Amrubicin: potential in combination with cisplatin or carboplatin to treat small-cell lung cancer

Figures & data

Figure 1 Chemical structures of doxorubicin (A), amrubicin (B), and amrubicinol (C).

Table 1 Phase I studies of monotherapy and combination therapy with amrubicin in NSCLC and SCLC

Drug	Patients	MTD	RD	PK parameters at RD	Toxicities	Reference
Amrubicin	n = 15 (refractory relapsed lung cancer)	40 mg/m^2	35 mg/m^2	Cmax (ng/mL): 3414 ± 1744 (ARM); 170 ±119 (ARMOL) AUC (ng h/mL): 13071 ± 2931 (ARM); 2476 ± 439 (ARMOL) CL(L/h): 10.1 ±2.7 (ARM) T½ (h): 7.1 ± 1.3 (ARM); 18.0 ± 3.0 (ARMOL)	Leukopenia, neutropenia, thrombocytopenia, anemia	Okamoto et al^Citation20
Amrubicin (weekly regimen)	n = 16 (refractory relapsed lung cancer)	65 mg/m^2 (weekly dose)	60 mg/m^2 (weekly dose)	Cmax(ng/mL): 7919* (ARM); 44.8* (ARMOL) AUC (ng h/mL): 5737 ± 364 (ARM); 378 ± 182 (ARMOL) CL(L/h): 10.09 ±0.99 (ARM) T½ (h): 3.63 ± 0.67 (ARM); 13.39 ± 1.99 (ARMOL)	Leukocytopenia, neutropenia, febrile neutropenia	Kitagawa et al^Citation28
Amrubicin + cisplatin	n = 7 (with ED-SCLC, previously untreated)	Amrubicin 45 mg/m^2 + cisplatin 60 mg/m^2	Amrubicin 40 mg/m^2 + cisplatin 60 mg/m^2	Cmax (ng/mL): NR (ARM); NR (ARMOL) AUC (ng h/mL): 351 1 ± 514 (ARM); NR (ARMOL) CL(L/h): 11.6 ± 1.9 (ARM) T½ (h): 2.89 ± 0.34 (ARM); NR (ARMOL)	Neutropenia, leukopenia, febrile neutropenia, constipation	Ohe et al^Citation25
Amrubicin + carboplatin	n = 15 (with ED-SCLC)	Amrubicin 40 mg/m^2 + carboplatin AUC 5	Amrubicin 35 mg/m^2 + carboplatin AUC 5	NR	Neutropenia, leukopenia, thrombocytopenia, febrile neutropenia, and liver dysfunction	Fukuda et al^Citation30
Amrubicin + carboplatin	n = 12 (elderly, with SCLC)	Amrubicin 40 mg/m^2 + carboplatin AUC 4	Amrubicin 35 mg/m^2 + carboplatin AUC 4	NR	Neutropenia thrombocytopenia, diarrhea	Inoue et al^Citation31

Note:

* Only two patients participated in the study.

Abbreviations: ARM, amrubicin; ARMOL, Amrubicinol; AUC, area under the concentration-time curve; CL, total body clearance; C_max, maximal plasma concentration; ED, extensive disease; MTD, maximum-tolerated dose; NR, not reported; NSCLC, non-small-cell lung cancer; PK, pharmacokinetic; RD, recommended dose; SCLC, small-cell lung cancer; T_½, half-life time at terminal phase.

Table 2 Phase II studies of amrubicin monotherapy or combination therapy with a platinum agent in SCLC patients

Drug	Patients	n	ORR (%)	PFS (months)	MST (months)	Country	Reference
Monotherapy
Amrubicin	Sensitive relapse	44	52	4.2	11.6	Japan	Onoda et al^Citation33
	Refractory relapse	16	50	2.6	10.3
Amrubicin (comparator: topotecan)	Sensitive relapse	17 (19)	53 (21)	3.9 (3.0)	9.9 (11.7)	Japan	inoue et al^Citation34
	Refractory relapse	12 (11)	17 (0)	2.6 (1.5)	5.3 (5.4)
Amrubicin	Sensitive relapse	10	60	4	12	Japan	Kaira et al^Citation35
	Refractory relapse	19	36.8	4	11
Amrubicin (comparator: topotecan)	Refractory relapse	75	21.3	3.2	6	USA and EU	Ettinger et al^Citation36
Amrubicin	Sensitive relapse	50	44	4.5	9.2	USA	Jotte et al^Citation37
		(26)	(15)	(3.3)	(7.2)
Combination therapy
Amrubicin + cisplatin	with ED-SCLC, previously untreated	41	87.8	NA	13.6	Japan	Ohe et al^Citation29
Amrubicin + cisplatin	with ED-SCLC, previously untreated	33	77	6.9	11.1	EU	O’Brien et al^Citation38
Comparators
Amrubicin alone		33	61	5.2	11.1
Cisplatin etoposide		33	63	5.8	10
Amrubicin + carboplatin	Chemotherapy-naïve elderly patients with SCLC	36	89	5.8	18.6	Japan	Inoue et al^Citation31
Amrubicin + carboplatin	Previously treated patients					Japan	Hirose et al^Citation39
	Sensitive relapse	12	58.3	5	10
	Refractory relapse	13	15.4	2	5

Abbreviations: ED, extensive disease; EU, European Union; MST, median survival time; n, number; ORR, overall response rate; PFS, median progression-free survival; SCLC, small-cell lung cancer; NA, not applicable.

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