Literature DB >> 8094003

2'-Chlorodeoxyadenosine: evaluation of a novel predominantly lymphocyte selective agent in lymphoid malignancies.

T Hickish1, P Serafinowski, D Cunningham, A Oza, E Dorland, I Judson, B C Millar, T A Lister, A Roldan.   

Abstract

2'-Chlorodeoxyadenosine (2CDA) is a purine analogue selectively active against both resting and dividing lymphoid cells. Twenty-one patients with a variety of previously treated lymphoid malignancies received a total of 41 courses of 2CDA (0.1-0.15 mg/kg/day over 7 days continuous intravenous infusion) on compassionate grounds. The profile of the patient population was as follows: low grade non-Hodgkin's lymphoma (NHL) = 8, intermediate grade NHL = 2, transformed (intermediate grade NHL) = 6, Hodgkin's disease = 1, lymphoplasmacytoid NHL = 3 and lymphoblastic NHL = 1. The overall response rate was 53%, with three patients attaining complete remission (CR) and eight partial remission (PR). Three of 16 patients with primary resistant or resistant recurrent disease entered either CR (1) or PR (2). Ten patients had no response or progressive disease. The latter group was comprised of patients who had extensively pre-treated lymphoplasmacytoid tumours and/or poor performance status (WHO grades 2-4). The median duration of response is 6 months (range 1 to 12 months). Treatment was well tolerated and the chief toxicities were leucopenia and thrombocytopenia which were most pronounced when there was bone marrow involvement. As a result of dose limiting myelotoxicity, a dose escalation to 0.15 mg/kg/day was possible on just three occasions. These data confirm other reports of the activity of 2CDA in low grade NHL and indicate it may have activity in Hodgkin's disease. There was no demonstrable activity in poor performance status patients or those with extensively pre-treated lymphoplasmacytoid tumours.

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Year:  1993        PMID: 8094003      PMCID: PMC1968218          DOI: 10.1038/bjc.1993.24

Source DB:  PubMed          Journal:  Br J Cancer        ISSN: 0007-0920            Impact factor:   7.640


  13 in total

1.  2-Chlorodeoxyadenosine treatment of lymphoid malignancies.

Authors:  L D Piro
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2.  2-Chlorodeoxyadenosine: an effective new agent for the treatment of chronic lymphocytic leukemia.

Authors:  L D Piro; C J Carrera; E Beutler; D A Carson
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3.  Mechanism of deoxyadenosine and 2-chlorodeoxyadenosine toxicity to nondividing human lymphocytes.

Authors:  S Seto; C J Carrera; M Kubota; D B Wasson; D A Carson
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4.  On the pharmacokinetics of 2-chloro-2'-deoxyadenosine in humans.

Authors:  J Liliemark; G Juliusson
Journal:  Cancer Res       Date:  1991-10-15       Impact factor: 12.701

5.  Biochemical pharmacology of 2-chlorodeoxyadenosine in malignant human hematopoietic cell lines and therapeutic effects of 2-bromodeoxyadenosine in drug combinations in mice.

Authors:  T L Avery; J E Rehg; W C Lumm; F C Harwood; V M Santana; R L Blakley
Journal:  Cancer Res       Date:  1989-09-15       Impact factor: 12.701

6.  Reporting results of cancer treatment.

Authors:  A B Miller; B Hoogstraten; M Staquet; A Winkler
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7.  Deoxycytidine kinase-mediated toxicity of deoxyadenosine analogs toward malignant human lymphoblasts in vitro and toward murine L1210 leukemia in vivo.

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Journal:  Proc Natl Acad Sci U S A       Date:  1980-11       Impact factor: 11.205

8.  2-Chlorodeoxyadenosine produces a high rate of complete hematologic remission in relapsed acute myeloid leukemia.

Authors:  V M Santana; J Mirro; C Kearns; M J Schell; W Crom; R L Blakley
Journal:  J Clin Oncol       Date:  1992-03       Impact factor: 44.544

9.  Specific toxicity of 2-chlorodeoxyadenosine toward resting and proliferating human lymphocytes.

Authors:  D A Carson; D B Wasson; R Taetle; A Yu
Journal:  Blood       Date:  1983-10       Impact factor: 22.113

10.  Lasting remissions in hairy-cell leukemia induced by a single infusion of 2-chlorodeoxyadenosine.

Authors:  L D Piro; C J Carrera; D A Carson; E Beutler
Journal:  N Engl J Med       Date:  1990-04-19       Impact factor: 91.245

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8.  Cladribine with cyclophosphamide and prednisone in the management of low-grade lymphoproliferative malignancies.

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  8 in total

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