TY - JOUR
T1 - A phase I/II study of high-dose cyclophosphamide, cisplatin, and thioTEPA followed by autologous bone marrow and granulocyte colony-stimulating factor-primed peripheral-blood progenitor cells in patients with advanced malignancies
AU - Hussein, Atif M.
AU - Petros, William P.
AU - Ross, Maureen
AU - Vredenburgh, James J.
AU - Affronti, Mary Lou
AU - Jones, Roy B.
AU - Shpall, Elizabeth J.
AU - Rubin, Peter
AU - Elkordy, Maha
AU - Gilbert, Colleen
AU - Gupton, Caroline
AU - Egorin, Merrill J.
AU - Soper, John
AU - Berchuck, Andrew
AU - Clarke-Pearson, Daniel
AU - Berry, Donald A.
AU - Peters, William P.
PY - 1996
Y1 - 1996
N2 - The purpose of the present study was to determine the maximally tolerated dose of thioTEPA given with fixed high-dose cyclophosphamide (CPA) and cisplatin (cDDP) followed by autologous bone marrow (ABM) with or without granulocyte colony-stimulating factor (G-CSF)-primed peripheral-blood progenitor cells (PBPCs) in patients with advanced malignancies. Patients were required to have histologically documented malignancies and adequate renal, hepatic, pulmonary, and cardiac function. CPA was given at 1,875 mg/m2 per day as a 1-h i.v. infusion for 3 consecutive days, and cDDP was given at 55 mg/m2 per day as a 24-h continuous i.v. infusion over 3 days concurrently with CPA. ThioTEPA was given once as a 1-h i.v. infusion (300-900 mg/m2) either following (the first 13 patients) or prior to CPA and cDDP. In all, 31 patients received PBPCs. A total of 46 patients were treated. There were 6 deaths among the 15 patients who did not receive PBPCs (13 received thioTEPA following CPA and cDDP). Among the other 31 patients who received PBPCs (all of whom also received thioTEPA prior to CPA and cDDP), there were 4 deaths, all involving patients with refractory ovarian carcinoma. The main toxicities were mucositis, esophagitis, hepatotoxicity, and nephrotoxicity. The median time required to achieve an absolute neutrophil count of 500 μl was 10 days (range, 9-12 days) for those who received PBPCs and 15 days (range, 15-34 days) for those who did not receive PBPCs. Altogether, 47% of the major organ toxicities (grades 3 and 4 renal, hepatic, and cardiac toxicities) occurred among the 15 patients who did not receive PBPCs, although these patients received thioTEPA at the lowest 2 dose levels. There were 3 complete responses and 22 partial responses among 35 evaluable patients (overall response rate, 71%), with the median duration of response being 3.5 months (range, 2-17 months). The maximally tolerated dose of thioTEPA was 600 mg/m2 given as a 1-h i.v. infusion on the day prior to CPA and cDDP administration. The combination of high-dose CPA, cDDP, and thioTEPA is a well-tolerated regimen when thioTEPA is given prior to CPA and cDDP and when the combination also includes PBPCs in addition to ABM. This regimen is active in a variety of malignancies.
AB - The purpose of the present study was to determine the maximally tolerated dose of thioTEPA given with fixed high-dose cyclophosphamide (CPA) and cisplatin (cDDP) followed by autologous bone marrow (ABM) with or without granulocyte colony-stimulating factor (G-CSF)-primed peripheral-blood progenitor cells (PBPCs) in patients with advanced malignancies. Patients were required to have histologically documented malignancies and adequate renal, hepatic, pulmonary, and cardiac function. CPA was given at 1,875 mg/m2 per day as a 1-h i.v. infusion for 3 consecutive days, and cDDP was given at 55 mg/m2 per day as a 24-h continuous i.v. infusion over 3 days concurrently with CPA. ThioTEPA was given once as a 1-h i.v. infusion (300-900 mg/m2) either following (the first 13 patients) or prior to CPA and cDDP. In all, 31 patients received PBPCs. A total of 46 patients were treated. There were 6 deaths among the 15 patients who did not receive PBPCs (13 received thioTEPA following CPA and cDDP). Among the other 31 patients who received PBPCs (all of whom also received thioTEPA prior to CPA and cDDP), there were 4 deaths, all involving patients with refractory ovarian carcinoma. The main toxicities were mucositis, esophagitis, hepatotoxicity, and nephrotoxicity. The median time required to achieve an absolute neutrophil count of 500 μl was 10 days (range, 9-12 days) for those who received PBPCs and 15 days (range, 15-34 days) for those who did not receive PBPCs. Altogether, 47% of the major organ toxicities (grades 3 and 4 renal, hepatic, and cardiac toxicities) occurred among the 15 patients who did not receive PBPCs, although these patients received thioTEPA at the lowest 2 dose levels. There were 3 complete responses and 22 partial responses among 35 evaluable patients (overall response rate, 71%), with the median duration of response being 3.5 months (range, 2-17 months). The maximally tolerated dose of thioTEPA was 600 mg/m2 given as a 1-h i.v. infusion on the day prior to CPA and cDDP administration. The combination of high-dose CPA, cDDP, and thioTEPA is a well-tolerated regimen when thioTEPA is given prior to CPA and cDDP and when the combination also includes PBPCs in addition to ABM. This regimen is active in a variety of malignancies.
KW - Bone marrow transplantation
KW - Chemotherapy
KW - Phase I/II trial
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UR - http://www.scopus.com/inward/citedby.url?scp=0029874346&partnerID=8YFLogxK
U2 - 10.1007/s002800050429
DO - 10.1007/s002800050429
M3 - Article
C2 - 8612310
AN - SCOPUS:0029874346
SN - 0344-5704
VL - 37
SP - 561
EP - 568
JO - Cancer chemotherapy and pharmacology
JF - Cancer chemotherapy and pharmacology
IS - 6
ER -