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Table 3 Safety and Efficacy of Dexrazoxane in Clinical Studies

From: Upfront dexrazoxane for the reduction of anthracycline-induced cardiotoxicity in adults with preexisting cardiomyopathy and cancer: a consecutive case series

First Author and Year of Publication Population Anthracycline Agent Number of Subjects Median Age (years) Baseline CV Risk Factors Dexrazoxane Administration Timing Cardiotoxicity in Dexrazoxane Arm Cardiotoxicity in Control Arm Reduced anti-tumor efficacy Incidence of Secondary Malignancy
Swain SM et al. 1997 [6] Prospective RCT, Dex vs. Placebo Adult, Advanced breast cancer Doxorubicin 534 58 (study 088001) 56 (study 088006) No difference between two groups From the beginning of therapy 15% (study 088001) 14% (study 088006) 31% (study 088001) 31% (study 088006) Lower response rate (14% difference) but no effect on overall time to progression or survival (study 088001) Not evaluated
Swain SM et al. 1997 [7] Prospective RCT, Dex vs. Placebo Adult, Advanced breast cancer Doxorubicin 201 57 No difference between two groups After a cumulative doxorubicin dose of 300 mg/m2 3% 22% No effect Not evaluated
Rabinovich A et al. 2012 [34] Retrospective, comparing cancer outcomes in Dex vs. No-Dex Adult, NHL Doxorubicin 193 70.35 Dex group had more CV risk factors 61.7% of the patients started dexrazoxane in the first or second chemotherapy cycle Not evaluated Not evaluated No effect Not evaluated
Limat S et al. 2014 [35] Retrospective, comparing two groups based on time of treatment (1994–2000 and 2001–2005) Adult, NHL Doxorubicin 180 58 No difference between two groups From the beginning of therapy (Note: Only 45% patients in 2001–05 group received Dex) 17% 1.5% Not evaluated Not evaluated
Vachhani P et al. 2017 [36]
Retrospective, consecutive patients with AML treated with Dex, baseline LVEF 40–50%
Adult, AML Daunorubicin or Mitoxantrone 6 61.5 No control group 50% (3/6) had Dex from the beginning of therapy. The rest 3 had Dex after median of 340 mg/m2 anthracycline 16.67% (1/6 patients) No control arm Not evaluated Not evaluated
Lopez M et al. 1998 [38] Prospective RCT, Dex vs. No Dex Adult, Advanced breast cancer or soft tissue sarcoma Epirubicin Breast cancer – 95 Sarcoma - 34 Breast cancer −58 Sarcoma - 51 Not mentioned in the study. Dose of epirubicin was higher in Dex arm From the beginning of therapy 4.1% 20.8% No effect Not evaluated
Schuler MK et al. 2016 [39] Retrospective, Dex given for one of the following reasons:
1. Re-challenge,
2. Reaching the cumulative anthracycline dose and
3. Preexisting heart failure
Adult, Sarcoma Doxorubicin 32 54 No control group 27/32 patients received Dex after a median dose of 450 mg/m2 of doxorubicin 5/32 patients received Dex from the beginning of therapy (Given baseline elevated cardiac risk – CHF, CAD or arrhythmia) 7% No control arm Not evaluated Not evaluated
Lipshultz SE et al. 2004 [3] Prospective RCT, Dex vs. No Dex Children, Previously untreated high-risk ALL Doxorubicin 206 7.5 Not mentioned in the study but median cumulative dose of doxorubicin was same in both groups From the beginning of therapy 21% (elevated cTnT) 10% (Extremely elevated cTnT level) 50% (elevated cTnT 32% (Extremely elevated cTnT level) No effect Not evaluated
Chow EJ at al. 2015 [40] Long term follow-up (median 12.6 years) of 3 prospective RCT patients to evaluate effect of Dex on long-term survival Children, (T-cell acute lymphoblastic leukemia/ lymphoma, intermediate/ high-risk Hodgkin lymphoma, and low-risk Hodgkin lymphoma) Doxorubicin 1008 12.6 Not mentioned in the study but median cumulative dose of doxorubicin was same in both groups in each trial From the beginning of therapy Not reported in the study but no difference in CV mortality Not reported in the study but no difference in CV mortality No effect No effect
Asselin BL et al. 2016 [41] Prospective RCT, Dex vs. No Dex Children, T-ALL or L-NHL Doxorubicin 537 9.8 Not mentioned in the study but median cumulative dose of doxorubicin was same in both groups From the beginning of therapy Acute cardiotoxicity: 1 patient Elevated cTnT: 2.4% z scores for LV fractional shortening (3 years): −0.05 (normal) Acute cardiotoxicity: 4 patient Elevated cTnT: 8.8% z scores for LV fractional shortening (3 years): − 0.77 (abnormal) No effect No effect
Tebbi CK et al. 2007 [8] Prospective RCT, Dex vs. No Dex Children, Hodgkin’s disease treated with ABVE or dose-intensified ABVE-PC followed by low-dose radiation Doxorubicin 478 12.9 Not reported From the beginning of therapy Not reported Not reported No effect 8/10 patients with secondary malignancy in Dex arm. Standardized incidence rate was 41.86 with Dex versus 10.08 without Dex (P = 0.0231)
Shaikh F et al. 2016 [9] Meta-analysis of 17 studies (5 RCT and 12 NRSs to evaluate effects of Dex for cardioprotection and secondary malignancy Children, Variety of hematological and solid malignancies Multiple agents (predominantly doxorubicin) 4639 Variable among studies (< 18) Not reported All but one NRS administered Dex from the beginning of anthracycline therapy Dex reduced clinical or subclinical cardiotoxicity among RCTs (RR = 0.29, P = .003, NNT = 41) and NRSs (RR = 0.43, P < .001, NNT = 7) No control arm No effect RCT: Dex: 2.7% No Dex: 1.1% (RR = 2.37, P = .06). Two RCTs that used concurrent etoposide reported an increased risk of AML, while one that used cranial radiation reported an increased risk of brain tumors. NRSs: No effect
Kim H et al. 2018 [42] Retrospective, Dex vs. No Dex Children, Variety of hematological and solid malignancies Multiple agents (predominantly doxorubicin) 1453 6 Not reported but anthracycline dose was higher in Dex arm (210 mg/m2 in Dex arm vs. 150 mg/m2 in No Dex arm, p < 0.01) From the beginning of therapy Cardiac event-free survival rate of patients with more than 400 mg/m2 of anthracyclines was significantly higher in Dex group No control arm Not evaluated No effect
Getz KD et al. 2018 [43] Prospective, Comparing various treatments in children with AML, Dex given as per descrition of treating physician Children, AML Daunorubicin 1014 (only 96 had Dex) Not reported in abstract Not reported From the beginning of therapy Less declines in EF (∆EF: 0 to −4.0) Early LVSD – 6.3% More significant decline in EF (∆EF: 0 to −6.4; p < 0.05) Early LVSD – 19.2% (p = 0.005) Dex arm had non-significantly higher 3-year OS (71.9% vs 63.0%, p = 0.093) and EFS (54.4% vs 44.2%, p = 0.070) Not evaluated
  1. ABVE Adriamycin (doxorubicin), bleomycin, vincristine, etoposide, ABVE-PC Adriamycin (doxorubicin), bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide, AML acute myeloid leukemia, ALL acute lymphoblastic leukemia, cTn cardiac troponin, CV cardiovascular, Dex dexrazoxane, NHL non-Hodgkin’s lymphoma, LVEF left ventricular ejection fraction, LVSD left ventricular systolic dyscuntion, NRS non-randomized study, RCT randomized control trial