosis was 43.5% for all patients, 66.7% for stage III patients and 38.2% for stage IV patients. The difference between stage III and IV patients was not significant. Among the 30 patients with stage IV disease, PFS at seven years was significantly higher in the 19 patients who received MT/SCT (55.6%) than in the 11 patients who did not receive it (12.5%). There was no difference in clinical and biological risk factors between these two groups, except for the proportion of patients with favorable response to initial therapy (36% and 80% for patients without and with MT/SCT, respectively). Furthermore, the proportion of patients with N-myc amplification was significantly higher in patients with progressive disease (PD) after MT/SCT than in those in CR after MT/SCT. The results of this retrospective study of children with advanced NB suggest that therapy intensification involving MT/SCT might result in lengthened survival time for patients with stage IV disease, and that post-transplant PD remains a risk for patients with high levels of N-myc amplification.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Child; Child, Preschool; Combined Modality Therapy; Doxorubicin; Etoposide; Hematopoietic Stem Cell Transplantation; Humans; Infant; Japan; Melphalan; Myeloablative Agonists; Neuroblastoma; Retrospective Studies; Risk Factors; Survival Rate; Transplantation Conditioning; Treatment Outcome; Universities

According to initial reports, stage 4 neuroblastoma patients with amplification of the MYCN proto-oncogene developed progressive disease within 8 months. The prognosis for such patients, however, should now be reevaluated in light of recent results achieved with up-to-date combination chemotherapy.. Patients with stage 3, 4, and 4S neuroblastoma and more than 10 copies of MYCN received induction chemotherapy, which from January 1985 to February 1991 consisted of regimen A(1 )(cyclophosphamide 1,200 mg/m(2) on day 1, vincristine 1.5 mg/m(2) on day 1, pirarubicin 40 mg/m(2) on day 3, and cisplatin 90 mg/m(2) on day 5) and from March 1991 to September 1993 consisted of regimen A(3 )(cyclophosphamide 1,200 mg/m(2) on days 1 and 2, pirarubicin 40 mg/m(2) on day 3, etoposide 100 mg/m(2) on days 1 through 5, and continuous infusion cisplatin 25 mg/m(2) on days 1 through 5). Most of these patients underwent radical surgery to remove the original tumor and local metastases, irradiation, and supralethal preconditioning regimens, followed by blood stem-cell transplantation (SCT). Data on the patients were collected in December 1998, and the factors contributing to disease-free survival were analyzed.. During the study period, 66 patients with more than 10 copies of MYCN were treated. Five of nine patients with stage 3 disease, 13 of 55 with stage 4, and one of two with stage 4S survived for at least 66 months. It is interesting that all but one patient who survived for more than 66 months underwent SCT, in contrast with only five of 45 patients who died.. Not all patients with advanced neuroblastoma who have more than 10 copies of MYCN will die. The requisites for survival in such patients seem to be intensive induction chemotherapy, effective surgery, irradiation, and the use of SCT.

Topics: Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Cisplatin; Cyclophosphamide; Disease-Free Survival; DNA, Neoplasm; Doxorubicin; Etoposide; Female; Follow-Up Studies; Humans; Infant; Male; Neuroblastoma; Prognosis; Proto-Oncogene Mas; Proto-Oncogene Proteins c-myc; Survivors; Vincristine

In January 1985, a single protocol consisting of cyclophosphamide, vincristine, tetrahydropyranyl adriamycin, and cis-platinum for the treatment of advanced neuroblastoma was begun nationwide in Japan and was found to improve clinical results significantly in terms of 2- or 3-year survival rate. Between January 1985 and December 1988, 113 eligible patients (7 infants younger than 12 months of age with stage IVA disease and 106 patients aged 12 months or older with stage III or IV disease) were enrolled and followed up for 5 years or more after initiation of treatment, as of March 1994. In this study, the usefulness of the protocol for the treatment of advanced neuroblastoma was evaluated with survival rates in relation to age, tumor site, stage, and N-myc amplification for patients surviving more than 5 years after initiation of the protocol. Fifty of the 113 patients were alive 5 years or more after initiation of the treatment, 39 without any episodes of disease recurrence. Fourteen (70%) of 20 patients with stage III, 6 (50%) of 12 with stage IVB, and 24 (30%) of 81 with stage IVA disease were alive and disease-free 5 years after initiation of the protocol. Twenty (56%) of 36 patients without N-myc amplification were alive at 5 years after initiation of the protocol. Only one patient who was alive without evidence of the disease at 5 years had recurrence afterward.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Child; Child, Preschool; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Female; Humans; Infant; Neuroblastoma; Survival Rate; Vincristine

A 35-year-old woman was admitted with complaints of severe posterior femoral pain and was diagnosed as having sacral neuroblastoma by tumor open biopsy. After admission, combination chemotherapy consisting of CDDP, etoposide, CPA, and THP was started intra-arterially and intravenously. After 2 courses of chemotherapy, her symptoms markedly improved and the tumor size was reduced. Now, after completion of 16 courses of chemotherapy, she is in a state of partial remission. Hereafter, we intend to reconsider the treatment strategy including surgical therapy.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Etoposide; Female; Humans; Neuroblastoma; Sacrum; Spinal Neoplasms

In 1985, a nationwide single protocol (cyclophosphamide, vincristine, tetrahydropyranyl Adriamycin, and cisplatin) for the treatment of advanced neuroblastoma was begun in Japan and was found to significantly increase the 3-year survival rate--to 70% for stage III, and to 45% for stage IV. In this study, the authors investigated the efficacy of this protocol for advanced neuroblastoma with or without N-myc amplification. In 159 of the 233 patients with advanced neuroblastoma treated with this protocol (between January 1985 and March 1993), genomic amplification of N-myc was determined. These 159 patients were divided into two groups according to the number of N-myc copies, ie, those with fewer than 10 copies (105 patients) and those with 10 or more copies (54 patients). The survival curves for the two groups were significantly different. The 5-year survival rate for patients with 10 or more copies was 43.9%; this is surprisingly high in comparison to results of previous studies in which no survivors were expected in cases of advanced neuroblastoma with highly amplified N-myc. Persistent bone marrow suppression was common, but there were no deaths attributable to drug side effects. Five patients with fewer than copies of N-myc amplification died more than 3 years after initial treatment. Three of the five had tumors with an unfavorable Shimada classification, and two had diploid nuclear DNA content. The authors conclude that the protocol resulted in dramatic improvement in the patients with advanced neuroblastoma, even with high N-myc amplification.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cisplatin; Cyclophosphamide; Doxorubicin; Gene Amplification; Genes, myc; Humans; Infant; Neuroblastoma; Survival Rate; Vincristine

For the purpose of studying clinical evaluation of A 1 protocol for advanced neuroblastoma, chemotherapy with vincristine, cyclophosphamide, THP-adriamycin and cisplatin was performed in 8 pediatric patients with advanced neuroblastoma undergoing second look operation (4) or delayed primary operation (4). Tumor volume measured on CT, histological finding of tumor obtained at operation, blood and urinary tumor marker level were studied.. 1) The chemotherapy is supposed to be effective for round cell type neuroblastoma. On the other hand, it is ineffective for composite type ganglioneuroblastoma. 2) More than 3 courses of A 1 protocol are necessary to yield a good effect. 3) There is no relationship between the effect of the chemotherapy and the prognosis.

Topics: Adrenal Gland Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Biopsy; Child; Child, Preschool; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Drug Evaluation; Female; Humans; Infant; Male; Neoplasm Staging; Neuroblastoma; Organoplatinum Compounds; Prognosis; Remission Induction; Reoperation; Vincristine

Ten patients in stages III or IV of neuroblastoma have been receiving treatment on the basis of a group study protocol that is supported by grant from the Ministry of Health and Welfare. Their chemotherapy regimen has consisted of a combination of cyclophosphamide, vincristine, THP-adriamycin, cisplatin, nimustine and dacarbazine. Surgery has been performed on all patients and in 7 patients their primary tumors were resected either as a delayed primary operation or a second look operation. Radiotherapy has been used for four patients at a total dose of 22-40 Gy. Six patients still survive (survival time: 5-27 months) with time spans that have ranged from 2-19 months of complete response. Major complications have been renal insufficiency, hearing loss, cardiac insufficiency, and bone marrow suppression, We focus mainly on the problems of this multidisciplinary treatment protocol.

Topics: Adrenal Gland Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Dacarbazine; Doxorubicin; Enteral Nutrition; Female; Humans; Infant; Male; Mediastinal Neoplasms; Neuroblastoma; Nimustine; Nitrosourea Compounds; Vincristine

Five patients with advanced neuroblastoma were treated with the protocol of the Welfare Ministry used by the Sawaguchi group. This protocol consists of cyclophosphamide (CPM), vincristine (VCR), 4'-O-tetrahydropyranyladriamycin (THP-ADM) and cisplatinum (CDDP). Two patients treated with this protocol as the first therapy obtained partial remission. Two patients who had obtained complete remission before the treatment with this protocol remained in complete remission after the treatment. One patient who had shown poor response to the therapy given before treatment with this protocol also showed poor response to the protocol. The most significant side effect with this protocol was myelosuppression, the severity of which was closely related to the dose of THP-ADM. Damage to the liver, kidney and heart was not very significant. We advocate that patients with advanced neuroblastoma can obtain complete remission with the aid of surgery and radiotherapy, etc., if they are treated with the present protocol as the first therapy.

Topics: Adrenal Gland Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Child, Preschool; Cisplatin; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Humans; Infant; Male; Neuroblastoma; Remission Induction; Vincristine