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Phase II trial of CPT-11 in myelodysplastic syndromes with excess of marrow blasts

Leukemia volume 17, pages 319–322 (2003)Cite this article

Abstract

CPT-11 is an antineoplastic agent which acts as a specific inhibitor of DNA topisomerase 1 and has a broad spectrum of activity in solid tumors. Very few studies have evaluated the activity of CPT-11 in hematological malignancies. We conducted a phase II trial of CPT-11 in 26 patients with high-risk MDS (RAEB 1: n = 4; RAEB 2: n = 9; MDS having progressed to AML: n = 10; CMML: n = 3) who could not receive anthracycline/cytarabine intensive chemotherapy. Induction therapy consisted of four courses of CPT-11 given intravenously at 200 mg/m2 every 2 weeks. Patient characteristics were: median age, 71 (range 51–77); sex, (M/F), 21/5, median % marrow blasts cells, 13.5 (range 7–52). Cytogenetics according to IPSS were: low-risk n = 13, intermediate-risk n = 6, high-risk n = 3, failure or not done n = 4. Six patients stopped treatment after only one or two courses of CPT-11 due to severe infection (n = 2), progressive disease (n = 3), acute lysis syndrome with renal failure (n = 1). In the 20 patients who received at least three cycles of CPT-11, complete remission was achieved in one case, partial remission in four cases, and hematological improvement in three cases with an overall response rate of 33% in the 26 patients. Duration of response was short (median 4 months, range 1–6 months) and median survival was 8 months (range 1–23 months). Digestive toxicity (diarrhea) occurred in 26/89 (29%) courses, but was mild (grade 1, 20% courses; grade 2 or 3, 9% courses). Hematological toxicity was difficult to assess in non-responders because of initial pancytopenia, but all the patients who responded had grade 3/4 hematological toxicity associated with grade ⩾2 infection requiring hospitalization in 18% of the courses. No other major toxicity was observed. Thus CPT-11 has an interesting activity in MDS with excess of blasts; toxicity is easily managed and most patients can be treated in the out-clinic setting. These results suggest that further evaluation of CPT-11 in MDS is warranted.

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Authors and Affiliations

  1. Institut Gustave Roussy, Villejuif, France

    V Ribrag, F Suzan, J M Vantelon & J H Bourhis

  2. Hôpital Necker, Paris, France

    G Damaj

  3. Hôpital Cochin, Paris, France

    F Dreyfus

  4. CHU Nancy, France

    A Guerci

  5. CHU Lille, France

    P Fenaux

  6. Hôpital de Jolimont, Belgium

    C Ravoet

  7. ULB, Belgium

    W Feremans

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  1. V Ribrag
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Ribrag, V., Suzan, F., Ravoet, C. et al. Phase II trial of CPT-11 in myelodysplastic syndromes with excess of marrow blasts. Leukemia 17, 319–322 (2003). https://doi.org/10.1038/sj.leu.2402726

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