Phase I study of BCNU and intravenous 6-mercaptopurine in patients with anaplastic gliomas

David C. Smith; Nicholas A. Vick; Donald L. Trump; Henry S. Friedman; Allan H. Friedman; Joseph Purvis; Al Gauspari; S. Clifford Schold

doi:10.1007/BF00686294

Phase I study of BCNU and intravenous 6-mercaptopurine in patients with anaplastic gliomas

David C. Smith, Nicholas A. Vick, Donald L. Trump, Henry S. Friedman, Allan H. Friedman, Joseph Purvis, Al Gauspari, S. Clifford Schold

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Abstract

On the basis of response rates of up to 50%, BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea] is the primary drug used in the chemotherapy of anaplastic gliomas. Preclinical data obtained in several experimental systems show that the cytotoxicity of chloroethylnitrosoureas can be increased by the concomitant use of thiopurines. In this phase I trial, patients with anaplastic gliomas received standard-dose BCNU (200 mg/m²×1) in combination with escalating doses of intravenous 6-mercaptopurine (200, 350, 500, and 750 mg/m² daily×3), with BCNU being given on day 3 to maximize the effect of the drugs on cellular DNA. No increase in hematologic toxicity was demonstrated as the dose of 6-mercaptopurine was increased. Responses and stabilization of disease were observed in several patients. Due to the safety of and the evidence of activity found for this regimen in the present trial, 750 mg/m² 6-mercaptopurine has been incorporated into subsequent studies.

Original language	English
Pages (from-to)	272-276
Number of pages	5
Journal	Cancer Chemotherapy and Pharmacology
Volume	30
Issue number	4
DOIs	https://doi.org/10.1007/BF00686294
State	Published - Jul 1992
Externally published	Yes

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title = "Phase I study of BCNU and intravenous 6-mercaptopurine in patients with anaplastic gliomas",

abstract = "On the basis of response rates of up to 50%, BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea] is the primary drug used in the chemotherapy of anaplastic gliomas. Preclinical data obtained in several experimental systems show that the cytotoxicity of chloroethylnitrosoureas can be increased by the concomitant use of thiopurines. In this phase I trial, patients with anaplastic gliomas received standard-dose BCNU (200 mg/m2×1) in combination with escalating doses of intravenous 6-mercaptopurine (200, 350, 500, and 750 mg/m2 daily×3), with BCNU being given on day 3 to maximize the effect of the drugs on cellular DNA. No increase in hematologic toxicity was demonstrated as the dose of 6-mercaptopurine was increased. Responses and stabilization of disease were observed in several patients. Due to the safety of and the evidence of activity found for this regimen in the present trial, 750 mg/m2 6-mercaptopurine has been incorporated into subsequent studies.",

author = "Smith, {David C.} and Vick, {Nicholas A.} and Trump, {Donald L.} and Friedman, {Henry S.} and Friedman, {Allan H.} and Joseph Purvis and Al Gauspari and Schold, {S. Clifford}",

year = "1992",

month = jul,

doi = "10.1007/BF00686294",

language = "English",

volume = "30",

pages = "272--276",

journal = "Cancer Chemotherapy and Pharmacology",

issn = "0344-5704",

publisher = "Springer Verlag",

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T1 - Phase I study of BCNU and intravenous 6-mercaptopurine in patients with anaplastic gliomas

AU - Smith, David C.

AU - Vick, Nicholas A.

AU - Trump, Donald L.

AU - Friedman, Henry S.

AU - Friedman, Allan H.

AU - Purvis, Joseph

AU - Gauspari, Al

AU - Schold, S. Clifford

PY - 1992/7

Y1 - 1992/7

N2 - On the basis of response rates of up to 50%, BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea] is the primary drug used in the chemotherapy of anaplastic gliomas. Preclinical data obtained in several experimental systems show that the cytotoxicity of chloroethylnitrosoureas can be increased by the concomitant use of thiopurines. In this phase I trial, patients with anaplastic gliomas received standard-dose BCNU (200 mg/m2×1) in combination with escalating doses of intravenous 6-mercaptopurine (200, 350, 500, and 750 mg/m2 daily×3), with BCNU being given on day 3 to maximize the effect of the drugs on cellular DNA. No increase in hematologic toxicity was demonstrated as the dose of 6-mercaptopurine was increased. Responses and stabilization of disease were observed in several patients. Due to the safety of and the evidence of activity found for this regimen in the present trial, 750 mg/m2 6-mercaptopurine has been incorporated into subsequent studies.

AB - On the basis of response rates of up to 50%, BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea] is the primary drug used in the chemotherapy of anaplastic gliomas. Preclinical data obtained in several experimental systems show that the cytotoxicity of chloroethylnitrosoureas can be increased by the concomitant use of thiopurines. In this phase I trial, patients with anaplastic gliomas received standard-dose BCNU (200 mg/m2×1) in combination with escalating doses of intravenous 6-mercaptopurine (200, 350, 500, and 750 mg/m2 daily×3), with BCNU being given on day 3 to maximize the effect of the drugs on cellular DNA. No increase in hematologic toxicity was demonstrated as the dose of 6-mercaptopurine was increased. Responses and stabilization of disease were observed in several patients. Due to the safety of and the evidence of activity found for this regimen in the present trial, 750 mg/m2 6-mercaptopurine has been incorporated into subsequent studies.

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VL - 30

SP - 272

EP - 276

JO - Cancer Chemotherapy and Pharmacology

JF - Cancer Chemotherapy and Pharmacology

IS - 4

ER -

Phase I study of BCNU and intravenous 6-mercaptopurine in patients with anaplastic gliomas

Abstract

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