High-dose chemotherapy with autologous stem-cell rescue in patients with recurrent and high-risk pediatric brain tumors. Malignant ovarian germ cell tumors: the experience at the Hospital de la Santa Creu i Sant Pau.
We treated 49 patients with recurrent or poor-prognosis CNS malignancies with high-dose chemotherapy regimens followed by autologous marrow rescue with or without peripheral-blood stem-cell augmentation to determine the toxicity of and event-free survival after these regimens.
                Nineteen patients had medulloblastomas, 12 had glial tumors, seven had pineoblastomas, five had ependymomas, three had primitive neuroectodermal tumors, two had germ cell tumors, and one had fibrosarcoma. Thirty-seven received chemotherapy with cyclophosphamide 1.5 g/m2 daily x 4 and melphalan 25 to 60 mg/m2 daily x 3. Nine received busulfan 37.5 mg/m2 every 6 hours x 16 and melphalan 180 mg/m2 (n = 7) or 140 mg/m2 (n = 2). Three received carboplatin 700 mg/m2/d on days -7, -5, and -3 and etoposide 500 mg/m2/d on days -6, -4, and -2. All patients received standard supportive care.
                Eighteen of 49 patients survive event-free 22+ to 55+ months (median, 33+) after transplantation, including nine of 16 treated before recurrence and nine of 33 treated after recurrence. There was one transplant-related death from pulmonary aspergillosis. Of five patients assessable for disease response, one had a partial remission (2 months), one has had stable disease (55+ months), and three showed progression 2, 5, and 8 months after transplantation.
                The toxicity of these regimens was tolerable. Certain patients with high-risk CNS malignancies may benefit from such a treatment approach. Subsequent trials should attempt to determine which patients are most likely to benefit from high-dose chemotherapy with autologous stem-cell rescue. From 1979 to 1990, 33 patients with pathologically confirmed malignant ovarian germ cell tumors (MOGCT) were referred after initial surgical procedure at the Department of Oncology, Hospital de la Santa Creu i Sant Pau. The median age was 22 years (range, 10 to 39). Stage distribution was as follows: stage I, 12 patients; stage II, 6 patients; stage III, 11 patients; stage IV, 3 patients; and unstaged, 1 patient. The histologic diagnoses were 10 dysgerminomas, 4 endodermal sinus tumors, 11 immature teratomas, and 8 mixed germ cell tumors. Twenty-eight out of the thirty-three patients received postoperative chemotherapy with POMB-ACE-PAV or other platinum-containing regimens. One patient with stage IV disease failed to respond to chemotherapy and she died. Sixteen out of the twenty-eight treated patients had second-look laparotomy, which showed mature teratoma in six and persistent malignant teratoma in one patient. This last patient had complete remission with second regimen. No patient has developed recurrence. With a median follow-up of 66 months (range, 10 to 133), 32 patients (97%) are alive without evidence of disease. These data confirm that platinum-containing regimens have dramatically improved the prognosis for patients with MOGCT. This paper discusses primary chemotherapy and the role of the second-look in these patients.
We found only low quality evidence on the use of chemotherapy in malignant germ cell tumours of the ovaries. Therefore we are unable to reach definite conclusions about the relative benefits and harms of chemotherapy use in this disease regardless of disease stage. Due to the benefit of chemotherapy in germ cell cancer of the testis, a trial of chemotherapy versus best supportive care is unlikely to be feasible. Despite this, good quality randomised studies are warranted in this disease to define the role of chemotherapy (type of chemotherapy, duration of treatment, benefit, short and long term toxicities). Given the rarity of this disease, we feel a trans-global approach would be essential in order to perform such trials.