mesna and Neuroectodermal-Tumors--Primitive

We have evaluated the response rate and survival utilizing intensified chemotherapy followed by myeloablative chemotherapy with autologous hematopoietic cell rescue (AuHCR) and adjuvant radiation therapy in six young children with newly diagnosed brainstem primitive neuroectodermal tumors (bstPNET). Following maximum surgical resection of the tumor, patients received high dose induction chemotherapy including vincristine, cisplatin, cyclophosphamide, and etoposide. Eligible patients received a single cycle of myeloablative chemotherapy followed by AuHCR. Two patients survive at least 32 months with stable disease. This approach provides an alternative for young patients with bstPNET who in prior reports have had a uniformly fatal prognosis.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Brain Damage, Chronic; Brain Stem; Carboplatin; Child; Child, Preschool; Cisplatin; Combined Modality Therapy; Cranial Irradiation; Cyclophosphamide; Etoposide; Humans; Infant; Infratentorial Neoplasms; Leucovorin; Mesna; Methotrexate; Neuroectodermal Tumors, Primitive; Peripheral Blood Stem Cell Transplantation; Remission Induction; Thiotepa; Transplantation, Autologous; Vincristine

Children with newly diagnosed supratentorial primitive neuroectodermal tumors (sPNET) have poor outcomes compared to medulloblastoma patients, despite similar treatments. In an effort to improve overall survival (OS) and event-free survival (EFS) and to decrease radiation exposure, the Head Start (HS) protocols treated children with newly diagnosed sPNET utilizing intensified induction chemotherapy (ICHT) followed by consolidation with myeloablative chemotherapy and autologous hematopoietic cell rescue (AuHCR).. Between 1991 and 2002, 43 children with sPNET were prospectively treated on two serial studies (HS I and II). After maximal safe surgical resection, patients on HS I and patients with localized disease on HS II were treated with five cycles of ICHT (vincristine, cisplatin, cyclophosphamide, and etoposide). Patients on HS II with disseminated disease received high-dose methotrexate during ICHT. If the disease remained stable or in response, patients received a single cycle of high-dose myeloablative chemotherapy followed by AuHCR.. Five-year EFS and OS were 39% (95%CI: 24%, 53%) and 49 (95%CI: 33%, 62%), respectively. Non-pineal sPNET patients faired significantly better than those patients with pineal sPNETs. Metastasis at diagnosis, age, and extent of resection were not significant prognostic factors. Sixty percent of survivors (12 of 20) are alive without exposure to radiation therapy.. ICHT followed by AuHCR in young patients with newly diagnosed sPNET appears to not only provide an improved EFS and OS for patients who typically have a poor prognosis, but also it successfully permitted deferral and elimination of radiation therapy in a significant proportion of patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Child, Preschool; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Disease-Free Survival; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Male; Mesna; Methotrexate; Neuroectodermal Tumors, Primitive; Supratentorial Neoplasms; Survival Rate; Vincristine

Both 2-mercaptoethane sulfonate sodium (mesna) and amifostine's active metabolite WR-1065 are thiol-based cytoprotective agents that are critical components of high-dose chemotherapy regimens used to treat various cancers in both adults and children. This case report describes a patient with a supratentorial primitive neuroectodermal tumor who developed severe drug reactions to both mesna and amifostine/WR-1065, suggesting that the thiol component of these agents triggered the adverse reactions. This report highlights the clinical presentation of drug-induced hypersensitivity syndrome in the context of pediatric oncology and the supportive care measures that, if implemented rapidly, may diminish the reaction severity and allow successful completion of chemotherapy.

Topics: Amifostine; Antineoplastic Combined Chemotherapy Protocols; Child; Combined Modality Therapy; Cranial Irradiation; Drug Hypersensitivity; Humans; Male; Mesna; Neuroectodermal Tumors, Primitive; Prognosis; Protective Agents; Sulfhydryl Compounds; Supratentorial Neoplasms

The role of tandem high-dose chemotherapy (HDC) with autologous peripheral hematopoietic progenitor cell rescue (APHPCR) in patients with Ewing Family Tumors (EFT) is controversial. We initiated treatment for eight consecutive patients with high-risk EFT with HDC and APHPCR from 1992 to 2003. There were no treatment related deaths. Four patients remain in complete remission, including three who did not undergo local therapy to bone at either the primary or metastatic sites. Our experience has shown that treatment of EFT patients with tandem HDC with APHPCR may benefit a subgroup of high-risk patients in whom optimal local therapy is not possible.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Child; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Etoposide; Feasibility Studies; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Neoadjuvant Therapy; Neuroectodermal Tumors, Primitive; Pelvic Bones; Peripheral Blood Stem Cell Transplantation; Remission Induction; Risk; Sarcoma, Ewing; Scapula; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Vincristine

Ewing's sarcoma and primitive neuroectodermal tumour (ES/PNET) are rare, limiting opportunities for therapy studies in adults. Chemotherapy regimens adapted from paediatric studies are often used for adults but concerns about poor outcome and treatment toxicity may adversely affect drug dose intensity. We present our experience using a paediatric protocol at full dose.. Records of 34 patients with ES/PNET who received the IVAD chemotherapy regimens were reviewed. Received drug dose intensity, toxicity and survival data were collected.. Received dose intensity in 30 evaluable patients was 0.92 compared to the standard IVAD schedule. Myelosuppression was the major toxicity, 83% of patients experienced grade 4 neutropenia. There was no major renal or cardiac toxicity. In patients without metastases at presentation, five-year overall survival was 63% and progression free survival was 39%. Tumour burden at presentation was statistically significantly associated with survival (P = 0.002). The five-year survival rate of 80% in patients presenting with low volume non metastatic disease was equivalent to published paediatric series.. Although the IVAD chemotherapy regimens are myelotoxic in adults, they can be given safely. We recommend that adults with ES/PNET should be included in current multicentre, multidisciplinary treatment studies directed at children.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Brain Neoplasms; Cyclophosphamide; Disease-Free Survival; Dose-Response Relationship, Drug; Doxorubicin; Drug Administration Schedule; Etoposide; Feasibility Studies; Female; Humans; Ifosfamide; Infusions, Intravenous; Injections, Intravenous; Male; Mesna; Middle Aged; Neuroectodermal Tumors, Primitive; Neutropenia; Sarcoma, Ewing; Vincristine