Safety and efficacy of amrubicin monotherapy in patients with platinum-refractory metastatic neuroendocrine carcinoma of the gastrointestinal tract: a single cancer center retrospective study

Figures & data

Table 1 Baseline patient characteristics (N=16)

Characteristics	N (%)
Age at enrollment in years, median (range)	65 (60–75)
Sex
Male	14 (87.5%)
Female	2 (12.5%)
ECOG PS
0	15 (93.8%)
1	1 (6.2%)
Site of primary lesion
Esophagus	3 (18.8%)
Stomach	10 (62.5%)
Duodenum	1 (6.2%)
Colorectum	2 (12.5%)
Histological type
NEC	16 (100%)
Metastatic site
Liver	11 (68.8%)
Lymph nodes	8 (50.0%)
Lung	2 (12.5%)
Other	2 (12.5%)
Number of previous chemotherapy regimens
1	14 (87.5%)
≦2	2 (12.5%)
First-line chemotherapy regimens
CDDP + irinotecan	13 (81.4%)
CDDP + ETP	1 (6.2%)
CDDP + capecitabine	1 (6.2%)
Oxaliplatin + S-1	1 (6.2%)
Starting dose of AMR (mg/m^2/day)
45	1 (6.2%)
40	11 (68.8%)
35	2 (12.5%)
30	2 (12.5%)
No. of cycles, median (range)	3 (1–15)

Abbreviations: ECOG PS, Eastern Cooperative Oncology Group Performance Status; NEC, neuroendocrine carcinoma; CDDP, cisplatin; ETP, etoposide; AMR, amrubicin; S-1, tegafur/gimeracil/oteracil. 

Table 2 Efficacy of AMR monotherapy

	N (%)
Objective response rate
Complete response	0 (0%)
Partial response	1 (6.2%)
Stable disease	6 (37.6%)
Progressive disease	8 (50.0%)
Not evaluated	1 (6.2%)
Overall response rate (%)	6.3 (95% CI: 0.2–30.2)
Disease control rate (%)	43.8 (95% CI: 19.8–70.1)

Abbreviations: AMR, amrubicin; CI, confidence interval.

Table 3 Subsequent chemotherapy after AMR monotherapy

	N (%)
Chemotherapy after AMR
Yes	10 (62.5%)
No	6 (37.5%)
Chemotherapy regimen after AMR
PAC+RAM	4 (40%)
PAC	2 (20%)
DOC	1 (10%)
FOLFOX+Bev	1 (10%)
CPT-11	1 (10%)
Other	3 (30%)
Median OS (months)
Subsequent chemotherapy	17.3 (95% CI: 5.9-NA)
Best supportive care	8.9 (95% CI: 1.1-NA)

Abbreviations: PAC, paclitaxel; RAM, ramucirumab; DOC, docetaxel; FOLFOX, fluorouracil, leucovorin and oxaliplatin; Bev, bevacizumab; CPT-11, irinotecan; OS, overall survival; AMR, amrubicin.

Table 4 Grade 3 or higher treatment-related toxicities

Toxicity	N (%)
Hematotoxicity
Neutropenia	8 (50.0)
Anemia	0 (0)
Nonhematologic toxicity
Febrile neutropenia	1 (6.2)

Figure 1 (A) Progression-free survival and (B) overall survival in all patients after first-line chemotherapy.

Abbreviations: PFS, progression free survival; OS, overall survival.

Figure 2 Overall survival of patients who received subsequent chemotherapy after amrubicin or supportive care only.

Abbreviations: OS, overall survival; NA, not applicable.

Table 5 Patient characteristics and adverse events with AMR monotherapy in previous reports

	Asayama et al^Citation4	Ando et al^Citation9	Nio et al^Citation10	Araki et al^Citation11
N (%)	N (%)	N (%)	N (%)
Number of patients	5	10	13	19
Age (years), median (range)	60 (60–70)	62 (52–78)	64 (50–76)	63 (39–81)
Sex
Female	1 (20.0)	2 (20.0)	3 (23.1)	15 (78.9)
Male	4 (80.0)	8 (80.0)	10 (76.9)	4 (21.1)
ECOG PS
0–1	3 (60.0)	6 (60.0)	12 (92.3)	18 (94.7)
2	2 (40.0)	4 (40.0)	1 (7.7)	1 (5.3)
Site of primary lesion
Esophagus	3 (60.0)	2 (20.0)	2 (15.4)	8 (42.1)
Stomach	0 (0)	5 (50.0)	6 (46.2)	4 (21.1)
Intestine	0 (0)	1 (10.0)	0 (0)	0 (0)
Colorectum	2 (40.0)	1 (10.0)	3 (23.1)	5 (26.3)
Other	0 (0)	1 (10.0)	2 (15.4)	2 (10.5)
Site of metastasis
Lymph nodes	4 (80.0)	9 (90.0)	11 (84.6)	15 (78.9)
Lung	2 (40.0)	0 (0)	4 (30.8)	4 (21.1)
Liver	1 (20.0)	6 (60.0)	9 (69.2)	15 (78.9)
Peritoneum	1 (20.0)	1 (10.0)	4 (30.8)	0 (0)
Bone	1 (20.0)	0 (0)	2 (15.4)	2 (10.5)
Other	1 (20.0)	0 (0)	6 (46.2)	0 (0)
Prior chemotherapy regimen
CDDP-based	5 (100)	9 (90.0)	12 (92.3)	18 (94.7)
CBDCA-based	0 (0)	1 (10.0)	2 (15.4)	1 (5.3)
Others	0 (0)	0 (0)	0 (0)	0 (0)
Hematotoxicity
Leukopenia	4 (80.0)	2 (20.0)	10 (76.9)	7 (36.8)
Neutropenia	4 (80.0)	4 (40.0)	11 (84.6)	10 (52.6)
Thrombocytopenia	1 (20.0)	0 (0)	4 (30.8)	1 (5.3)
Anemia	3 (60.0)	5 (50.0)	4 (30.8)	4 (21.1)
Nonhematologic toxicity
Febrile neutropenia	1 (20.0)	0 (0)	4 (30.8)	2 (10.5)
Others	0 (0)	3 (30.0)	3 (23.1)	0 (0)
Median PFS (months)	5.4	2.6	3.6	3.8
Median OS (months)	7.2	5.0	7.2	7.7

Abbreviations: CBDCA, Carboplatin; PFS, progression-free survival; AMR, amrubicin; OS, overall survival; CDDP, cisplatin ECOG PS, Eastern Cooperative Oncology Group Performance Status.

Asayama M, Fuse N, Yoshino T, et al. Amrubicin for the treatment of neuroendocrine carcinoma of the gastrointestinal tract: a retrospective analysis of five cases. Cancer Chemother Pharmacol. 2011;68(5):1325–1330. doi:10.1007/s00280-011-1619-721461890

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