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Clinical Trial
. 2010 Jan;148(1):48-58.
doi: 10.1111/j.1365-2141.2009.07919.x. Epub 2009 Oct 11.

Sequential phase II Southwest Oncology Group studies (S0112 and S0301) of daunorubicin and cytarabine by continuous infusion, without and with ciclosporin, in older patients with previously untreated acute myeloid leukaemia

Thomas R Chauncey  1 , Holly Gundacker, Mazyar Shadman, Alan F List, Shaker R Dakhil, Harry P Erba, Marilyn L Slovak, I-Ming Chen, Cheryl L Willman, Kenneth J Kopecky, Frederick R Appelbaum
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Clinical Trial

Sequential phase II Southwest Oncology Group studies (S0112 and S0301) of daunorubicin and cytarabine by continuous infusion, without and with ciclosporin, in older patients with previously untreated acute myeloid leukaemia

Thomas R Chauncey et al. Br J Haematol. 2010 Jan.

Abstract

Attempts to overcome multi-drug resistance in acute myeloid leukaemia (AML) have been limited by toxicities. To investigate the effect of reducing peak drug levels, we performed sequential phase II studies using continuous infusion daunorubicin and cytarabine without (AD) and then with ciclosporin (ADC) in older patients with AML. Untreated patients (age 56+ years) received daunorubicin (45 mg/m2 per day for 3 d) and cytarabine (200 mg/m2 per day for 7 d), both by continuous infusion, without (S0112, 60 patients) and then with (S0301, 50 patients) the addition of ciclosporin. Complete response (CR) rates were 38% on S0112 and 44% on S0301. Fatal induction toxicities occurred in 17% and 12% respectively, arising primarily from infection and haemorrhage. Median overall and relapse-free survival was 7 and 8 months for AD respectively, and 6 and 14 months for ADC. Patients with phenotypic or functional P-glycoprotein had somewhat higher CR rates with ADC than AD, although confidence intervals overlapped. In these sequential trials, continuous infusion AD produced CR rates comparable to those with bolus daunorubicin. The addition of ciclosporin did not cause undue toxicities, produced a similar CR rate, and possibly improved relapse-free survival. Further correlate analyses did not identify a subpopulation specifically benefitting from the addition of ciclosporin.

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Figures

Figure 1
Figure 1
S0112 Overall Survival
Figure 2
Figure 2
S0112: Relapse Free Survival
Figure 3
Figure 3
S0301 revised eligibility: Overall Survival
Figure 4
Figure 4
S0301 revised eligibility: Relapse Free Survival
See this image and copyright information in PMC

References

    1. Advani R, Visani G, Milligan D, Saba H, Tallman M, Rowe JM, Wiernik PH, Ramek J, Dugan K, Lum B, Villena J, Davis E, Paietta E, Litchman M, Covelli A, Sikic B, Greenberg P. Treatment of poor prognosis AML patients using PSC833 (valspodar) plus mitoxantrone, etoposide, and cytarabine (PSC-MEC) Adv Exp Med Biol. 1999;457:47–56. - PubMed
    1. Anderson JE, Kopecky KJ, Willman CL, Head D, O’Donnell MR, Luthardt FW, Norwood TH, Chen IM, Balcerzak SP, Johnson DB, Appelbaum FR. Outcome after induction chemotherapy for older patients with acute myeloid leukemia is not improved with mitoxantrone and etoposide compared to cytarabine and daunorubicin: a Southwest Oncology Group study. Blood. 2002;100:3869–76. - PubMed
    1. Appelbaum FR, Gundacker H, Head DR, Slovak ML, Willman CL, Godwin JE, Anderson JE, Petersdorf SH. Age and acute myeloid leukemia. Blood. 2006;107:3481–5. - PMC - PubMed
    1. Baer MR, George SL, Dodge RK, O’Loughlin KL, Minderman H, Caligiuri MA, Anastasi J, Powell BL, Kolitz JE, Schiffer CA, Bloomfield CD, Larson RA. Phase 3 study of the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age and older with acute myeloid leukemia: Cancer and Leukemia Group B Study 9720. Blood. 2002;100:1224–32. - PubMed
    1. Becton D, Dahl GV, Ravindranath Y, Chang MN, Behm FG, Raimondi SC, Head DR, Stine KC, Lacayo NJ, Sikic BI, Arceci RJ, Weinstein H, Pediatric Oncology Group Randomized use of cyclosporin A (CsA) to modulate P-glycoprotein in children with AML in remission: Pediatric Oncology Group Study 9421. Blood. 2006;107:1315–24. - PMC - PubMed

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