A multicenter, open, non-comparative, phase II study of the combination of cladribine (2-chlorodeoxyadenosine), cytarabine, and G-CSF as induction therapy in refractory acute myeloid leukemia - a report of the Polish Adult Leukemia Group (PALG).

Abstract

OBJECTIVES:

To evaluate the efficacy and toxicity of cladribine (2-chlorodeoxyadenosine, 2-CdA), cytarabine (Ara-C), and granulocyte-colony stimulating factor (G-CSF) (CLAG) regimen in refractory acute myeloid leukemia (AML) in the multicenter phase II study.

METHODS:

The induction chemotherapy consisted of 2-CdA 5 mg/m2, Ara-C2 g/m2, and G-CSF. In the case of partial remission (PR), a second CLAG was administered. Patients in complete remission (CR) received two consolidation courses based on HD Ara-C, mitoxantrone or idarubicine, with or without 2-CdA.

RESULTS:

Fifty-eight patients from 11 centers were registered; 50 primary resistant and eight early relapsed (CR1 < 6 months). CR was achieved in 29 (50%) patients, 19 (33%) were refractory, and 10 (17%) died early. Forty of 50 primary resistant patients received daunorubicin (DNR) and Ara-C as the first-line induction therapy (DA-7), 10 received additional 2-CdA (DAC-7). The CR rates after CLAG were 58% and 10%, respectively in each group (P = 0.015). Five of six patients with myelodysplastic syndrome (MDS)/AML achieved CR. Hematologic toxicity was the most prominent toxicity of this regimen. The overall survival (OS, 1 yr) for the 58 patients as a whole, and the 29 patients in CR were 42% and 65%, respectively. Disease-free survival (DFS, 1 yr) was 29%. Only first-line induction treatment with DA-7 significantly influenced the probability of CR after CLAG. None of the analyzed factors significantly influenced DFS and OS.

CONCLUSION:

CLAG regimen has significant anti-leukemic activity and an acceptable toxicity in refractory AML. The addition of 2-CdA to the first-line induction treatment may worsen the results of salvage with CLAG. The high CR rate in patients with MDS preceding AML deserves further observation.

• Authors: A Wrzesień-Kuś, T Robak, E Lech-Marańda, A Wierzbowska, A Dmoszyńska, M Kowal, J Hołowiecki, S Kyrcz-Krzemień, S Grosicki, S Maj, A Hellmann, A Skotnicki, W Jedrzejczak, K Kuliczkowski, Polish Adult Leukemia Group
• Journal: European journal of haematology (Eur J Haematol) Vol. 71 Issue 3 Pg. 155-62 (Sep 2003) ISSN: 0902-4441 [Print] England
• PMID: 12930315 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Cytarabine
• Granulocyte Colony-Stimulating Factor
• Cladribine

Topics

• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Cladribine (administration & dosage, adverse effects)
• Cytarabine (administration & dosage, adverse effects)
• Disease-Free Survival
• Granulocyte Colony-Stimulating Factor (administration & dosage, adverse effects)
• Humans
• Leukemia, Myeloid, Acute (complications, drug therapy, mortality)
• Myelodysplastic Syndromes (complications)
• Prognosis
• Recurrence
• Remission Induction
• Survival Rate