TY - JOUR
T1 - Predictors for doxorubicin-induced hematological toxicity and its association with outcome in advanced soft tissue sarcoma patients; a retrospective analysis of the EORTC-soft tissue and bone sarcoma group database
AU - Sleijfer, Stefan
AU - Rizzo, Elisa
AU - Litière, Saskia
AU - Mathijssen, Ron H J
AU - Judson, Ian Robert
AU - Gelderblom, Hans
AU - Van Der Graaf, Winette T A
AU - Gronchi, Alessandro
PY - 2018/8
Y1 - 2018/8
N2 - INTRODUCTION: As both anti-tumour effects and toxicity are thought to be dose-dependent, patients with the greatest toxicity may also have the best outcome. We assessed whether severity of doxorubicin-induced hematological toxicity is associated with outcome in advanced soft tissue sarcoma (STS) patients. In addition, risk factors for hematological toxicity were explored.METHODS: Worst haematological toxicities (anaemia, leukopenia, neutropenia and thrombocytopenia) seen during treatment were scored according to CTCAE toxicity score. Differences in overall survival (OS), progression free survival (PFS) and response rate (RR) between patients with or without high haematological toxicity (grades 0-2 vs. 3-4) were assessed using conventional statistical tests. Associations between baseline characteristics and hematological toxicity were established using logistic multivariate regression.RESULTS: In 557 patients eligible for this analysis, 47.2% of the patients received at least six cycles of treatment; 45% stopped treatment early due to progression, 3% because of toxicity. Relative dose intensity (RDI) was constant over the cycles. OS, PFS, and RR did not differ between patients with grade 3/4 toxicity during treatment versus those with grade 1/2. Risk factors for grade 3/4 haematological toxicity, in particular neutropenia, were age above 60 years, low BMI, and female gender.CONCLUSION: In this large series, risk factors for haematological toxicity in STS patients receiving doxorubicin monotherapy were revealed. The finding that there was no association between outcome and haematological toxicity during doxorubicin treatment may be useful to reassure advanced STS patients that failure to experience haematological toxicity during treatment does not equate to under-treatment.
AB - INTRODUCTION: As both anti-tumour effects and toxicity are thought to be dose-dependent, patients with the greatest toxicity may also have the best outcome. We assessed whether severity of doxorubicin-induced hematological toxicity is associated with outcome in advanced soft tissue sarcoma (STS) patients. In addition, risk factors for hematological toxicity were explored.METHODS: Worst haematological toxicities (anaemia, leukopenia, neutropenia and thrombocytopenia) seen during treatment were scored according to CTCAE toxicity score. Differences in overall survival (OS), progression free survival (PFS) and response rate (RR) between patients with or without high haematological toxicity (grades 0-2 vs. 3-4) were assessed using conventional statistical tests. Associations between baseline characteristics and hematological toxicity were established using logistic multivariate regression.RESULTS: In 557 patients eligible for this analysis, 47.2% of the patients received at least six cycles of treatment; 45% stopped treatment early due to progression, 3% because of toxicity. Relative dose intensity (RDI) was constant over the cycles. OS, PFS, and RR did not differ between patients with grade 3/4 toxicity during treatment versus those with grade 1/2. Risk factors for grade 3/4 haematological toxicity, in particular neutropenia, were age above 60 years, low BMI, and female gender.CONCLUSION: In this large series, risk factors for haematological toxicity in STS patients receiving doxorubicin monotherapy were revealed. The finding that there was no association between outcome and haematological toxicity during doxorubicin treatment may be useful to reassure advanced STS patients that failure to experience haematological toxicity during treatment does not equate to under-treatment.
KW - Adult
KW - Antibiotics, Antineoplastic/administration & dosage
KW - Bone Neoplasms/drug therapy
KW - Disease-Free Survival
KW - Doxorubicin/administration & dosage
KW - Female
KW - Hematologic Diseases/chemically induced
KW - Humans
KW - Male
KW - Middle Aged
KW - Retrospective Studies
KW - Sarcoma/drug therapy
KW - Treatment Outcome
U2 - 10.1080/0284186X.2018.1449248
DO - 10.1080/0284186X.2018.1449248
M3 - Article
C2 - 29521151
VL - 57
SP - 1117
EP - 1126
JO - Acta Oncologica
JF - Acta Oncologica
SN - 0001-6381
IS - 8
ER -