Table 1.
Clinical trials with reported effects of ESA in cancer patients performed between 2009 and 2014.
| Study (reference) | Type | No. of patients (cancer type) | Therapy | Support therapy | Hb control | Disease control | Observations |
|---|---|---|---|---|---|---|---|
| Mäenpää et al. (138) | N = 114 (various) | EB | ↑HRQoL | ||||
| Thomaidis et al. (139) | Ph2 | N = 118 (esophagogastric) | Cx | EB | ↑Hb (ESA) | ↑OS, RFS (ESA) | |
| AGO-ETC Moebus et al. (123) | N = 1.284 (breast) | Cx | EA | ↑Hb, ↓TF (ESA) | ↔OS, RFS | ↑TE (ESA) | |
| GINECO Weber et al. (140) | Ph2 | N = 100 (ovarian) | Cx | EA | ↓NT | ||
| Ohashi et al. (141) | Meta | N = 511 (CIA, various) | Cx | DP, EB | ↓TF (ESA) | ↔OS, RFS | ↔TE |
| Michallet et al. (142) | N = 107 (leukemia) | Cx, T | ESA | ↑Hb, ↓TF (ESA) | ↔OS, RFS | ↑HRQoL (ESA), ↔TE | |
| Tonia et al. (124) | Meta | N = 20.102, 91 trials | ESA | ↓TF (ESA) | ↑TE, HRQoL (ESA) | ||
| Stehman et al. (143) | N = 1.864 (ovarian) | Cx | G-CSF, ESA | ↔OS | multivariate analysis | ||
| CHOICE Aerts et al. (144); Van Belle et al. (145, 146) | N = 1.887 (various) | Cx | DP | ↑Hb (ESA) | Five severe drug reactions | ||
| Kerkhofs et al. (147) | N = 113 | Cx | EA | ↑Hb (ESA) | NR | ||
| Canon et al. (125) | Ph3 | N = 705 | Cx | DP | ↑Hb (ESA) | ↑TE (ESA) | |
| Bustos et al. (126) | N = 685 (CIA, various) | Cx | DP | ↑Hb (ESA) | ↑TE (ESA) | ||
| Cabanillas et al. (148) | N = 109 (leukemia, lymphoma) | Cx | EA | ↓TF (ESA) | ↔CR | ↔HRQoL | |
| Cantrell et al. (149) | N = 343 (CIA, ovarian) | Cx | ESA | ↔OS, PFS | |||
| Fujisaka et al. (127) | Ph3 | N = 186 (CIA, various) | Cx | EB | ↑Hb (ESA) | ↔OS | ↑HRQoL, ↑TE (ESA) |
| NOGGO-AGO Blohmer et al. (150) | Ph3 | N = 257 (cervical) | Cx, Rx | EA | ↑Hb (ESA) | ↑RFS (ESA), ↔OS | ↔TE |
| PREPARE Untch et al. (128, 129) | Ph3 | N = 733 (breast) | Cx, Na | DP | ↑Hb (ESA) | ↓RFS (ESA) | ↑TE (ESA) |
| Nagel et al. (151) | Ph2 | N = 74 (SCLC) | Cx | DP | ↓TF (ESA) | ↔PFS | |
| RETRA Eisterer et al. (152) | N = 309 (various) | Cx | DP | ↓TF (ESA) | |||
| Djavan et al. (153) | N = 1.567 (prostate) | S | ESA | ↔RFS | |||
| Villegas et al. (130) | Ph2 | N = 44 (MDS) | DP | ↑TE (ESA) | |||
| Rørth et al. (154) | N = 16 (solid) | Cx | DP | ↑Hb (ESA) | ↑HRQoL (ESA) | ||
| Tjulandin et al. (155) | N = 186 (CIA, various) | Cx | ET | ↑Hb, ↓TF (ESA) | ↔AE | ||
| Esquerdo et al. (156) | N = 100 (CIA, solid) | Cx | DP | ↑Hb, ↓TF (ESA) | |||
| Chavez-MacGregor et al. (131) | Retro | N = 2.266 (breast) | Cx | ESA | ↑TE (ESA) | ||
| Gómez et al. (157) | (gastrointestinal) | Cx | EB | ↑Hb (ESA) | NR | ||
| Gomez-Alamillo et al. (158) | N = 22 (solid) | Rx, Na | EB | ↑Hb (ESA) | |||
| Schwartzberg et al. (159) | Ph2 | N = 752 (CIA, various) | Cx | DP | ↑Hb (ESA) | ↔AE | |
| Ray-Coquard et al. (160) | N = 2.912 (solid) | Cx | DP | ↑Hb (ESA) | |||
| Pronzato et al. (161) | N = 223 (breast) | Cx | EA | ↑Hb (ESA) | ↔OS, TR, AE | ↑PRO, HRQoL (ESA) | |
| Vargas et al. (162) | Ph4 | N = 157 (CIA, various) | Cx, Rx | EA | ↑Hb, ↓TF (ESA) | ↑AE (ESA) | |
| Auerbach et al. (163) | Ph2 | N = 242 (solid) | Cx, | DP, Fe | ↑Hb (Fe) | ↔AE | |
| Maccio et al. (164) | N = 148 (various) | Cx | EB, Fe | ↔Hb (Fe) | |||
| Ichinose et al. (165) | Ph2 | N = 132 (lung, ovarian) | Cx | DP | ↑Hb (ESA) | ↑HRQoL (ESA) | |
| GHSG HD15EPO Engert et al. (166) | N = 1.379 (HL) | Cx | EA | ↓TF (ESA) | ↔OS, RFS, PFS, | ↔TE | |
| Gascon et al. (135) | Ph2 | N = 153 (NSCLC) | Cx | CERA, DP | ↔Hb | ↓OS (ESA) | Terminated early |
| Muravyov et al. (167) | N = 40 (solid) | Cx | EB | ↑Hb (ESA) | |||
| Stull et al. (168) | N = 1.494 (various) | Cx | DP | ↑Hb (ESA) | ↑HRQoL (ESA) | ||
| Tjulandin et al. (169) | N = 223 (CIA, various) | Cx | ET, EA | ↑Hb (ESA) | |||
| Roddy et al. (132) | N = 79 (colorectal) | Cx | ESA | ↑TE (ESA) | |||
| Hoskin et al. (170) | N = 301 (head and neck) | Rx | EA | ↑Hb (ESA) | ↔OS, RFS | ↔AE | |
| Vansteenkiste et al. (171) | Ph3 | N = 705 (CIA, solid) | Cx | DP | ↑Hb, ↓TF (ESA) | ||
| Grobmyer et al. (172) | N = 40 (abdominal) | S | EA | ↔TF | |||
| BRAVE Aapro et al. (133) | N = 463 (breast) | Cx | EB, At | ↑TE (ESA), ↓TE (ESA, At) | |||
| Aapro et al. (134) | Meta | N = 2.297 (breast) | Cx | EB | ↔OS | ↑TE (ESA), | |
| Hernandez et al. (173) | Ph3 | N = 386 (CIA, solid) | Cx | DP | ↓TF (ESA) | ↔HRQoL, TE, | |
| Greenberg et al. (174) | Ph3 | N = 110 (MDS) | Cx | ESA, GCSF | ↔OS | ↑HRQoL (ESA) | |
| Repetto and CIPOMO Investigators (175) | N = 1.175 (various) | Cx | ESA, GCSF | ||||
| Bohlius et al. (136) | Meta | N = 13.933 (various) | ESA | ↓OS (over ↑Hb) | |||
| Lambin et al. (137) | N = 1.397 (head and neck) | Cx, Rx | ESA | ↓OS (over ↑Hb) | |||
| Tzekova et al. (176) | Ph3 | N = 216 (solid) | Cx | EZ | ↑Hb (ESA) | ↓TE (EZ), ↑HRQoL (ESA) |
Study type: Meta, meta-analysis; Ph2-4, clinical study phase 2–4; Retro, retro-analysis. Disease/cancer type: CIA, chemotherapy-induced anemia; HL, Hodgkin’s lymphoma; MDS, myelodysplastic syndrome; NSCLC, non-small-cell lung cancer; SCLC, small-cell lung cancer. Therapy: At, antithrombotic; CERA, continuous erythropoietin receptor activator; Cx, chemotherapy; DP, darbepoetin; EA, epoetin alpha; EB, epoetin beta; ESA, erythropoiesis-stimulating agent; ET, epoetin theta; EZ, epoetin zeta; Fe, iron supplementation; Na, neoadjuvant; Rx, radiotherapy; S, surgery; TF, transfusion; T, transplantation. Disease control and observations: AF, adverse effects; CR, complete remission; DFS, disease-free survival; Hb, hemoglobin; HRQoL, health-related quality of life; NR, not reported; NT, neurotoxicity; OS, overall survival; PFS, progression-free survival; PRO, patient-reported outcomes; RFS, relapse-free survival; TE, thrombotic events; TR, tumor response; ↑/ ↓/ ↔, increased/decreased/no significant difference.
Studies with indicated negative effects are marked in gray.