Phase II study of 9-aminocamptothecin in previously treated lymphomas: Results of Cancer and Leukemia Group B 9551

Nancy L. Bartlett, Jeffrey L. Johnson, Nina Wagner-Johnston, Mark J. Ratain, Bruce A. Peterson

Research output: Contribution to journalArticle

Abstract

Purpose: To evaluate the efficacy and toxicity of the topoisomerase I inhibitor, 9-aminocamptothecin (9-AC), in patients with relapsed lymphoma and to correlate 9-AC plasma concentrations with response and toxicity. Methods: Eligible patients had relapsed Hodgkin lymphoma (HL) treated with one or two prior regimens, low grade non-Hodgkin's lymphoma (NHL) treated with one or two prior regimens, or aggressive NHL treated with one prior regimen. The first nine patients received 9-AC dimethylacetamide 0.85 mg/m2 per day intravenously over 72 h every 2 weeks and the remaining 27 patients received 9-AC/colloidal dispersion 1.1 mg/m2 per day. Patients received a minimum of three cycles unless progression or intolerable toxicity occurred. Responding patients received two cycles past best response with a minimum of six cycles. Results: CALGB 9551 accrued 37 patients from April 1996 through October 2000; one patient with HD, 18 patients with indolent lymphoma, and 17 patients with aggressive lymphoma. The overall response rate was 17%, with response rates of 11% (2 partial responses) in patients with indolent histologies and 23% (1 complete response, 3 partial responses) in patients with aggressive histologies. The patient with HD did not respond. Response rates were similar for both drug formulations. The median remission duration for the six responders was 6.5 months, with one remission lasting longer than 12 months. Significant grade 3 and 4 toxicities included neutropenia (66%), anemia (31%), and thrombocytopenia (36%), with 20% of patients experiencing grade 3 or 4 infection. No treatment related deaths occurred. Steady state serum concentrations did not correlate with patient response or toxicity. Conclusion: Single agent 9-AC has modest activity in aggressive non-Hodgkin's lymphomas.

Original languageEnglish (US)
Pages (from-to)793-798
Number of pages6
JournalCancer Chemotherapy and Pharmacology
Volume63
Issue number5
DOIs
StatePublished - Apr 2009
Externally publishedYes

Fingerprint

9-aminocamptothecin
Toxicity
Lymphoma
Leukemia
Histology
Neoplasms
Topoisomerase I Inhibitors
Non-Hodgkin's Lymphoma
Plasmas

Keywords

  • 9-Aminocamptothecin (9-AC)
  • Pharmacokinetics
  • Relapsed non-Hodgkin's lymphoma
  • Topoisomerase I inhibitor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Toxicology

Cite this

Phase II study of 9-aminocamptothecin in previously treated lymphomas : Results of Cancer and Leukemia Group B 9551. / Bartlett, Nancy L.; Johnson, Jeffrey L.; Wagner-Johnston, Nina; Ratain, Mark J.; Peterson, Bruce A.

In: Cancer Chemotherapy and Pharmacology, Vol. 63, No. 5, 04.2009, p. 793-798.

Research output: Contribution to journalArticle

Bartlett, Nancy L. ; Johnson, Jeffrey L. ; Wagner-Johnston, Nina ; Ratain, Mark J. ; Peterson, Bruce A. / Phase II study of 9-aminocamptothecin in previously treated lymphomas : Results of Cancer and Leukemia Group B 9551. In: Cancer Chemotherapy and Pharmacology. 2009 ; Vol. 63, No. 5. pp. 793-798.
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abstract = "Purpose: To evaluate the efficacy and toxicity of the topoisomerase I inhibitor, 9-aminocamptothecin (9-AC), in patients with relapsed lymphoma and to correlate 9-AC plasma concentrations with response and toxicity. Methods: Eligible patients had relapsed Hodgkin lymphoma (HL) treated with one or two prior regimens, low grade non-Hodgkin's lymphoma (NHL) treated with one or two prior regimens, or aggressive NHL treated with one prior regimen. The first nine patients received 9-AC dimethylacetamide 0.85 mg/m2 per day intravenously over 72 h every 2 weeks and the remaining 27 patients received 9-AC/colloidal dispersion 1.1 mg/m2 per day. Patients received a minimum of three cycles unless progression or intolerable toxicity occurred. Responding patients received two cycles past best response with a minimum of six cycles. Results: CALGB 9551 accrued 37 patients from April 1996 through October 2000; one patient with HD, 18 patients with indolent lymphoma, and 17 patients with aggressive lymphoma. The overall response rate was 17{\%}, with response rates of 11{\%} (2 partial responses) in patients with indolent histologies and 23{\%} (1 complete response, 3 partial responses) in patients with aggressive histologies. The patient with HD did not respond. Response rates were similar for both drug formulations. The median remission duration for the six responders was 6.5 months, with one remission lasting longer than 12 months. Significant grade 3 and 4 toxicities included neutropenia (66{\%}), anemia (31{\%}), and thrombocytopenia (36{\%}), with 20{\%} of patients experiencing grade 3 or 4 infection. No treatment related deaths occurred. Steady state serum concentrations did not correlate with patient response or toxicity. Conclusion: Single agent 9-AC has modest activity in aggressive non-Hodgkin's lymphomas.",
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AU - Bartlett, Nancy L.

AU - Johnson, Jeffrey L.

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AU - Ratain, Mark J.

AU - Peterson, Bruce A.

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N2 - Purpose: To evaluate the efficacy and toxicity of the topoisomerase I inhibitor, 9-aminocamptothecin (9-AC), in patients with relapsed lymphoma and to correlate 9-AC plasma concentrations with response and toxicity. Methods: Eligible patients had relapsed Hodgkin lymphoma (HL) treated with one or two prior regimens, low grade non-Hodgkin's lymphoma (NHL) treated with one or two prior regimens, or aggressive NHL treated with one prior regimen. The first nine patients received 9-AC dimethylacetamide 0.85 mg/m2 per day intravenously over 72 h every 2 weeks and the remaining 27 patients received 9-AC/colloidal dispersion 1.1 mg/m2 per day. Patients received a minimum of three cycles unless progression or intolerable toxicity occurred. Responding patients received two cycles past best response with a minimum of six cycles. Results: CALGB 9551 accrued 37 patients from April 1996 through October 2000; one patient with HD, 18 patients with indolent lymphoma, and 17 patients with aggressive lymphoma. The overall response rate was 17%, with response rates of 11% (2 partial responses) in patients with indolent histologies and 23% (1 complete response, 3 partial responses) in patients with aggressive histologies. The patient with HD did not respond. Response rates were similar for both drug formulations. The median remission duration for the six responders was 6.5 months, with one remission lasting longer than 12 months. Significant grade 3 and 4 toxicities included neutropenia (66%), anemia (31%), and thrombocytopenia (36%), with 20% of patients experiencing grade 3 or 4 infection. No treatment related deaths occurred. Steady state serum concentrations did not correlate with patient response or toxicity. Conclusion: Single agent 9-AC has modest activity in aggressive non-Hodgkin's lymphomas.

AB - Purpose: To evaluate the efficacy and toxicity of the topoisomerase I inhibitor, 9-aminocamptothecin (9-AC), in patients with relapsed lymphoma and to correlate 9-AC plasma concentrations with response and toxicity. Methods: Eligible patients had relapsed Hodgkin lymphoma (HL) treated with one or two prior regimens, low grade non-Hodgkin's lymphoma (NHL) treated with one or two prior regimens, or aggressive NHL treated with one prior regimen. The first nine patients received 9-AC dimethylacetamide 0.85 mg/m2 per day intravenously over 72 h every 2 weeks and the remaining 27 patients received 9-AC/colloidal dispersion 1.1 mg/m2 per day. Patients received a minimum of three cycles unless progression or intolerable toxicity occurred. Responding patients received two cycles past best response with a minimum of six cycles. Results: CALGB 9551 accrued 37 patients from April 1996 through October 2000; one patient with HD, 18 patients with indolent lymphoma, and 17 patients with aggressive lymphoma. The overall response rate was 17%, with response rates of 11% (2 partial responses) in patients with indolent histologies and 23% (1 complete response, 3 partial responses) in patients with aggressive histologies. The patient with HD did not respond. Response rates were similar for both drug formulations. The median remission duration for the six responders was 6.5 months, with one remission lasting longer than 12 months. Significant grade 3 and 4 toxicities included neutropenia (66%), anemia (31%), and thrombocytopenia (36%), with 20% of patients experiencing grade 3 or 4 infection. No treatment related deaths occurred. Steady state serum concentrations did not correlate with patient response or toxicity. Conclusion: Single agent 9-AC has modest activity in aggressive non-Hodgkin's lymphomas.

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