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A phase II "window" study of topotecan in untreated patients with high risk adult acute lymphoblastic leukemia.
Clin Cancer Res. 1998 Nov; 4(11):2677-89.CC

Abstract

To further evaluate the activity of topotecan (TPT) in acute leukemia, TPT was administered (2.1 mg/m2/day for 5 days by continuous i.v. infusion) to adult patients with previously untreated acute lymphoblastic leukemia (ALL) with high-risk features (13 patients) or relapsed ALL (1 patient). Patients achieving a partial response or significant hematological improvement received a second course. All patients subsequently received standard treatment for ALL. Because complete response was achieved in only 1 of 14 patients, the study was terminated prematurely. An additional patient achieved minimal response, and a third patient normalized her hemogram despite ongoing leukemia in the marrow. Overall, six patients had significant hematological improvement (normalization of platelet and/or absolute neutrophil count). Two patients expired due to infections during induction chemotherapy. The primary nonhematological toxicities were mucositis and diarrhea. Exposure to TPT did not appear to influence the response to subsequent standard chemotherapy. The mean steady-state TPT plasma concentration, 16.1+/-1 nM, overlapped the range of LD90 values of primary human leukemia specimens. Cellular topo I content varied over a 3-fold range, encompassing levels found previously in relapsed patients. No relationship was found between topo I expression and markers of cellular proliferation or response to therapy. In contrast, low expression of the apoptosis inhibitor Bcl-2 was associated with response to TPT therapy. TPT has significant, albeit modest, single-agent activity against high-risk adult ALL. This study demonstrates the feasibility of evaluating promising new therapeutic agents in untreated patients with acute leukemia at high risk for failure with conventional therapy.

Authors+Show Affiliations

The Johns Hopkins Oncology Center, Baltimore, Maryland 21287-8963, USA. sdgore@welchlink.welch.jhu.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Clinical Trial, Phase II
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9829730

Citation

Gore, S D., et al. "A Phase II "window" Study of Topotecan in Untreated Patients With High Risk Adult Acute Lymphoblastic Leukemia." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 4, no. 11, 1998, pp. 2677-89.
Gore SD, Rowinsky EK, Miller CB, et al. A phase II "window" study of topotecan in untreated patients with high risk adult acute lymphoblastic leukemia. Clin Cancer Res. 1998;4(11):2677-89.
Gore, S. D., Rowinsky, E. K., Miller, C. B., Griffin, C., Chen, T. L., Borowitz, M., Donehower, R. C., Burks, K. L., Armstrong, D. K., Burke, P. J., Grever, M. R., & Kaufmann, S. H. (1998). A phase II "window" study of topotecan in untreated patients with high risk adult acute lymphoblastic leukemia. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 4(11), 2677-89.
Gore SD, et al. A Phase II "window" Study of Topotecan in Untreated Patients With High Risk Adult Acute Lymphoblastic Leukemia. Clin Cancer Res. 1998;4(11):2677-89. PubMed PMID: 9829730.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A phase II "window" study of topotecan in untreated patients with high risk adult acute lymphoblastic leukemia. AU - Gore,S D, AU - Rowinsky,E K, AU - Miller,C B, AU - Griffin,C, AU - Chen,T L, AU - Borowitz,M, AU - Donehower,R C, AU - Burks,K L, AU - Armstrong,D K, AU - Burke,P J, AU - Grever,M R, AU - Kaufmann,S H, PY - 1998/11/26/pubmed PY - 1998/11/26/medline PY - 1998/11/26/entrez SP - 2677 EP - 89 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin Cancer Res VL - 4 IS - 11 N2 - To further evaluate the activity of topotecan (TPT) in acute leukemia, TPT was administered (2.1 mg/m2/day for 5 days by continuous i.v. infusion) to adult patients with previously untreated acute lymphoblastic leukemia (ALL) with high-risk features (13 patients) or relapsed ALL (1 patient). Patients achieving a partial response or significant hematological improvement received a second course. All patients subsequently received standard treatment for ALL. Because complete response was achieved in only 1 of 14 patients, the study was terminated prematurely. An additional patient achieved minimal response, and a third patient normalized her hemogram despite ongoing leukemia in the marrow. Overall, six patients had significant hematological improvement (normalization of platelet and/or absolute neutrophil count). Two patients expired due to infections during induction chemotherapy. The primary nonhematological toxicities were mucositis and diarrhea. Exposure to TPT did not appear to influence the response to subsequent standard chemotherapy. The mean steady-state TPT plasma concentration, 16.1+/-1 nM, overlapped the range of LD90 values of primary human leukemia specimens. Cellular topo I content varied over a 3-fold range, encompassing levels found previously in relapsed patients. No relationship was found between topo I expression and markers of cellular proliferation or response to therapy. In contrast, low expression of the apoptosis inhibitor Bcl-2 was associated with response to TPT therapy. TPT has significant, albeit modest, single-agent activity against high-risk adult ALL. This study demonstrates the feasibility of evaluating promising new therapeutic agents in untreated patients with acute leukemia at high risk for failure with conventional therapy. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/9829730/A_phase_II_"window"_study_of_topotecan_in_untreated_patients_with_high_risk_adult_acute_lymphoblastic_leukemia_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=9829730 DB - PRIME DP - Unbound Medicine ER -