Effects of chemotherapy dose intensity on short-term efficacy in patients with advanced colon cancer： a study based on real-world data

doi:10.3760/cma.j.cn371439-20220318-00078

Abstract

Abstract:

Objective To investigate the effects of different chemotherapy dose intensity on the short-term efficacy and adverse reactions of patients with advanced colon cancer. Methods A real-world database of patients with advanced colon cancer in Wangjing Hospital of China Academy of Chinese Medical Sciences and China-Japan Friendship Hospital from January 2017 to December 2020 was established, including 105 patients treated with the same chemotherapy regimen for two consecutive cycles. The patients were grouped according to the average relative dose intensity （ARDI） of chemotherapy, and the population differences, treatment regimens, short-term efficacy and adverse reactions of different chemotherapy dose intensities were evaluated. The receiver operating characteristic （ROC） curve was used to analyze the predictive value of ARDI for short-term efficacy. Results There were 31 patients in the high dose intensity group （ARDI≥80%）, 34 patients in the medium dose intensity group （80%<ARDI<60%）, and 40 patients in the low dose intensity group （ARDI≤60%）. There were statistically significant differences in age （χ²=13.20, P=0.010） and Karnofsky functional status （KPS） score （χ²=7.99, P=0.008） among the high dose intensity group, medium dose intensity group and low dose intensity group. Compared with the low dose intensity group, the proportion of young and middle-aged patients in the high dose intensity group was higher, and the proportion of elderly patients was lower （χ²=12.63, P=0.002）. Compared with the medium dose intensity group, the proportion of patients with KPS score ≥60 was lower and the proportion of patients with KPS score <60 was higher in the low dose intensity group （P=0.013）. There was a statistically significant difference in the application of chemotherapy regimen among the three groups （χ²=22.88, P=0.027）, and there was a statistically significant difference in the application of chemotherapy regimen between the high dose intensity group and low dose intensity group （χ²=16.25, P=0.009）. The proportions of the high, medium and low dose intensity groups receiving combined chemotherapy were 96.77% （30/31）, 82.35% （28/34） and 80.00% （32/40） respectively. The incidences of chemotherapy drug reduction in the high, medium and low dose intensity groups were 93.55% （29/31）, 100% （34/34） and 100% （40/40） respectively, and the incidences of chemotherapy delay were 41.94% （13/31）, 79.41% （27/34） and 87.50% （35/40） respectively. The objective response rates of the high, medium and low dose intensity groups were 22.58% （7/31）, 14.71% （5/34） and 2.50% （1/40） respectively, with a statistically significant difference （χ²=7.11, P=0.027）. The disease control rates of the high, medium and low dose intensity groups were 93.55% （29/31）, 91.18% （31/34） and 87.50% （35/40） respectively, with no statistically significant difference （χ²=0.75, P=0.714）. The differences of carcinoembryonic antigen before and after treatment in the high, medium and low dose intensity groups were 2.09, 0.47 and -0.72 ng/ml respectively, with a statistically significant difference （χ²=10.09, P=0.006）. Compared with the low dose intensity group, the difference of carcinoembryonic antigen before and after treatment in the high dose intensity group was greater （χ²=23.12, P=0.005）. The differences of carbohydrate antigen 199 before and after treatment in the high, medium and low dose intensity groups were 2.30, 0.00 and -0.21 U/ml respectively, with a statistically significant different （χ²=8.85, P=0.012）. Compared with the low dose intensity group, the difference of carbohydrate antigen 199 before and after treatment in the high dose intensity group was greater （χ²=21.40, P=0.010）. No adverse reactions above grade 3 occurred in the three groups, and the safety was good. The most common adverse reactions were anemia （61.90%, 65/105）, leucopenia （39.05%, 41/105）, neutropenia （29.52%, 31/105） and nausea （36.19%, 38/105）. There were no statistically significant differences in the incidences of adverse reactions among the high, medium and low dose intensity groups （all P>0.05）. ROC curve analysis found that the area under the curve predicting objective response was 0.70, the sensitivity was 92.30%, and the specificity was 52.10% when the chemotherapy ARDI threshold was 64%. Conclusion In the real world, colon cancer patients receiving high dose intensive chemotherapy have better objective response rate,and tumor markers decreased significantly. The baseline status of colon cancer patients receiving low dose intensive chemotherapy is poor, but there is no statistically significant difference in disease control rate between patients receiving low dose intensive chemotherapy and patients receiving high dose intensive chemotherapy, and the adverse reactions are controllable.

Key words: Colonic neoplasms, Drug therapy, Dosimetry, Efficacy evaluation, Adverse effects

Chu Xuelei, Mao Yun, Xue Peng, Li Linlu, Chen Meichi, Yuan Chunsheng, Qin Xiaoyan, Zhu Shijie. Effects of chemotherapy dose intensity on short-term efficacy in patients with advanced colon cancer： a study based on real-world data[J]. Journal of International Oncology, 2022, 49(7): 408-415.

Figures/Tables 8

References 25

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临床特征	高剂量强度组（n=31）	中剂量强度组（n=34）	低剂量强度组（n=40）	χ²值	P值
性别
男	20（64.52）	19（55.88）	21（52.50）	1.06	0.588
女	11（35.48）	15（44.12）	19（47.50）	1.06	0.588
年龄（岁）
<60	12（38.71）^a	7（20.59）	7（17.50）	13.20	0.010
60~74	18（58.06）	19（55.88）	18（45.00）
≥75	1（3.23）	8（23.53）	15（37.50）
KPS评分（分）
≥60	30（96.77）	34（100）^a	33（82.50）	7.99	0.008
<60	1（3.23）	0（0）	7（17.50）	7.99	0.008
BMI
<18.5	4（12.90）	3（8.82）	3（7.50）	4.95	0.283
18.5≤BMI<25	20（64.52）	22（64.71）	19（47.50）
25≤BMI<30	7（22.58）	7（20.59）	18（45.00）
≥30	0（0）	2（5.88）	0（0）
既往史
糖尿病	10（32.26）	7（20.59）	12（30.00）	12.93	0.107
心血管疾病	12（38.71）	18（52.94）	20（50.00）
脑血管疾病	2（6.45）	3（8.82）	12（30.00）
消化道疾病	4（12.90）	6（17.65）	2（5.00）
既往体健	15（48.39）	9（26.47）	13（32.50）
原发部位
左半结肠	19（61.29）	19（55.88）	17（42.50）	2.72	0.257
右半结肠	12（38.71）	15（44.12）	23（57.50）	2.72	0.257
转移部位
肝	24（77.42）	25（73.53）	26（65.00）	4.22	0.655
肺	8（25.81）	9（26.47）	14（35.00）
骨	5（16.13）	1（2.94）	4（10.00）
其他	11（35.48）	11（32.35）	18（45.00）
转移数量（个）
≤1	17（54.84）	22（64.71）	22（55.00）	0.90	0.637
>1	14（45.16）	12（35.29）	18（45.00）	0.90	0.637

化疗方案	高剂量强度组（n=31）	中剂量强度组（n=34）	低剂量强度组（n=40）
FOLFOXIRI	3（9.68）^a	1（2.94）	7（17.50）
CapeOx	5（16.13）	11（32.35）	11（27.50）
mFOLFOX6	17（54.84）	10（29.41）	6（15.00）
FOLFIRI	2（6.45）	3（8.82）	6（15.00）
mXELIRI	2（6.45）	3（8.82）	2（5.00）
CapIRI	1（3.23）	0（0）	0（0）
5-FU/LV	0（0）	0（0）	1（2.50）
Cap	1（3.23）	6（17.65）	7（17.50）
χ²值	22.88
P值	0.027

化疗方案	药物	高剂量强度组（n=31）	中剂量强度组（n=34）	低剂量强度组（n=40）
FOLFOXIRI	伊立替康	77.00±6.25	57.00^a	38.29±12.05
	奥沙利铂	102.67±9.07	83.00^a	53.71±10.19
	氟尿嘧啶	66.00±5.29	51.00^a	33.57±6.71
CapeOx	奥沙利铂	81.00±4.90	66.64±11.50	46.91±12.22
	卡培他滨	94.20±9.55	69.73±7.39	55.36±10.39
mFOLFOX6	奥沙利铂	94.06±11.00	73.60±12.24	61.17±7.94
	氟尿嘧啶	87.59±6.60	62.80±12.80	35.67±8.64
FOLFIRI	伊立替康	81.50±4.95	63.33±3.51	44.17±13.82
	氟尿嘧啶	86.00±2.83	63.33±4.04	47.33±5.43
mXELIRI	伊立替康	86.00±9.90	44.33±12.10	24.50±2.12
	卡培他滨	92.50±7.78	98.00±8.89	74.00±18.39
CapIRI	伊立替康	76.00^a	—	—
	卡培他滨	105.00^a	—	—
5-FU/LV	氟尿嘧啶	—	—	47.00^a
Cap	卡培他滨	86.00^a	67.50±5.47	44.29±5.74

组别	CR	PR	SD	PD	疾病控制	客观缓解
高剂量强度组（n=31）	0（0）	7（22.58）	22（70.97）	2（6.45）	29（93.55）	7（22.58）
中剂量强度组（n=34）	0（0）	5（14.71）	26（76.47）	3（8.82）	31（91.18）	5（14.71）
低剂量强度组（n=40）	0（0）	1（2.50）	34（85.00）	5（12.50）	35（87.50）	1（2.50）
χ²值					0.75	7.11
P值					0.714	0.027

组别	CEA（ng/ml）	CA199（U/ml）
高剂量强度组（n=31）	2.09（34.99）^a	2.30（69.50）^a
中剂量强度组（n=34）	0.47（31.65）	0.00（18.46）
低剂量强度组（n=40）	-0.72（14.08）	-0.21（8.81）
χ²值	10.09	8.85
P值	0.006	0.012