TABLE 2.
Overview of 24 articles included in the literature review examining chemotherapeutics other than glucocorticoids a : summary of study characteristics, study design and stated basis for equivalence
| Article | Study population | Date of recruitment | Children/Adults b | Country | Number of patients | Study design | Study objective | Stated basis for equivalence and respective reference (only references since the year 1985) | Conversion factors provided for | Remark |
|---|---|---|---|---|---|---|---|---|---|---|
| Allodji (2021) 6 | Childhood cancer survivors; Cases: secondary leukemia | 1930–2000 | Children at diagnosis | France, United Kingdom, United States, Canada, Italy, and the Netherlands | 147 cases/522 controls | Pooled data from four nested case–control studies | Risk of secondary leukemia in relation to chemotherapy | Hematological toxicity based on Green et al. 2014 8 | AA | Additional factor for dacarbazine in article |
| Blanco (2012) 33 | Childhood cancer patients treated at member organization of Children's Oncology Group (COG); Cases: with additional cardiomyopathy | 1966–2008 | Children and adolescents ≤21 years at diagnosis | Several | 170 cases/317 controls | Case–control study | Dose‐dependent risk of anthracycline‐related cardiomyopathy | Cardiotoxicity based on Lehmann et al. 2000 32 | A | Supplement of Blanco 2012 33 presents factors different from Lehmann 2000 32 |
| Casagranda (2016) 7 | Cohort of Childhood Cancer Registry Rhônes‐Alpes Region with all types of first and second primary | 1987–2004 (diagnosis of first primary) | Children | France | 64 cases/190 controls | Nested case–control‐study | Secondary neoplasia comparing chemotherapy from different groups | “hematologic toxicity or rules of substitution” based on Guérin 2003 23 and Tucker 1987 35 | AA, A, E, PD | Factors presented in article are identical to Guérin 2007, 3 not to Guérin 2003 23 |
| Children's Oncology Group (2018) 10 | Childhood Cancer Survivors | – | Children and adolescents | – | – | Guideline developed from a literature review | – | Cardiotoxicity based on literature review for this guideline | A | – |
| Creutzig (2007) 36 | Children with primary or secondary AML | 1993–2003 (treatment) | Children | Germany | 1207 | Follow‐up after clinical trial | Cardiotoxicity | Cardiotoxicity (not explicitly stated, assumed due to outcome of the study) based on 37 , 38 , 39 | A | References in article not mentioning a definitive factor 37 , 38 , 39 |
| Feig (1996) 40 | Children with acute lymphatic leukemia at first bone marrow relapse from Children's Cancer Group (CCG) | 1990–1992 | Children and adolescents <21 years at diagnosis | USA, Canada | 92 | Randomized Clinical Trial | Event‐free survival | “Isodose conversion factor” based on Berman 1991 41 and Wiernik 1992 42 | A | Conversion factors used in references of the article were slightly different from those used in article itself; references in article refer to clinical trials comparing idarubicin versus daunorubicin— > references not included additionally |
| Feijen (2015) 30 | Childhood cancer survivors | 1962–2002 | Children and adolescents <25 years at diagnosis | Several | 15 815 | Cohort studies | Hazard Ratio for cardiotoxicity (Heart failure) comparing Daunorubicin to Doxorubicin | Cardiotoxicity assumed based on references stated in introduction | A | Conversion factors concluded from calculated hazard ratio not included |
| Feijen (2019) 34 | Childhood cancer survivors | 1962–2005 | Children and adolescents <23 years at diagnosis | Several | 28 423 | Cohort studies | Hazard Ratio for cardiotoxicity (Heart failure) comparing different anthracyclines | Cardiotoxicity assumed based on references stated in introduction | A | Conversion factors concluded from calculated hazard ratio not included |
| Green (2014) 8 | Literature review | – | Not stated | Several | Literature review | Literature review | Literature review on hematological toxicity, comparison of Alkylating Agent Dose (AAD) with developed CED (cyclophosphamide equivalent dose) | Hematological toxicity based on literature review in article | AA | – |
| Guerin (2007) 3 | Childhood cancer survivors from solid tumor | 1942–1986 | Children at diagnosis | France, UK | 153 cases/442 controls | Nested case–control study in a European cohort | Risk of secondary neoplasia in relation to chemotherapy | “Hematological toxicity or substitution rules” based on Le Deley 2003 4 | AA, A, E, PD, VA | Four additional factors not mentioned in Le Deley 2003, 4 but in Guerin 2007 3 |
| Henderson (2012) 43 | Childhood cancer survivors with (cases) or without (controls) secondary sarcomas | 1970–1986 (first diagnosis), 2000 (baseline) | Children and adolescents <21 years at diagnosis | USA, Canada | 105 cases/422 controls | Nested case–control study in the Childhood Cancer Survivor Study | Secondary sarcoma comparing chemotherapy from different groups | Not stated | A, E, PD | – |
| Launchbury (1993) 17 | Literature review | – | Not stated | Several | Literature review | Literature review | Comparison of characteristics, therapeutic activity and toxicity of epirubicin and daunorubicin | Antitumour efficacy based on literature review in the article | A | – |
| Le Deley (2003) 4 | Childhood cancer survivors of a solid tumor with (cases) or without (controls) secondary leukemia | 1980 (first neoplasia), secondary neoplasia up to 1999 | Children at diagnosis | France | 61 cases/196 controls | Case–control study | Secondary leukemia comparing chemotherapy from different groups | “Hematologic toxicity or substitution rules”; reference not stated | AA, A, E, PD | – |
| Lehmann (2000) 32 | Consecutive patients with AML, ALL, CML, multiple myeloma or breast cancer and hematopoetic stem cell transplantation | 1985–1994 | Adolescents and Adults between 17 and 62 years old | Sweden | 148 | Case series | Cardiac systolic function with anthracycline dose as risk factor | “Equipotency of anthracycline doses and the cardiotoxic potential of the drugs” based on two references after the year 1985 | A | References in the article are literature reviews without a definitive factor 44 , 45 |
| Messinger (1999) 46 | Patients with acute lymphoblastic leukemia | – | Children and adolescents up to 21 years (most studies) | Several | Literature review | Literature review | Benefit of anthracyclines | Equipotency assumed due to reference to 17 | A | Reference 17 in the article contains only factor for epirubicin |
| Mouridsen (1990) 16 | Patients with breast cancer | – | Adults (not stated, but most likely because of breast cancer) | Literature review | Literature review | Review of phase II and phase III trials | Efficacy of anthracyclines (comparison of response rates) | Hematological and non‐hematological toxicity and cardiotoxicity based on review performed in the article | A | – |
| Mulrooney (2009) 28 | Survivors of childhood cancer in the Childhood Cancer Survivor Study (CCSS) | 1970–1986 (enrolment), 2000–2002 (follow‐up) | Children and adolescents <21 years at diagnosis | USA | 14 358 survivors and 3899 siblings | Retrospective cohort study | Cardiac outcomes | Basis for equivalence not stated; factors based on Pai 2000 47 | A | Reference in the article is review without explicit factors 47 |
| Mulrooney (2016) 5 | Survivors of childhood cancer in the St. Jude Lifetime Cohort Study | 2013 (follow‐up) | Children (“childhood cancer”) at diagnosis | USA | 1853 | Cross‐sectional study | Cardiotoxicity | “Isotoxic equivalents” based on Le Deley 2003 4 : “hematologic toxicity or substitution rules” | A | Idarubicin mentioned in Mulrooney 2016, 5 but not in Le Deley 2003 4 |
| Ozols (1985) 31 | Advanced ovarian cancer patients refractory to standard therapy | – | Adults (assumed) | USA (assumed) | Several clinical trials | Several clinical trials and in‐vitro studies comparing high dose cisplatin and high dose carboplatin | Clinical activity and toxicity, in vitro and clinical trial | “Clinically active” based on literature before 1985 | PD | – |
| Schramm (2019) 9 | Children with acute lymphatic leukemia | 2003–2010 (inclusion) | Children | Germany | 773 | Clinical trial | Survival (Overall Survival, Event‐free survival) | Not stated | Asp | – |
| Smibert (2004) 29 | Childhood cancer patients with anthracycline exposure more than 12 month after anthracycline treatment; controls from healthy siblings and patient peers | 1977–1995 (diagnosis) | Children at diagnosis | Australia (authors) | 110 cases/31 controls | Cross‐sectional, non‐randomized study | Cardiac outcome of different doses of anthracyclines and alkylating agents | Anthracyclines: “Myelosuppressive potency”; no reference stated | A | – |
| Sorensen (2003) 48 | Acute lymphoblastic leukemia survivors and Wilms tumor survivors | 1970–1990 (treatment of Wilms Tumor) | Children at diagnosis | UK | 101 acute lymphoblastic leukemia survivors, 83 Wilms tumor survivors and 100 controls | Prospective, longitudinal study | Cardiac toxicity of different doses of anthracyclines | Cardiac toxicity based on the assumption of equivalence of cardiac toxicity between daunorubicin and doxorubicin | A | – |
| Wang (2022) 49 | Childhood Cancer survivors included in seven cohorts | 1946–2012 (diagnosis)—2021 (follow‐up) | Children and adolescents <21 years at diagnosis | Europe, North America | 21 892 | Pooled Individual patient data cohort | Subsequent breast cancer | Hematological toxicity assumed due to reference to cyclophosphamide equivalent dose; factors based on cyclophosphamide equivalent dose | AA | – |
| Winick (1993) 50 | Patients with acute lymphoblastic leukemia treated with etoposide | 1986–1991 (diagnosis) | Children | USA | 205 | Follow‐up of consecutive patients | Event‐free survival, secondary AML, no comparison group | Not stated; factors based on literature before 1985 | E | – |
Abbreviations: A, anthracyclines; AA, alkylating agents; ALL, acute lymphatic leukemia; AML, acute myelocytic leukemia; Asp, asparaginase; CML, chronic myelocytic leukemia; E, epipodophyllotoxins; PD, platinum derivates; VA, vinca alkaloids.
a
Articles which (1) mentioned a conversion factor or doses which permitted the calculation of a conversion factor, (2) have been published since the year 1985 and (3) of which a full‐text in English or German was available (see Table 1).
b
In studies on childhood cancer survivors, the inclusion in the study might have taken place as adults. The age groups were defined as follows: children: below the age of 18; adults: above the age of 18; adolescents: age 16–25 (only mentioned if there were mixed groups of either adolescents and adults or children and adolescents).