Carboplatin in childhood brain tumors: A children's cancer study group phase II trial

Abstract

, Children's Cancer Study Group institutions entered 95 patients with recurrent brain tumors into a Phase I1 trial of carboplatin 560 mg/mz every 4 weeks. Complete or partial responses were observed for one of 19 evaluable children with brainstem glioma, two of 14 with ependymoma, six of 19 with medulloblastoma or central nervous system primitive neuroectodermal tumor (PNET), and none of 15 with high-grade astrocytoma. Of 33 children with medulloblastoma, ependymoma, or central nervous system PNET, five of 12 with no prior cisplatin exposure had responses, and two of 2 1 with prior cisplatin exposure had responses (P = 0.03). Thirty-four percent of patients had absolute neutrophil count nadirs less than 500/pl, and 37% had platelet count nadirs less than 25,000/ pl. Sixteen percent had moderate to severe otoxicity, 10% had nausea and vomiting, and none had nephrotoxicity. Cancer 662465-2469,1990.

Phase II study of oxaliplatin in children with recurrent or refractory medulloblastoma, supratentorial primitive neuroectodermal tumors, and atypical teratoid rhabdoid tumors

“…1,40 Several single agents and combination chemotherapy regimens have demonstrated activity in this group of patients. [2][3][4][7][8][9][10][11][12] Among the most active are platinum analogs. [7][8][9][10][11][12] Although the reported response rates in patients with recurrent MB with cisplatin and carboplatin are up to 40%, [7][8][9][10][11][12] comparison with the current cohort is very difficult, as many patients included in the earlier studies were chemonaive, because frontline therapy before the mid-1980s consisted of radiotherapy only.…”

“…[1][2][3][4][5][6] Both cisplatin [7][8][9] and carboplatin [10][11][12] have shown significant activity in this group of tumors, with cisplatin remaining the preferred agent by many neuro-oncologists. [13][14][15] However, cisplatin-associated ototoxicity and nephrotoxicity remain of great concern.…”

Phase II trial of carboplatin and etoposide for patients with recurrent high-grade glioma

“…Carboplatin is an alkylating agent widely used in the treatment of human tumours, and the synergistic effect when used together with etoposide has been proved either in vitro and in vivo. Carboplatin has exhibited activity against malignant glioma in vitro (Dodion et al, 1988), and it has been widely used to treat both paediatric (Gaynon et al, 1990;Friedman et al, 1992;Gururangan et al, 2002) and adult (Poisson et al, 1991;Twelves et al, 1991;Yung et al, 1991;Warnick et al, 1994) brain tumour patients.…”

Topotecan combined with myeloablative doses of thiotepa and carboplatin for neuroblastoma, brain tumors, and other poor-risk solid tumors in children and young adults

“…Reasons for treatment intensification in such patients using thiotepa, carboplatin, and topotecan included the steep dose-response antitumor effect of alkylators, 21,22 evidence that alkylators are non-crossresistant, 22 the enhancing effect of topotecan on alkylator cytotoxicity, 7 and the activity of each agent against a broad range of cancers, including brain tumors. [9][10][11][12][13][22][23][24][25][26][27][28][29][30][31] Toxicity was severe but manageable. Assessment of antitumor efficacy was limited by CR status at study entry of most patients, short follow-up, post-transplant use of biological therapies in neuroblastoma patients, and the small number of patients with other tumors.…”

“…The relapse-free results to date are consistent with the previously reported 23,25,28,29,38 efficacy of thiotepa and carboplatin against brain tumors and poor-prognosis germ cell tumors; the addition of topotecan may enhance efficacy. A beneficial role for this or any other myeloablative regimen in the treatment of metastatic sarcomas is uncertain.…”