Nimotuzumab combined with concurrent chemoradiotherapy benefits patients with advanced nasopharyngeal carcinoma

Figures & data

Figure 1 Flow diagram of studies selection process.

Table 1 Characteristics of included study comparing nimotuzumab combined with three-dimensional radiotherapy for nasopharyngeal carcinoma

Author	Year of publication	Age (T/C)	Sex (M/F)	Sample size (T/C)	Clinical setting	Stage	Treatment		Outcomes (within 1 year)
							Trial	Control
Li^Citation28	2016	56.9/56.5	29/19	24/24	Expected lifetime >6 months; KPS ≧60; no severe heart, lung, liver, or renal diseases; no metastasis	III–IVa	IMRT: 70–80 Gy (lesion); cisplatin: 60 mg/m^2; paclitaxel: 175 mg/m^2; nimotuzumab: 100 mg/250 mL saline, once a week for 8 weeks before radiation	IMRT: 60–80 Gy; cisplatin: 60 mg/m^2; paclitaxel: 175 mg/m^2	CR, PR, SD, PD, adverse reactions
Hu et al^Citation31	2013	49.3/49.2	40/28	36/32	Expected lifetime >6 months; no severe heart, lung, liver, or renal diseases	III–IVa	IMRT: 70–80 Gy (lesion); cisplatin: 80 mg/m^2; docetaxel: 70 mg/m^2; nimotuzumab: 100 mg/250 mL saline, once a week	IMRT: 70–80 Gy (lesion); cisplatin: 80 mg/m^2; docetaxel: 70 mg/m^2	CR, PR, SD, PD, adverse reactions
He et al^Citation32	2013	−/−	27/27	20/20	Expected lifetime >6 months; KPS ≧70; no severe infection or hemorrhagic, endocrine, heart, lung, liver, or renal diseases; no metastasis	III–IVa	IMRT: 70–76 Gy (lesion); carboplatin: 300 mg/m^2; 5-fluorouracil: 500 mg/m^2; nimotuzumab: 100 mg/250 mL saline, once a week for 6–8 weeks	IMRT: 70–76 Gy (lesion); carboplatin: 300 mg/m^2; 5-fluorouracil: 500 mg/m^2	CR, PR, SD, PD, adverse reactions
Chen et al^Citation34	2016	45.6/44.9	37/29	33/33	Expected lifetime >6 months; KPS ≧800; no metastasis; no severe heart, lung, liver, or renal diseases	III–IVa	IMRT: 60–78 Gy; cisplatin: 60 mg/m^2; 5-fluorouracil: 500 mg/m^2; calcium foliate: 200 mg/m^2; nimotuzumab: 100 mg/250 mL saline, once a week for 6–7 weeks	IMRT: 60–78 Gy; cisplatin: 60 mg/m^2; 5-fluorouracil: 500 mg/m^2; calcium foliate: 200 mg/m^2	CR, PR, SD, PD, median survival time, adverse reactions
Lu et al^Citation26	2014	39.2/39.3	28/26	27/27	KPS ≧80, no metastasis	III–IVa	IMRT: 60–70 Gy (lesion); cisplatin: 40 mg/m^2; nimotuzumab: 100 mg/250 mL saline, once a week for 8 weeks	IMRT: 60–70 Gy (lesion); cisplatin: 40 mg/m^2	CR, PR, SD, PD, adverse reactions
Cheng et al^Citation33	2016	49.8/50.6	50/30	40/40	Expected lifetime >6 months; KPS ≧70; no severe infection or hemorrhagic, endocrine, heart, brain, liver, or renal diseases; no metastasis	III–IV	3D-CRT: 70–75 Gy (lesion); cisplatin: 20 mg/m^2; paclitaxel: 175 mg/m^2; nimotuzumab: 100 mg/250 mL saline for 7 weeks	3D-CRT: 70–75 Gy (lesion); cisplatin: 20 mg/m^2; paclitaxel: 175 mg/m^2	CR, PR, SD, PD, adverse reactions
Tu^Citation4	2013	−/−	19/12	14/17	Expected lifetime >6 months; no severe infection, or hemorrhagic, endocrine, heart, brain, liver, or renal diseases; no metastasis; PS: 0–1	III–IV	IMRT: 68–72 Gy (lesion); cisplatin: 20 mg/m^2; nimotuzumab: 100 mg/250 mL saline for 6 weeks	IMRT: 68–72 Gy (lesion); cisplatin: 20 mg/m^2	CR, PR, SD, PD, adverse reactions
Yu et al^Citation23	2014	−/−	29/15	20/24	Expected lifetime >6 months; PS: 0–1; no liver, renal, or heart diseases; no metastasis	III–IV	IMRT: 66–70 Gy; cisplatin: 20 mg/m^2; nimotuzumab: 100 mg/250 mL saline for 6 weeks	IMRT: 66–70 Gy; cisplatin: 20 mg/m^2	CR, PR, SD, PD, adverse reactions
Tang et al^Citation24	2012	54.2/55.2	79/44	63/60	Expected lifetime >6 months; KPS ≧60; no metastasis; no serious organic disease	III–IVa	IMRT: 70–76 Gy; cisplatin: 60 mg/m^2; paclitaxel: 175 mg/m^2; nimotuzumab: 100 mg/250 mL saline	IMRT: 70–76 Gy; cisplatin: 60 mg/m^2; paclitaxel: 175 mg/m^2	CR, PR, SD, PD, adverse reaction
Zhou and Liao^Citation22	2013	−/−	−/−	16/16	No metastasis; no serious organic disease	III–IVa	IMRT: 60–70 Gy; cisplatin: 60 mg/m^2; nimotuzumab: 100 mg/250 mL	IMRT: 70–76 Gy; cisplatin: 60 mg/m^2	CR, PR, SD, PD, adverse reactions
Shao et al^Citation25	2014	47/50	35/13	24/24	Expected lifetime >6 months; KPS ≧70; no metastasis; no serious organic disease		IMRT: 72–76 Gy; nedaplatin; nimotuzumab: 100 mg/250 mL	IMRT: 72–76 Gy; nedaplatin	CR, PR, SD, PD, adverse reactions
Li et al^Citation30	2015	57.3/54.6	38/22	30/30	Expected lifetime >6 months; KPS ≧70; no liver, renal, or heart diseases	III–IVb	IMRT: 60–70 Gy; nedaplatin: 40 mg/500 mL saline; nimotuzumab: 100 mg/250 mL	IMRT: 60–70 Gy; nedaplatin: 40 mg/500 mL saline	CR, PR, SD, PD, adverse reactions
Lou et al^Citation27	2016	−/−	−/−	161/22	Expected lifetime >6 months; KPS ≧60; no liver, renal, or heart diseases	III–IV	IMRT: 60–70 Gy; nedaplatin: 40 mg/m^2; paclitaxel: 135 mg/m^2; nimotuzumab: 100 mg/250 mL	IMRT: 60–70 Gy; nedaplatin: 40 mg/m^2; paclitaxel: 135 mg/m^2	CR, PR, SD, PD, adverse reactions
Zhuang et al^Citation21	2016	65.8	37/5	18/15	Expected lifetime >6 months; KPS ≧60	III–IVa	IMRT: 72–80 Gy; cisplatin: 30 mg/m^2; 5-fluorouracil: 500 mg/m^2; nimotuzumab: 100 mg/250 mL	IMRT: 72–80 Gy; cisplatin: 30 mg/m^2; 5-fluorouracil: 500 mg/m^2	CR, PR, SD, PD, adverse reactions
Li et al^Citation29	2016	−/−	78/26	52/52	Expected lifetime >6 months; KPS ≧60	III–IVa	IMRT: 70–74 Gy; cisplatin: 25 mg/m^2; nimotuzumab: 200 mg/250 mL; 5-fluorouracil: 600 mg/m^2	IMRT: 70 or 74 Gy; cisplatin: 30 mg/m^2; 5-fluorouracil: 600 mg/m^2	CR, PR, SD, PD, adverse reactions

Abbreviations: KPS, Karnofsky Performance Scale; IMRT, intensity-modulated radiation therapy; CR, complete response; PR, partial disease; SD, stable disease; PD, progressive disease; 3D-CRT, three-dimensional conformal radiotherapy; PS, performance status.

Table 2 Methodological quality assessment (risk of bias) of included studies by Newcastle–Ottawa Scale

Study	Selection				Comparability	Outcome			Total score
	Exposed cohort	Nonexposed cohort	Ascertainment of exposure	Outcome of interest		Assessment of outcome	Length of follow-up	Adequacy of follow-up
Li et al^Citation29	*	*	*	*	**	*	–	–	7
Chen et al^Citation34	*	*	*	*	*	*	–	–	6
Lu et al^Citation26	*	*	*	*	**	*	–	–	7
Li et al^Citation30	*	*	*	*	**	*	–	–	7
Lou et al^Citation27	*	*	*	*	**	*	*	–	8
Li^Citation28	*	*	*	*	*	*	–	–	6

Note:

* 1 point;

** 2 points.

Figure 2 Forest plot of nimotuzumab combined with concurrent chemoradiotherapy versus chemoradiotherapy alone in advanced NPC.

Abbreviations: NPC, nasopharyngeal carcinoma; IV, inverse variance; CI, confidence interval.

Figure 3 Forest plot of adverse reactions between nimotuzumab group and chemoradiotherapy alone.

Abbreviations: IV, inverse variance; CI, confidence interval.

Figure 4 Forest plot of adverse reactions between nimotuzumab group and chemoradiotherapy alone.

Figure 5 Sensitivity analysis of the pooled estimation.

Abbreviations: IV, inverse variance; CI, confidence interval.

Figure 6 Deek’s funnel plot to evaluate the publication bias.

Abbreviation: s.e., standard error.

Figure S1 PRISMA checklist.

Notes: Reproduced from Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(6):e1000097.¹⁰ For more information, visit: www.prisma-statement.org.

Figure S2 Risk of bias and applicability concerns graph: review authors’ judgments about each domain presented as percentages across included studies.

Figure S3 Risk of bias and applicability concerns summary: review authors’ judgments about each domain for each included study.

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