TY - JOUR
T1 - Pharmacologic-guided trial of sequential methotrexate and thioguanine in children with advanced malignancies
AU - Tan, Charlotte T.C.
AU - Wollner, Norma
AU - Trippett, Tanya
AU - Goker, Erdem
AU - Tong, William P.Y.
AU - Kheradpour, Albert
AU - Meyers, Paul A.
AU - Vansyckle, Karen M.
AU - Guarino, Lee
AU - Elisseyeff, Yaroslav
AU - Bertino, Joseph R.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1994/9
Y1 - 1994/9
N2 - Purpose: Based on in vitro studies that have shown synergistic effects of sequential administration of methotrexate (MTX) and thioguanine (6-TG), we conducted a pharmacologically guided trial of sequential MTX and 6-TG to determine the following: (1) the maximum-tolerated dose (MTD) of 6-TG; (2) the nature of the dose-limiting toxicity; and (3) the modulation effect of MTX on 6-TG given by this sequence and schedule. Patients and Methods: Thirty-one children with advanced malignancies (acute leukemia, n = 10; lymphoma n = 10; and solid tumors, n = 11) were treated weekly for 3 weeks with a 2-week rest; treatment consisted of a fixed dose of MTX (30 mg/m2 over 24 hours) followed by a 2-hour infusion of 6-TG in escalating doses. Results: Measurement of plasma MTX, 6-TG, and mononuclear 5-phosphoribosyl- 1-pyrophosphate (PRPP) levels indicates that the desired biochemical modulation and serum levels were achieved. Nonhematologic toxicities were mild and the dose-limiting toxicity was bone marrow depression. A 300-mg/m2 dose of 6-TG with MTX is considered the MTD. Responses were noted in patients with lymphoma. Conclusion: Encouraging antitumor effects were produced with this regimen in heavily pretreated patients with lymphoma, particularly Hodgkin's disease (HD). The durations of responses were 17, 13+, 12, 9, and 7+ months. A phase II trial of the MTX/6-TG combination is warranted for the treatment of relapsed lymphoma.
AB - Purpose: Based on in vitro studies that have shown synergistic effects of sequential administration of methotrexate (MTX) and thioguanine (6-TG), we conducted a pharmacologically guided trial of sequential MTX and 6-TG to determine the following: (1) the maximum-tolerated dose (MTD) of 6-TG; (2) the nature of the dose-limiting toxicity; and (3) the modulation effect of MTX on 6-TG given by this sequence and schedule. Patients and Methods: Thirty-one children with advanced malignancies (acute leukemia, n = 10; lymphoma n = 10; and solid tumors, n = 11) were treated weekly for 3 weeks with a 2-week rest; treatment consisted of a fixed dose of MTX (30 mg/m2 over 24 hours) followed by a 2-hour infusion of 6-TG in escalating doses. Results: Measurement of plasma MTX, 6-TG, and mononuclear 5-phosphoribosyl- 1-pyrophosphate (PRPP) levels indicates that the desired biochemical modulation and serum levels were achieved. Nonhematologic toxicities were mild and the dose-limiting toxicity was bone marrow depression. A 300-mg/m2 dose of 6-TG with MTX is considered the MTD. Responses were noted in patients with lymphoma. Conclusion: Encouraging antitumor effects were produced with this regimen in heavily pretreated patients with lymphoma, particularly Hodgkin's disease (HD). The durations of responses were 17, 13+, 12, 9, and 7+ months. A phase II trial of the MTX/6-TG combination is warranted for the treatment of relapsed lymphoma.
UR - http://www.scopus.com/inward/record.url?scp=0028046851&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028046851&partnerID=8YFLogxK
U2 - 10.1200/JCO.1994.12.9.1955
DO - 10.1200/JCO.1994.12.9.1955
M3 - Article
C2 - 7521908
AN - SCOPUS:0028046851
SN - 0732-183X
VL - 12
SP - 1955
EP - 1962
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 9
ER -