Cancer Chemotherapy and Pharmacology

, Volume 63, Issue 5, pp 793–798 | Cite as

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

  • Nancy L. BartlettEmail author
  • Jeffrey L. Johnson
  • Nina Wagner-Johnston
  • Mark J. Ratain
  • Bruce A. Peterson
  • For the Cancer and Leukemia Group B
Original Article



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.


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.


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.


Single agent 9-AC has modest activity in aggressive non-Hodgkin’s lymphomas.


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



The research for CALGB 9551was supported, in part, by grants from the National Cancer Institute (CA31946) to the Cancer and Leukemia Group B (Richard L. Schilsky, MD, Chairman) and to the CALGB Statistical Center (Stephen George, PhD, CA33601). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute.


  1. 1.
    Ohno R, Okada K, Masaoka T et al (1990) An early Phase II study of CPT-11: a new derivative of camptothecin, for the treatment of leukemia and lymphoma. J Clin Oncol 8(11):1907–1912PubMedGoogle Scholar
  2. 2.
    Ota K, Ohna R, Shirakawa S et al (1994) Late Phase II study of irinotecan hydrochloride (CPT-11) in the treatment of malignant lymphoma and acute leukemia. The CPT-11 Research Group for Hematologic Malignancies. Japanese J Ca Chemoth 21(7):1047–1055 (Japanese)Google Scholar
  3. 3.
    Sarris AH, Romaguera J, Hagemeister FB et al (2001) Irinotecan in relapsed or refractory non-Hodgkins lymphoma. Oncology (Williston Park) 15(7 Suppl 8):53–56Google Scholar
  4. 4.
    Kraut EH, Balcerzak SP, Young D et al (2002) A phase II study of topotecan in non-Hodgkin’s lymphoma: an Ohio State University phase 2 consortium study. Cancer Invest 20(8):174–179PubMedCrossRefGoogle Scholar
  5. 5.
    Younes A, Preti HA, Hagemeister FB et al (2001) Paclitaxel plus topotecan treatment for patients with relapsed or refractory aggressive non-Hodgkin’s lymphoma. Ann Oncol 12(7):923–927PubMedCrossRefGoogle Scholar
  6. 6.
    Chen AY, Yu C, Potmesil M et al (1991) Camptothecin overcomes MDR1-mediated resistance in human KB carcinoma cells. Cancer Res 51:6039–6044PubMedGoogle Scholar
  7. 7.
    Hsiang YH, Liu LF, Wall ME et al (1989) DNA topoisomerase I mediated DNA cleavage and cytotoxicity of camptothecin analogs. Cancer Res 49:4385–4389PubMedGoogle Scholar
  8. 8.
    Ulukan H, Swaan PW (2002) Camptothecins: a review of their chemotherapeutic potential. Drugs 62(14):2039–2057PubMedCrossRefGoogle Scholar
  9. 9.
    Leguizamo J, Quinn M, Takimoto CH et al (2003) A phase I study of 9-aminocamptothecin as a colloidal dispersion formulation given as a fortnightly 72-h infusion. Cancer Chemother Pharmacol 52(4):333–338PubMedCrossRefGoogle Scholar
  10. 10.
    Rubin E, Wood V, Bharti A et al (1995) A phase I and pharmacokinetic study of a new camptothecin derivative, 9-aminocamptothecin. Clin Canc Res 1:269–276Google Scholar
  11. 11.
    Dahut W, Harold N, Takimoto C et al (1996) Phase I and pharmacologic study of 9-aminocamptothecin given by 72-hour infusion in adult cancer patients. J Clin Oncol 14(4):1236–1244PubMedGoogle Scholar
  12. 12.
    Eder JP, Supko JG, Lynch T et al (1998) Phase I trial of the colloidal dispersion formulation of 9-amino-20(S)-camptothecin administered as a 72-hour continuous intravenous infusion. Clin Canc Res 4(2):317–324Google Scholar
  13. 13.
    Wilson WH, Little R, Pearson D et al (1998) Phase II and dose-escalation with or without granulocyte colony-stimulating factor study of 9-aminocamptothecin in relapsed and refractory lymphomas. J Clin Oncol 16(7):2345–2351PubMedGoogle Scholar
  14. 14.
    Takimoto CH, Klecker RW, Dahut WL et al (1994) Analysis of the active lactone form of 9-aminocamptothecin in plasma using solid phase extraction and high performance liquid chromatography. J Chromatogr B Biomed Appl 655:97–104PubMedCrossRefGoogle Scholar
  15. 15.
    Minami H, Lad TE, Nicholas MK et al (1999) Pharmacokinetics and pharmacodynamics of 9-aminocamptothecin infused over 72 hours in Phase II studies. Clin Cancer Res 5:1325–1330PubMedGoogle Scholar
  16. 16.
    Eder JP, Chan V, Wong J et al (1998) Sequence effect of irinotecan (CPT-11) and topoisomerase II inhibitors in vivo. Cancer Chemother Pharmacol 42:327–335PubMedCrossRefGoogle Scholar
  17. 17.
    Whitacre CM, Zborowska E, Gordon NH et al (1997) Topotecan increases topoisomerase IIα levels and sensitivity to treatment with etoposide in schedule-dependent process. Cancer Res 57:1425–1428PubMedGoogle Scholar
  18. 18.
    Bonner JA, Kozelsky TF (1996) The significance of the sequence of administration of topotecan and etoposide. Cancer Chemother Pharmacol 39:109–112PubMedCrossRefGoogle Scholar
  19. 19.
    Smith SM, Johnson JL, Niedzwiecki D et al (2006) Sequential doxorubicin and topotecan in relapsed/refractory aggressive NHL: results of CALGB 59906. Leuk Lymphoma 47:1511–1517PubMedCrossRefGoogle Scholar
  20. 20.
    Kancherla RR, Nair JS, Ahmed T et al (2001) Evaluation of topotecan and etoposide for non-Hodgkin lymphoma: correlation of topoisomerase-DNA complex formation with clinical response. Cancer 91(3):463–471PubMedCrossRefGoogle Scholar
  21. 21.
    Crump M, Couban S, Meyer R et al (2002) Phase II study of sequential topotecan and etoposide in patients with intermediate grade non-Hodgkin’s lymphoma: a National Cancer Institute of Canada Clinical Trials Group Study. Leuk Lymphoma 43(8):1581–1587PubMedCrossRefGoogle Scholar
  22. 22.
    Younes A, Preti HA, Hagemeister FB et al (2001) Paxlitaxel plus topotecan for patients with relapsed or refractory aggressive non-Hodgkin’s lymphoma. Ann Oncol 12:923–927PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Nancy L. Bartlett
    • 1
    Email author
  • Jeffrey L. Johnson
    • 2
  • Nina Wagner-Johnston
    • 1
  • Mark J. Ratain
    • 3
  • Bruce A. Peterson
    • 4
  • For the Cancer and Leukemia Group B
  1. 1.Washington University School of MedicineSt. LouisUSA
  2. 2.CALGB Statistical CenterDuke University Medical CenterDurhamUSA
  3. 3.University of ChicagoChicagoUSA
  4. 4.University of MinnesotaMinneapolisUSA

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