mesna and Neuroblastoma

Topotecan is an active drug in relapsed neuroblastoma. We investigated the efficacy and toxicity of a topotecan-based induction regimen in newly diagnosed neuroblastoma.. Patients older than 1 year with either metastatic or localised stage 2-3 MYCN-amplified neuroblastoma received 2 courses of high-dose topotecan (HD-TPT) 6mg/m(2) and high-dose cyclophosphamide (HD-CPM) 140 mg/kg, followed by 2 courses of ifosfamide, carboplatin and etoposide (ICE) every 28 days. After surgery on primary tumour, a fifth course with vincristine, doxorubicin and CPM was given, followed by high-dose chemotherapy with stem cell support. Response was assessed in accordance with the International Neuroblastoma Response Criteria.. Of 35 consecutive patients, 33 had metastatic disease. The median length of induction phase was 133 days (range 91-207) and time to high-dose chemotherapy was 208 days (range 156-285). The median tumour volume reduction was 55% after two HD-TPT/HD-CPM courses and 80% after four courses. Radical surgery was performed in 16/27 patients after chemotherapy. After the fifth course, 29/34 patients (85%) had achieved a partial remission (12) or a CR/very good partial remission (17). CR of metastases was achieved in 13/32 (41%) and bone marrow was in complete remission in 16/24 patients (67%). Grade 4 neutropenia and/or thrombocytopenia occurred in 100% of HD-TPT/HD-CPM and in 95% of ICE courses, while non-haematological toxicities were manageable.. These data indicate that our induction regimen is feasible and well tolerated. A major response rate of 85% with 41% complete metastatic response confirms this regimen as effective induction in high-risk neuroblastoma.

Topics: Abdominal Neoplasms; Adolescent; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Child; Child, Preschool; Etoposide; Female; Humans; Ifosfamide; Infant; Kaplan-Meier Estimate; Lomustine; Male; Melphalan; Mesna; Neuroblastoma; Pilot Projects; Risk Factors; Thoracic Neoplasms; Topotecan; Treatment Outcome

Ifosfamide-induced nephrotoxicity is a serious adverse effect in children undergoing chemotherapy. Our previous cell and rodent models have shown that the antioxidant N-acetylcysteine (NAC), used extensively as an antidote for acetaminophen poisoning, protects renal tubular cells from ifosfamide-induced nephrotoxicity at a clinically relevant concentration. For the use of NAC to be clinically relevant in preventing ifosfamide nephrotoxicity, we must ensure there is no effect of NAC on the antitumor activity of ifosfamide. Common pediatric tumors that are sensitive to ifosfamide, human neuroblastoma SK-N-BE(2) and rhabdomyosarcoma RD114-B cells, received either no pretreatment or pretreatment with 400 µmol/L of NAC, followed by concurrent treatment with NAC and either ifosfamide or the active agent ifosfamide mustard. Ifosfamide mustard significantly decreased the growth of both cancer cell lines in a dose-dependent manner (p < 0.001). The different combined treatments of NAC alone, sodium 2-mercaptoethanesulfonate alone, or NAC plus sodium 2-mercaptoethanesulfonate did not significantly interfere with the tumor cytotoxic effect of ifosfamide mustard. These observations suggest that NAC may improve the risk/benefit ratio of ifosfamide by decreasing ifosfamide-induced nephrotoxicity without interfering with its antitumor effect in cancer cells clinically treated with ifosfamide.

Topics: Acetylcysteine; Antineoplastic Agents, Alkylating; Cell Line, Tumor; Cell Survival; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Humans; Ifosfamide; Mesna; Neuroblastoma; Phosphoramide Mustards; Rhabdomyosarcoma

Neuroblastoma is the most common extracranial solid malignancy in children but rarely described in adults, being 10% of all cases diagnosed after the first decade of life. We report a 23 year-old black woman with a mass at paravertebral region of T3-T5, multiple lesions in vertebral bodies and expanding skull-brain lesion at the right parietal region. Immunohistochemical analysis (negative for CD99, CD20, CD3 and desmin; and positive chromogranin, synaptophysin and NB84) confi rmed the diagnosis of neuroblastoma. The patient was submitted to 12 cycles of chemotherapy receiving VAC (vincristine/doxorubicin/cyclophosphamide) interspersed with ICE (ifosfamide/mesna/etoposide) and doxorubicin was replaced by actinomycin in the 7th cycle. She had good tolerance to this therapy, and has been clinically stable.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biopsy; Bone Neoplasms; Brain Neoplasms; Carboplatin; Cyclophosphamide; Doxorubicin; Etoposide; Female; Humans; Ifosfamide; Mesna; Neuroblastoma; Spinal Cord Compression; Spinal Cord Neoplasms; Thoracic Vertebrae; Vincristine; Young Adult

Focal nodular hyperplasia (FNH) is a benign, poorly understood hepatic tumor that is rare in children. Although there is no evidence for malignant degeneration, FNH can occur adjacent to a malignancy. Here, the case of a 4-year-old boy with a hepatic mass and history of stage IV neuroblastoma is presented. Initial imaging and core-needle biopsy were consistent with FNH. However, after left lateral segmentectomy, pathologic examination revealed a malignant tumor most consistent with small cell undifferentiated hepatoblastoma as well as 3 foci of FNH in the surrounding parenchyma.

Topics: Adrenal Gland Neoplasms; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carboplatin; Child, Preschool; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Etoposide; Fluorouracil; Focal Nodular Hyperplasia; Granulocyte Colony-Stimulating Factor; Hepatectomy; Hepatoblastoma; Humans; Ifosfamide; Immunoglobulin G; Incidental Findings; Liver Neoplasms; Male; Melphalan; Mesna; Neoplasms, Radiation-Induced; Neoplasms, Second Primary; Neuroblastoma; Radiotherapy, Adjuvant; Tomography, X-Ray Computed; Vincristine

We used high-dose cyclophosphamide plus topotecan/vincristine (CTV) or irinotecan (C/I) in patients with resistant neuroblastoma. The aim was to use a regimen with little risk to major organs to (a) achieve or consolidate remission in heavily treated patients and to (b) induce an immunological state conducive to passive immunotherapy with the murine 3F8 antibody.. CTV and C/I included cyclophosphamide 140 mg/kg ( approximately 4200 mg/m(2)). With CTV, topotecan 2 mg/m(2) was infused i.v. (30 min) on days 1-4 (total, 8 mg/m(2)), and vincristine 0.067 mg/kg was injected on day 1. With C/I, irinotecan, 50 mg/m(2) was infused i.v. (1 h) on days 1-5 (total, 250 mg/m(2)). Mesna and granulocyte colony-stimulating factor were used.. Twenty-nine patients received 38 courses of CTV, and 26 patients received 38 courses of C/I. All patients had previously received topotecan, a hemopoietic stem-cell transplant, and/or high-dose cyclophosphamide. CTV and C/I caused myelosuppression of comparably prolonged duration as follows: absolute neutrophil counts <500/ micro l lasted 5-12 days in patients who had not previously received transplant and 7-21 days in patients who were post-transplant. Other significant toxicities included typhlitis (two CTV-treated patients, one C/I-treated patient) and hemorrhagic cystitis (one C/I-treated patient). Major responses were seen in 4 (15%) of 26 CTV and 4 (17%) of 24 C/I-treated patients with assessable disease. Bone marrow disease resolved in 5 (28%) of 18 CTV-treated patients and in 4 (27%) of 15 C/I-treated patients. 3F8 after CTV or C/I was not blocked by neutralizing antibodies, consistent with the desired immunosuppressive effect of high-dose cyclophosphamide.. CTV and C/I require transfusional and antibiotic support but otherwise entail tolerable morbidity. They have modest antineuroblastoma activity in heavily treated patients and are good preparative regimens for passive immunotherapy with monoclonal antibodies.

Topics: Adolescent; Animals; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Child; Child, Preschool; Combined Modality Therapy; Cyclophosphamide; Drug Resistance, Neoplasm; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Immunotherapy; Infant; Irinotecan; Male; Mesna; Neuroblastoma; Retrospective Studies; Topotecan

The objective of this study was to determine the tolerance and toxicities of high-dose cyclophosphamide (CPA) at 7 g/m2 given in four fractions over 8 h in children with advanced solid tumors.. Twenty children aged 1 1/2-19 years (median, 12 years) received 24 courses of high-dose CPA at 7 g/m2 for the treatment of advanced malignant solid tumor. CPA was given in four 1-h infusions of 1.75 g/m2 each, with 1 h of rest between each dose. MESNA was used as a uroprotective agent and was continued for 24 h after the final dose of CPA. With only one exception, all patients were discharged at the end of MESNA infusion and received granulocyte colony-stimulating factor, prophylactic ciprofloxacin, and co-trimoxazole.. Severe but transient myelosuppression was observed. The median time to neutrophil and platelet recovery was 17 and 19 days, respectively. Fever developed after 13 of the 24 courses, and hospitalization was required. Extramedullary toxicities were mild. No patient showed cardiomyopathy or hemorrhagic cystitis. Forty-six percent of the courses were managed entirely on an outpatient basis. Objective tumor response was seen in five patients.. CPA at 7 g/m2 is well tolerated by children with advanced malignancies and should be considered in earlier phases of antineoplastic therapy.

Topics: Adolescent; Antineoplastic Agents, Alkylating; Child; Child, Preschool; Cyclophosphamide; Drug Administration Schedule; Feasibility Studies; Female; Granulocyte Colony-Stimulating Factor; Humans; Infant; Male; Mesna; Neoplasms; Neuroblastoma; Osteosarcoma; Sarcoma; Sarcoma, Ewing; Treatment Outcome

We studied the efficacy of mesna as a protectant for urotoxicity in pediatric patients receiving chemotherapy including oxazaphosphorines. Nineteen patients with malignant diseases (5 neuroblastoma, 3 acute lymphocytic leukemia, 4 acute non-lymphocytic leukemia, 2 non-Hodgkin lymphoma, 3 osteosarcoma and 2 rhabdomyosarcoma) were treated with a total of 106 courses of therapy between June of 1986 and May of 1989. Of these, no gross hematuria were seen. Microhematuria transiently occurred only in 2 courses (5%) of 1 patient (2%). These data indicated that mesna was highly effective for urotoxicity of oxazaphosphorines without any side effects, especially in pediatric patients.

Topics: Bone Neoplasms; Child; Cyclophosphamide; Cystitis; Female; Hematuria; Humans; Ifosfamide; Leukemia; Lymphoma, Non-Hodgkin; Male; Mercaptoethanol; Mesna; Neuroblastoma; Osteosarcoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Rhabdomyosarcoma