Safety of Endostar in combination with chemotherapy in patients with cancer

doi:10.21203/rs.3.rs-36626/v1

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Safety of Endostar in combination with chemotherapy in patients with cancer

https://doi.org/10.21203/rs.3.rs-36626/v1

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Background: A number of studies indicated the benefits and safety of Endostar in combination with chemotherapy in cancer, but the exact real-life safety of Endostar is poorly known. This study aimed to assess the safety of Endostar in combination with chemotherapy in patients with cancer in a real-life setting in China.

Methods: This was a retrospective study of patients treated with Endostarin combination with chemotherapy in the Chinese PLA General Hospital (Beijing, China) from 1 st January 2006to 31 st December 2017. All data were obtained from the Hospital Information System(HIS). Laboratory abnormalities were evaluated according to Common Terminology Criteria for Adverse Events(CTCAE) 4.0.Bleeding events and wound healing complications after surgery associated with Endostar were evaluated based on case records.

Results: A total of 825 patients were included. There were no patients used Endostar alone in real-life settings. Overall, anemia occurred in 74.5% of the assessed patients, thrombocytopenia occurred in 29.0%, abnormal white blood cell count occurred in 54.5%, abnormal liver function occurred in 13.8%, and increased creatinine occurred in 1.2%. No definite bleeding events and wound healing complications after surgery associated with Endostar were found based on case records. Most laboratory AEs were of grade 1-2. Lung cancer, osteosarcoma and doxorubicin-based chemotherapy was associated with an increased risk of grade≥3 abnormal white blood cell count ( P <0.05). The total dose of Endostar was not associated with severe AEs(grade≥3)of thrombocytopenia and abnormal white blood cell count.

Conclusion: The occurrence of AEs during treatment with Endostar in combination with chemotherapy differed across different tumor types and chemotherapy regimens. No new unexpected AEs relating to Endostar were observed from this study. The total dose of Endostar was not associated with increased risk of severe AEs (grade≥3)of thrombocytopenia and abnormal white blood cell count when used in combination with chemotherapy in the real-life setting.

Oncology

lung cancer

liver cancer

osteosarcoma

Endostar

adverse events

Table 1. Characteristics of all patients who received at least one dose of Endostar during the study period and of the patients with available blood test data.

Variable	n=825
Age (years), median (interquartile range)	50 (28, 59)
Sex, male, n (%)	595 (72.1)
Cancer type, n (%)
Liver	151 (18.3)
Lung	190 (23.0)
Osteosarcoma	162 (19.6)
Others	322 (39.0)
Metastasis, n (%)	295 (35.8)
Mono-chemotherapy, n (%)	188 (22.8)
Platinum-based	136 (16.5)
Doublet-chemotherapy, n (%)	393 (47.6)
Platinum-based	257 (31.2)
Doxorubicin-based	132 (16.0)
Number of Endostar cycles, n (%)
1	87 (10.5)
2	226 (27.4)
>2	512 (62.1)
Total dose of Endostar, n (%)
≤ 210 mg	241 (29.2)
＞210 mg	584 (70.8)
Method of administration of Endostar, n (%)
Drip	583 (70.7)
Pump	51 (6.2)
Drip+Pump	17 (2.1)
In transcatheter arterial chemoembolization (TAE)	154 (18.7)
Thoracic injection	11 (1.3)
Peritoneal injection	8 (1.0)
Hypodermic injection	1 (0.1)

Table 2.Laboratory adverse events during treatment with Endostarand chemotherapy

	Assessed n	Any AE n, (%)	Grade 1-2 n, (%)	Grade ≥3 n, (%)
Anemia	560	417 (74.5)	360 (64.3)	57 (10.2)
Thrombocytopenia	765	222 (29.0)	147 (19.2)	75 (9.8)
Abnormal WBC count	765	417 (54.5)	242 (31.6)	175 (22.9)
Decreased WBC	765	403 (52.7)	243 (31.8)	160 (20.9)
Neutropenia	762	299 (39.2)	179 (23.5)	120 (15.8)
Abnormal liver function	246	34 (13.8)	32 (13.0)	2 (0.8)
Increased ALT	246	29 (11.8)	28 (11.4)	1 (0.4)
Increased AST	246	13 (5.3)	13 (5.3)	0
Increased bilirubin	246	6 (2.4)	5 (2)	1 (0.4)
Increased creatinine	246	3 (1.2)	3 (1.2)	0

No grade 5 AE occurred in the present study. AE: adverse event; WBC: white blood cells; ALT: alanine aminotransferase; AST: aspartateaminotransferase.

Table 3. Factors associated with severe (grade ≥3) thrombocytopenia and abnormal white blood cell count in all patients

	Thrombocytopenia			Abnormal white blood cell count
	HR	95%CI	P	HR	95%CI	P
Age (years)
<18	1	Reference		1	Reference
18-65	1.343	(0.652, 2.766)	0.423	1.018	(0.659, 1.573)	0.936
>65	1.256	(0.613, 2.571)	0.534	1.024	(0.583, 1.797)	0.935
Sex
Male	1	Reference		1	Reference
Female	1.308	(0.794, 2.156)	0.292	1.124	(0.818, 1.542)	0.471
Cancer type
Liver	1	Reference		1	Reference
Lung	0.667	(0.138, 3.235)	0.616	5.604	(2.327, 13.494)	<0.001
Osteosarcoma	1.018	(0.199, 5.198)	0.983	10.047	(4.062, 24.851)	<0.001
Others	0.668	(0.146, 3.059)	0.603	6.370	(2.787, 14.558)	<0.001
Chemotherapy
Platinum-based	1	Reference		1	Reference
Doxorubicin-based	0.879	(0.397, 1.944)	0.749	1.621	(1.018, 2.582)	0.042
Others	0.161	(0.022, 1.189)	0.073	1.269	(0.710, 2.269)	0.421
Total Endostar dose
≤210 mg	1	Reference		1	Reference
>210 mg	0.979	(0.221, 4.334)	0.978	0.591	(0.307, 1.140)	0.117

HR: hazard ratio.

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Safety of Endostar in combination with chemotherapy in patients with cancer

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