A Phase I Clinical and Pharmacokinetic Study of Carboplatin and Autologous Bone Marrow Support

Abstract

The key to Fig 1 in the report by Shea et al published in the May issue (J Clin Oncol 7:651–661, 1989) contained several errors. It is reprinted here correctly with the figure in its entirety. Please see the PDF for Figure.

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

“…11,13,23,27,32 Preclinical studies support combined use of topotecan with alkylators. 7 However, when given with cyclophosphamide or cisplatin in conventional treatments, [33][34][35][36][37] topotecan has been dosed at 1 to 6 mg/m 2 -well below the singleagent maximally-tolerated dose of 10-12 mg/m 2 .…”

“…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.…”

A phase I dose escalation study of high-dose thiotepa, melphalan and carboplatin (TMCb) followed by autologous peripheral blood stem cell transplantation (PBSCT) in patients with solid tumors and hematologic malignancies

“…27 Carboplatin can be dose-escalated as a single agent to 2000 mg/m 2 when followed by autologous marrow or stem cell infusion resulting in a high response rate in patients with refractory ovarian carcinoma. 28 Carboplatin has also been used as a part of CTCb and ICE regimens for treatment of various solid tumors with HDC and autologous PBSCT. 3,[28][29][30][31] Calvert et al 47 have documented the importance of dosing by a calculated target formula which compensates for renal function, age and gender when conventional doses of carboplatin are administered.…”

“…28 Carboplatin has also been used as a part of CTCb and ICE regimens for treatment of various solid tumors with HDC and autologous PBSCT. 3,[28][29][30][31] Calvert et al 47 have documented the importance of dosing by a calculated target formula which compensates for renal function, age and gender when conventional doses of carboplatin are administered. It has been demonstrated that estimated AUC values of carboplatin in several studies overlapped with dosing on a mg/m 2 basis.…”

“…3 Carboplatin as a part of ICE (ifosfamide, carboplatin and etoposide) and CTCb (cyclophosphamide, thiotepa, carboplatin) HDC regimens has been used for the treatment of various solid tumors with autologous PBSCT. 3,[27][28][29][30][31] Based on these observations, we hypothesized that a HDC regimen of thiotepa, melphalan and carboplatin would have substantial antitumor activity. We report the results of a dose escalation study of carboplatin administered with a fixed dose of 500 mg/m 2 thiotepa and 100 mg/m 2 melphalan to determine the maximum tolerated dose (MTD) in patients with refractory malignancies.…”