melphalan and Germinoma

To determine the response, toxicity, and survival for children with progressive or recurrent medulloblastoma and germinoma using a single myeloablative course of chemotherapy supported by autologous hematopoietic stem cells.. Subjects were in second remission or had minimal residual disease at the time of study entry. The conditioning regimen consisted of cyclophosphamide 6,000 mg/m(2) plus melphalan 180 mg/m(2).. Twenty-nine evaluable pediatric patients were accrued. The most frequent major toxicities were myelosuppression, infections, and stomatitis, but no toxic deaths were recorded. Best responses were: CR = 6, CCR = 13, PR = 6, SD = 2, and PD = 2. There were 6 medulloblastoma and 3 germinoma survivors with a median follow-up of 7.5 years (range = 2.8-10). Two germinoma survivors received radiotherapy after autografting for presumptive progressive disease.. Myeloablative chemotherapy consisting of cyclophosphamide and melphalan was tolerable in the relapsed brain tumor setting with 19/29 cases achieving CR or CCR status and 9/29 becoming long-term survivors.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Central Nervous System Neoplasms; Child; Child, Preschool; Cyclophosphamide; Germinoma; Hematopoietic Stem Cell Transplantation; Humans; Kaplan-Meier Estimate; Medulloblastoma; Melphalan; Neoplasm Recurrence, Local; Transplantation, Autologous

Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Central Nervous System Neoplasms; Chemoradiotherapy; Germinoma; Humans; Magnetic Resonance Imaging; Male; Melphalan; Salvage Therapy; Second-Look Surgery; Tumor Burden; Young Adult

Although (11)C-methionine (MET)-PET has been used to diagnose intracranial germ cell tumors (GCTs) arising in the basal ganglia, whether this imaging technique is useful in assessing treatment response and residual tumor is still unclear. The authors report 3 cases of basal ganglia GCTs in which the residual MET uptake at the end of treatment did not develop into a relapse, even without additional treatment. Case 1 is a 22-year-old man who had a second relapse of a left basal ganglia germinoma with diffuse dissemination on the walls of both of his lateral ventricles. MET-PET revealed high MET accumulation around tumors and their surroundings (maximum standardized uptake value [SUVmax] 3.3). After all treatments, MET-PET demonstrated mild tracer accumulation in both basal ganglia (SUVmax 2.2). Progression-free survival was 56 months from the second relapse without any further treatment. Case 2 is a 17-year-old boy with a left basal ganglia germinoma that showed increased MET uptake (SUVmax 4.2). After treatment, MET-PET revealed residual MET uptake (SUVmax 2.4) along the left posterior limb of the internal capsule. Progression-free survival was 52 months from the start of treatment. Case 3 is a 7-year-old boy with a left basal ganglia choriocarcinoma with increased tumor MET uptake (SUVmax 2.5). A minor enhanced mass remained on MRI after treatment with residual MET accumulation (SUVmax 1.4). Progression-free survival was 44 months. Treatment strategies based on MET uptake on PET should be carefully designed in patients with basal ganglia GCTs to avoid overtreatment and complications.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Basal Ganglia; Carbon Radioisotopes; Child; Choriocarcinoma; Combined Modality Therapy; Cranial Irradiation; Craniotomy; Cyclophosphamide; Disease-Free Survival; Etoposide; False Positive Reactions; Germinoma; Hematopoietic Stem Cell Transplantation; Humans; Ifosfamide; Lateral Ventricles; Male; Melphalan; Methionine; Neoplasm Recurrence, Local; Neoplasm, Residual; Organoplatinum Compounds; Positron-Emission Tomography; Radiopharmaceuticals; Radiotherapy, Adjuvant; Remission Induction; Supratentorial Neoplasms; Tissue Distribution; Young Adult

To determine the maximum-tolerated dose of cyclophosphamide (CTX) when administered sequentially with melphalan 60 mg/m2/d for 3 days, followed by autologous bone marrow rescue (ABMR), in children with recurrent or progressive malignant brain tumors, and to make preliminary observations on efficacy.. Nineteen patients between the ages of 2 and 21 years were enrolled and 18 were assessable for effects of therapy. CTX was administered to seven patients at 750 mg/m2/d for 4 days, to five patients at 975 mg/m2/d, to three patients at 1,200 mg/m2/d, and to three patients at 1,500 mg/m2/d. All patients received ABMR. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was used in 15 patients. Toxicity, response to therapy, time to progression, and survival and monitored.. The median time to a granulocyte count more than 500/dL was 19 days (range, 11 to 39), and for a platelet count more than 50,000/dL was 33 days (range, 16 to 60). Four heavily pretreated patients (22%) died of transplant-related complications. No dose-limiting, non-hematologic toxicities were defined for the study. Seven of 18 patients (39%) had a complete response (CR) or a partial response (PR). These included four patients with medulloblastoma (CR and three PRs), two with germinomas (two CRs), and one with ependymoma (one CR). The estimated 1-year survival rate was 39% (SE 12%).. CTX, at a maximum total dose of 6,000 mg/m2, administered sequentially with melphalan and followed by ABMR was tolerable in children with recurrent brain tumors who had not been heavily pretreated. Responses were seen in patients with medulloblastoma and germinomas. Further trials in children with chemosensitive tumors, with minimal residual disease, are planned.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Brain Neoplasms; Child; Child, Preschool; Combined Modality Therapy; Cyclophosphamide; Drug Administration Schedule; Ependymoma; Female; Germinoma; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Male; Medulloblastoma; Melphalan; Pilot Projects; Survival Rate; Transplantation, Autologous