First-line chemotherapy in very elderly patients with metastatic pancreatic cancer: Gemcitabine monotherapy vs combination chemotherapy

Table 1 Baseline characteristics before propensity score matching

Variable	Elderly group: 65-74 yr			Very elderly group: 75+ yr
	Gemcitabine mono,n = 25	GA and FOLFIRINOX, n = 49	P value	Gemcitabine mono,n = 20	GA and FOLFIRINOX, n = 10	P value
Age in year	70.9 ± 3.2	69.2 ± 2.7	0.020a	77.5 (76.8-78.9)	76.5 (75.6-78.8)	0.397
Male	10 (40.0)	40 (81.6)	0.000a	14 (70.0)	7 (70.0)	0.999
Body weight in kg	54.8 ± 9.0	59.8 ± 8.8	0.026a	56.0 (43.1-62.7)	54.3 (49.1-68.3)	0.856
Height in m	1.58 ± 0.09	1.65 ± 0.08	0.001a	1.63 (1.57-1.67)	1.62 (1.56-1.69)	0.979
Body mass index in kg/m2	22.0 ± 2.7	22.1 ± 3.0	0.977	22.1 (20.7-23.5)	21.6 (19.9-24.2)	0.775
Metastasis no > 2	18 (72.0)	23 (46.9)	0.041a	13 (65.0)	4 (40.0)	0.206
Site of metastasis
Liver	18 (72.0)	30 (61.2)	0.256	12 (60.0)	3 (30.0)	0.130
Peritoneal carcinomatosis	10 (40.0)	20 (40.8)	0.574	6 (30.0)	4 (40.0)	0.599
Lung	5 (20.0)	9 (18.4)	0.548	4 (20.0)	2 (20.0)	0.999
Primary tumor site			0.671			0.467
Head	10 (40.0)	26 (53.1)		9 (45.0)	3 (30.0)
Body	10 (40.0)	11 (22.4)		5 (25.0)	3 (30.0)
Tail	5 (20.0)	12 (24.5)		6 (30.0)	4 (40.0)
Biliary stenting due to obstruction	11 (44.0)	20 (40.8)	0.796	6 (30.0)	3 (30.0)	0.999
Tumor burden	81.8 ± 43.3	61.4 ± 32.5	0.025a	81.5 (21.0-159.0)	50.0 (15.0-225.0)	0.109
ECOG performance status			0.007a			0.027a
0	5 (20.0)	22 (44.9)		2 (10.0)	4 (40.0)
1	14 (56.0)	24 (49.0)		10 (50.0)	5 (50.0)
2	6 (24.0)	3 (6.1)		8 (40.0)	1 (10.0)
Diabetes	13 (52.0)	24 (49.0)	0.809	7 (35.0)	2 (20.0)	0.416
Hypertension	10 (40.0)	18 (36.7)	0.788	9 (45.0)	2 (20.0)	0.193
Laboratory findings
White blood cell as /μL	6648.0 ± 2411.7	6793.5 ± 2606.2	0.817	8175.0 (6432.4-10546.6)	7985.0 (5824.6-9631.4)	0.880
Platelet as 103/μL	197.1 ± 68.0	244.6 ± 124.7	0.081	191.5 (168.5-217.5)	243.5 (205.1-291.3)	0.028a
N/L ratio	3.9 ± 3.0	3.4 ± 2.8	0.532	3.91 (3.23-6.49)	2.19 (1.22-4.09)	0.055
Platelet/lymphocyte ratio	159.2 ± 74.5	166.6 ± 90.9	0.724	125.6 (120.5-198.4)	136.1 (94.3-176.3)	0.559
C-related protein in mg/dL	1.9 ± 3.0	1.1 ± 1.9	0.175	1.22 (0.96-4.72)	0.75 (0.12-3.04)	0.448
Albumin in g/dL	3.6 ± 0.7	4.0 ± 0.5	0.005a	3.5 (3.2-3.8)	4.3 (3.9-4.5)	0.001a
Total bilirubin in mg/dL	0.98 ± 1.10	1.31 ± 2.10	0.464	0.49 (0.42-0.78)	0.41 (-0.03-2.14)	0.948
CA 19-9 in U/mL	3448.1 ± 8082.3	11073.9 ± 55832.2	0.501	666.4 (-2198.6-21079.9)	341.7 (-11731.7-33174.5)	0.328

Data are presented as: n (%); mean ± standard deviation; median (95% confidence interval).

^aP < 0.05. ALP: Alkaline phosphatase; CA: Carbohydrate antigen; GA: Gemcitabine plus nab-paclitaxel; N/L ratio: Neutrophil/lymphocyte ratio.

Table 2 Baseline characteristics after propensity score matching

Variable	Elderly group: 65-74 yr			Very elderly group: 75+ yr
	Gemcitabine mono, n = 25	GA and FOLFIRINOX, n = 25	P value	Gemcitabine mono, n = 10	GA and FOLFIRINOX, n = 10	P value
Age in year	70.9 ± 3.2	70.5 ± 2.6	0.626	77.0 (75.9-78.5)	76.5 (75.6-78.8)	0.853
Male	10 (40.0)	16 (64.0)	0.093	7 (70.0)	7 (70.0)	0.999
Body weight in kg	54.8 ± 9.0	59.7 ± 8.8	0.062	54.8 (49.4-65.5)	54.3 (49.1-68.3)	0.762
Height in m	1.58 ± 0.09	1.62 ± 0.09	0.060	1.64 (1.51-1.68)	1.62 (1.56-1.69)	0.696
Body mass index in kg/m2	22.0 ± 2.7	22.6 ± 2.7	0.438	22.6 (20.7-24.4)	21.6 (19.9-24.2)	0.633
Metastasis no > 2	18 (72.0)	16 (64.0)	0.554	4 (40.0)	4 (40.0)	0.999
Site of metastasis
Liver	18 (72.0)	16 (64.0)	0.554	5 (50.0)	3 (30.0)	0.388
Peritoneal carcinomatosis	10 (40.0)	7 (28.0)	0.381	3 (30.0)	4 (40.0)	0.660
Lung	5 (20.0)	7 (28.0)	0.518	0 (0)	2 (20.0)	0.151
Primary tumor site			0.603			0.464
Head	10 (40.0)	14 (56.0)		5 (50.0)	3 (30.0)
Body	10 (40.0)	5 (20.0)		2 (20.0)	3 (30.0)
Tail	5 (20.0)	6 (24.0)		3 (30.0)	4 (40.0)
Biliary stenting due to obstruction	11 (44.0)	12 (48.0)	0.782	4 (40.0)	3 (30.0)	0.660
Tumor burden	81.8 ± 43.3	68.0 ± 34.4	0.217	67.5 (44.1-98.7)	50.0 (23.5-109.9)	0.436
ECOG Performance status			0.101			0.145
0	5 (20.0)	10 (40.0)		2 (20.0)	4 (40.0)
1	14 (56.0)	12 (48.0)		4 (40.0)	5 (50.0)
2	6 (24.0)	3 (12.0)		4 (40.0)	1 (10.0)
Diabetes	13 (52.0)	15 (60.0)	0.578	5 (50.0)	2 (20.0)	0.177
Hypertension	10 (40.0)	10 (40.0)	0.999	6 (60.0)	2 (20.0)	0.074
Laboratory findings
White blood cell as /μL	6648.0 ± 2411.7	7122.4 ± 2777.8	0.522	6195.0 (4330.2-11393.8)	7985.0 (5824.6-9631.4)	0.912
Platelet as 103/μL	197.1 ± 68.0	248.7 ± 125.8	0.078	171.5 (140.7-236.5)	243.5 (205.1-291.3)	0.089
N/L ratio	3.9 ± 3.0	3.8 ± 2.9	0.937	2.32 (1.60-5.36)	2.20 (1.22-4.09)	0.684
Platelet/lymphocyte ratio	159.2 ± 74.5	172.8 ± 102.3	0.594	121.6 (93.2-165.9)	136.1 (94.3-176.3)	0.853
C-related protein in mg/dL	1.9 ± 3.0	1.7 ± 2.4	0.800	0.45 (0.18-2.00)	0.75 (0.12-3.04)	0.796
Albumin in g/dL	3.6 ± 0.7	3.8 ± 0.5	0.182	4.0 (3.7-4.1)	4.3 (3.9-4.5)	0.123
Total bilirubin in mg/dL	0.98 ± 1.10	1.7 ± 2.4	0.246	0.44 (0.30-0.63)	0.41 (-0.03-2.14)	0.684
CA 19-9 in U/mL	3448.1 ± 8082.3	5260.9 ± 20304.3	0.681	482.9 (78.7-3297.4)	341.7 (-11731.7-33174.5)	0.393

Data are presented as: n (%); Mean ± SD; Median (95% confidence interval). ALP: Alkaline phosphatase; CA: Carbohydrate antigen; N/L ratio: Neutrophil/lymphocyte ratio.

Table 3 Result of chemotherapy response of each regimen

	Elderly group: 65-74 yr			Very elderly group: 75+ yr
	Gemcitabine mono, n = 25	GA and FOLFIRINOX, n = 25	P value	Gemcitabine mono, n = 10	GA and FOLFIRINOX, n = 10	P value
Chemo response1			0.069			0.355
PR	0 (0.0)	3 (12.5)		0 (0.0)	0 (0.0)
SD	10 (67.7)	16 (66.7)		6 (60.0)	8 (80.0)
PD	7 (41.2)	5 (20.8)		4 (40.0)	2 (20.0)
DCR, PR + SD	10 (58.8)	19 (79.2)	0.166	6 (60.0)	8 (80.0)	0.355
Tumor burden change, %	11.4 ± 22.8	-4.1 ± 23.1	0.049a	7.0 (-9.1-39.7)	3.5 (-5.9-13.4)	0.633
Tumor burden change, % in patients with PR or SD	1.1 ± 7.1	-10.7 ± 19.5	0.091	-7.0 (-23.9-8.6)	0.0 (-7.7-10.0)	0.366
Dose reduction	10 (40.0)	18 (72.0)	0.022a	7 (70.0)	9 (90.0)	0.288
Delivery dose	89.6 ± 12.4	84.4 ± 15.3	0.196	81.9 (73.1-93.4)	67.7 (64.6-84.6)	0.218
Total over 80% dose	17 (68.0)	15 (60.0)	0.565	6 (60.0)	4 (40.0)	0.398
Chemotherapy days	56.0 (29.7-82.3)	112.0 (43.5-180.5)	0.001a	98.0 (0.0-206.5)	112.0 (27.0-197.0)	0.790
Progression-free survival	62.0 (55.3-125.4)	206.0 (158.1-300.5)	0.000a	147.0 (86.4-263.0)	174.0 (94.6-270.4)	0.796
Overall survival	102.0 (75.6-155.1)	302.0 (215.9-388.4)	0.000a	227.0 (108.9-342.1)	211.0 (125.3-314.3)	0.739
2nd chemotherapy	3 (12.0)	12 (48.0)	0.005a	1 (10.0)	3 (30.0)	0.288
TS-1	1 (4.0)	6 (24.0)		1 (10.0)	2 (20.0)
Gemcitabine mono	0 (0.0)	4 (16.0)		0 (0.0)	1 (10.0)
GA	0 (0.0)	1 (4.0)		0 (0.0)	0 (0.0)
FOLFIRINOX	0 (0.0)	0 (0.0)		0 (0.0)	0 (0.0)
Onivyde	1 (4.0)	0 (0.0)		0 (0.0)	0 (0.0)
5-FU base	1 (4.0)	1 (4.0)		0 (0.0)	0 (0.0)
2nd chemotherapy PFS in d	86.0 (23.7-125.6)	83.0 (45.5-123.4)	0.572	75 (N/A)	74 (-17.5-136.9)	0.999

Data presented as: n (%); Mean ± SD; Median: 95% confidence interval;

¹Includes only patients who survive over 60 d.

^aP < 0.05. 5-FU: 5-fluorouracil; DCR: Disease control rate; GA: Gemcitabine plus nab-paclitaxel; PD: Progressive disease; PFS: Progression-free survival; PR: Partial response; SD: Stable disease; TS-1: Titanium silicate-1.

Table 4 Adverse events of each regimen

Adverse events	Gemcitabine mono, n = 45	GA, n = 34	FOLFIRINOX, n = 25	P value
Admission	13 (28.9)	11 (32.4)	10 (40.0)	0.359
Thromboembolism	4 (8.9)	2 (5.9)	7 (28.0)	0.041a
Neuropathy (Grade 1,2/3,4)	0 (0.0) (0/0)	21 (61.8) (7/14)	7 (28.0) (6/1)	0.006a
Neutropenia (Grade 1,2/3,4)	18 (40.0) (9/9)	26 (76.5) (9/17)	21 (84.0) (7/14)	0.000a
Thrombocytopenia (Grade 1,2/3,4)	24 (53.3) (14/10)	16 (47.0) (10/6)	7 (28.0) (1/6)	0.241
Nausea (Grade 1,2/3,4)	12 (26.6) (11/1)	7 (21.6) (5/2)	9 (36.0) (7/2)	0.344
Fatigue (Grade 1,2/3,4)	22 (48.9) (12/10)	24 (64.7) (12/10)	16 (64.0) (9/7)	0.245
Diarrhea (Grade 1,2/3,4)	8 (17.8) (7/1)	7 (20.6) (5/2)	8 (32.0) (4/4)	0.065
Colitis/pneumonia	9 (20.0) (2/7)	7 (20.5) (1/6)	6 (24.0) (3/3)	0.959

Data are presented as: n (%).

^aP < 0.05. GA: Gemcitabine plus nab-paclitaxel

Table 5 Adverse events of each regimen according to elderly and very elderly

Adverse events	Gemcitabine mono, n = 45		GA & FOLFIRINOX, n = 59		P value
	Elderly, n = 25	Very elderly, n = 20	Elderly, n = 49	Very elderly, n = 10	Elderly	Very elderly
Admission	13 (28.9)		21 (35.6)		0.475
	6 (24.0)	7 (35.0)	18 (36.7)	3 (30.0)	0.275	0.793
Thromboembolism	4 (8.9)		9 (15.3)		0.336
	2 (8.0)	2 (10.0)	7 (14.3)	2 (20.0)	0.441	0.465
Neuropathy (Grade 1,2/3,4)	0 (0.0)		28 (47.5)		0.000*
	(0/0)		(13/15)
	0 (0.0)	0 (0.0)	23 (46.9)	5 (50.0)	0.000*	0.001a
	(0/0)	(0/0)	(9/14)	(4/1)
Neutropenia (Grade 1,2/3,4)	18 (40.0)		47 (79.7)		0.000*
	(9/9)		(16/31)
	9 (36.0)	9 (45.0)	38 (77.6)	9 (90.0)	0.000*	0.038a
	(4/5)	(5/4)	(11/27)	(5/4)
Thrombocytopenia (Grade 1,2/3,4)	24 (53.3)		23 (39.0)		0.312
	(14/10)		(11/12)
	12 (48.0) (8/4)	12 (60.0) (6/6)	19 (38.8) (9/10)	4 (40.0) (2/2)	0.806	0.370
Nausea (Grade 1,2/3,4)	12 (26.6)		16 (27.1)		0.655
	(11/1)		(12/4)
	5 (20.0)	7 (35.0)	14 (28.6)	2 (20.0)	0.236	0.354
	(5/0)	(6/1)	(10/4)	(2/0)
Fatigue (Grade 1,2/3,4)	22 (48.9)		38 (64.4)		0.171
	(12/10)		(21/17)
	11 (44.0)	11 (55.0)	32 (65.3)	6 (60.0)	0.101	0.669
	(7/4)	(5/6)	(19/13)	(2/4)
Diarrhea (Grade 1,2/3,4)	8 (17.8)		15 (25.4)		0.180
	(7/1)		(9/6)
	5 (20.0)	3 (15.0)	12 (24.5)	3 (30.0)	0.635	0.074
	(4/1)	(3/0)	(9/3)	(0/3)
Colitis/pneumonia	9 (20.0)		13 (22.0)		0.906
	(2/7)		(4/9)
	3 (12.0)	6 (30.0)	12 (24.5)	1 (10.0)	0.205	0.134
	(1/2)	(1/5)	(3/9)	(1/0)

Data are presented as: n (%).

^aP < 0.05. GA: Gemcitabine plus nab-paclitaxel.