Sequential high-dose cytarabine and mitoxantrone (S-HAM) versus standard double induction in acute myeloid leukemia-a phase 3 study.

Abstract

Dose-dense induction with the S-HAM regimen was compared to standard double induction therapy in adult patients with newly diagnosed acute myeloid leukemia. Patients were centrally randomized (1:1) between S-HAM (2nd chemotherapy cycle starting on day 8 = "dose-dense") and double induction with TAD-HAM or HAM(-HAM) (2nd cycle starting on day 21 = "standard"). 387 evaluable patients were randomly assigned to S-HAM (N = 203) and to standard double induction (N = 184). The primary endpoint overall response rate (ORR) consisting of complete remission (CR) and incomplete remission (CRi) was not significantly different (P = 0.202) between S-HAM (77%) and double induction (72%). The median overall survival was 35 months after S-HAM and 25 months after double induction (P = 0.323). Duration of critical leukopenia was significantly reduced after S-HAM (median 29 days) versus double induction (median 44 days)-P < 0.001. This translated into a significantly shortened duration of hospitalization after S-HAM (median 37 days) as compared to standard induction (median 49 days)-P < 0.001. In conclusion, dose-dense induction therapy with the S-HAM regimen shows favorable trends but no significant differences in ORR and OS compared to standard double induction. S-HAM significantly shortens critical leukopenia and the duration of hospitalization by 2 weeks.

• Authors: Jan Braess, Susanne Amler, Karl-Anton Kreuzer, Karsten Spiekermann, Hans Walter Lindemann, Eva Lengfelder, Ullrich Graeven, Peter Staib, Wolf-Dieter Ludwig, Harald Biersack, Yon-Dschun Ko, Michael J Uppenkamp, Maike De Wit, Stefan Korsten, Rudolf Peceny, Tobias Gaska, Xaver Schiel, Dirk M Behringer, Michael G Kiehl, Bettina Zinngrebe, Gerald Meckenstock, Eva Roemer, Dirk Medgenberg, Ernst Spaeth-Schwalbe, Gero Massenkeil, Heidrun Hindahl, Rainer Schwerdtfeger, Guido Trenn, Cristina Sauerland, Raphael Koch, Martin Lablans, Andreas Faldum, Dennis Görlich, Stefan K Bohlander, Stephanie Schneider, Annika Dufour, Christian Buske, Michael Fiegl, Marion Subklewe, Birgit Braess, Michael Unterhalt, Anja Baumgartner, Bernhard Wörmann, Dietrich Beelen, Wolfgang Hiddemann, AML-CG
• Journal: Leukemia (Leukemia) Vol. 32 Issue 12 Pg. 2558-2571 (12 2018) ISSN: 1476-5551 [Electronic] England
• PMID: 30275528 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial)

Chemical References

• Cytarabine
• Mitoxantrone

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Cytarabine (administration & dosage)
• Female
• Humans
• Leukemia, Myeloid, Acute (drug therapy)
• Male
• Middle Aged
• Mitoxantrone (administration & dosage)
• Remission Induction (methods)
• Young Adult