Eribulin, Child-Pugh score, and liver-function tests: lessons from pivotal breast cancer studies 301 and 305

Macpherson, Iain R.; He, Yaohua; Palmieri, Carlo

doi:10.1186/s13058-021-01407-w

Breast Cancer Research

Table 4 Proposed Macpherson-Palmieri dosing scheme for eribulin mesylate

From: Eribulin, Child-Pugh score, and liver-function tests: lessons from pivotal breast cancer studies 301 and 305

*Initial dosing*
	Clinical definition	Dosing recommendations
Group 1	Adequate liver function^a	1.4 mg/m² (equivalent to 1.23 mg/m² eribulin [expressed as free base])
Group 2	Bilirubin level: > ULN ≤ 1.5 × ULN	1.1 mg/m²
Group 3	Bilirubin level: > 1.5 × ULN or ALT/AST: ≥ 3 × ULN (for liver metastases, ALT/AST: ≥ 5 × ULN)	0.7 mg/m^{2 b}
*Subsequent dosing: day 8*
	Clinical finding	Dosing modification
Group 1	ANC < 1.0 × 10⁹/L and/or platelet count < 75 × 10⁹/L; or nonhematological AE > grade 2^c	Postpone treatment until recovery
Group 2	ANC < 1.0 × 10⁹/L and/or platelet count < 75 × 10⁹/L; or nonhematological AE > grade 2^c	Postpone treatment until recovery
Group 3	ANC < 1.0 × 10⁹/L and/or platelet count < 75 × 10⁹/L; or nonhematological AE > grade 2^c	Postpone treatment; omit day 8
*Recovery on day 15 or earlier*
	Clinical action	Dosing modification
Group 1	Resume treatment on the day that recovery is observed (considered new day 8 of cycle)	1.1 mg/m²
Group 2	Resume treatment on the day that recovery is observed (considered new day 8 of cycle)	0.7 mg/m²
*Recovery after day 15*
	Clinical action	Dosing modification
Group 1	Omit day 8 and resume scheduled treatment on day 1 of next cycle	1.1 mg/m²
Group 2	Omit day 8 and resume scheduled treatment on day 1 of next cycle	0.7 mg/m²
Special considerations:
• Grade 4 neutropenia > 7 days
• Grade 3/4 neutropenia with fever or infection requiring treatment with growth factors and/or antibiotics
• Grade 4 thrombocytopenia
• Grade 3 thrombocytopenia requiring platelet and/or blood transfusion
• Nonhematologic grade 3–4 toxicities
	Clinical action	Dosing modification
Group 1	Resume treatment on day 1 of next cycle	1.1 mg/m²
Group 2	Resume treatment on day 1 of next cycle	0.7 mg/m²
Group 3		Consider stopping treatment with eribulin mesylate
Dose escalation^d
	Clinical action	Dose modification
Group 2 and 3	If, following cycle 1 day 1 and cycle 1 day 8, there are no toxicity issues (especially hematological toxicities determined by ANC and platelets), consider increasing dose at the start of the next cycle Refer to day 8 of this table to assess hematological and nonhematological toxicities at the next dose level; reduce dose if necessary	Next dose level

This dosing scheme is the work of investigators (IM and CP). These unproven recommendations require further study; dosing recommendations are based on eribulin mesylate unless otherwise specified
^aDefined as bilirubin ≤ ULN and AP, ALT, and AST ≤ 3 × ULN (in the presence of liver metastases: ≤ 5 × ULN); unless there are bone metastases, in which case liver-specific AP must be separated from the total and used to assess the liver function instead of the total AP. If AP is > 3 × ULN (in absence of liver metastases) or > 5 × ULN (in presence of liver metastases) and patient also is known to have bone metastases, the liver-specific AP must be separated from the total and used to assess the liver function instead of the total AP
^bThere are no data for this group given that such patients were excluded from the study. Given the lack of clinical data, extreme caution should be applied to the use of eribulin within this group and clinical judgment should be used. If eribulin is used, then close monitoring for toxicities is required
^cExcept inadequately treated nausea and/or vomiting
^dTo be considered when treatment was initiated at a lower starting dose
AE, adverse event; ALT, alanine transaminase; ANC, absolute neutrophil count; AP, alkaline phosphatase; AST, aspartate transaminase; ULN, upper limit of normal

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ISSN: 1465-542X

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