Phase II trial of CPT-11 in myelodysplastic syndromes with excess of marrow blasts.
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/m(2) 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.
Ribrag
V
V
Institut Gustave Roussy, Villejuif, France.
Suzan
F
F
Ravoet
C
C
Feremans
W
W
Guerci
A
A
Dreyfus
F
F
Damaj
G
G
Vantelon
J M
JM
Bourhis
J H
JH
Fenaux
P
P
D000368:Aged; D000754:Anemia, Refractory, with Excess of Blasts / Q000188:drug therapy*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001752:Blast Crisis; D001853:Bone Marrow / Q000473:pathology*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D015470:Leukemia, Myeloid, Acute; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D016019:Survival Analysis; D013997:Time Factors
D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin