Clinical benefit of COX-2 inhibitors in the adjuvant chemotherapy of advanced non-small cell lung cancer: A systematic review and meta-analysis

Table 1 Characteristics of each individual study

Trials or Ref.	Year	Phase	Study period	Country	Sample (I/C)	Age (I/C)	Male (female) (I/C)	Histology (I/C) (AC, SCC, Other)	Extent of disease, Stage	ECOG PS or Karnofsky score	Treatment Line	Interventions	Control	Follow-up in mo
Lilenbaum et al[22]	2006	II	Feb 2002 to Sept 2003	United States	133 (67/66)	62.7 (37-84)/63.5 (41-78)	40 (27)/40 (26)	NA, NA, NA	ШB, IV	ECOG 0-1	Second	Celecoxib 400 mg po bid + DTX 35 mg/m2 or GEM 1000 mg/m2 + CPT-11 60-100 mg/m2 ivgtt day 1 and day 8, q3w	DTX 35 mg/m2 or GEM 1000 mg/m2 + CPT-11 60-100 mg/m2 ivgtt day 1 and day 8, q3w	NA
GECO[23]	2007	Ш	Jan 2003 to May 2005	Italy	400 (149/251)	61.5 (29-71)/59.0 (37-70)	120 (29)/202 (49)	68/134, 47/53, 34/64	ШB, IV	ECOG 0-1	First	Rofecoxib 50 mg po qd + GEM 1200 mg/m2 in 30-min or PCI GEM 1200 mg/m2 over 120-min iv infusions days 1 and 8 + DDP 80 mg/m2 ivgtt qd day 1, q3w	GEM 1200 mg/m2 in 30-min or PCI GEM 1200 mg/m2 over 120-min iv infusions days 1 and 8 + DDP 80 mg/m2 ivgtt qd day 1, q3w	22
Zhou et al[29]	2007	II	June 2004 to June 2005	China	65 (32/33)	57.0 (45-77)/55.5 (40-76)	24 (8)/24 (9)	17/19, 9/8, 5/3	ШB, IV	ECOG 0-2	First	Celecoxib 400 mg po bid days 1-12 + NVB 25 mg/m2 iv qd day 1 and 8 + DDP 75 mg/m2 ivgtt qd days 1 and 2, q3w	NVB 25 mg/m2 iv qd days 1 and 8 + DDP 75 mg/m2 ivgtt qd days 1 and 2, q3w	NA
Xiong et al[28]	2008	II	Jan 2003 to Jan 2006	China	60 (30/30)	56.4/58.3	16 (14)/17 (13)	16/17, 10/10, 4/3	ШB, IV	ECOG 0-2	First	Celecoxib 400 mg po bid + NVB 25 mg/m2 iv qd days 1 and 8 + DDP 70 mg/m2 ivgtt qd days 1-3, q3w	NVB 25 mg/m2 iv qd days 1 and 8 + DDP 70 mg/m2 ivgtt qd days 1-3, q3w	NA
CYCLUS[24]	2011	Ш	May 2003 to May 2006	Sweden	316 (158/158)	66 (38-85)/65 (37-85)	73 (85)/87 (71)	77/94, 38/27, 43/36	ШB, IV	ECOG 0-2	First	Celecoxib 400 mg po bid + GEM or NVB + CBP or DDP, ivgtt q3w1	Placebo + GEM or NVB + CBP or DDP, ivgtt q3w	36
NVALT-4[25]	2011	Ш	July 2003 to Dec 2007	Netherlands	561 (281/280)	62 (40-84)/61 (33-84)	184 (97)/171 (109)	138/132, 44/57, 99/91	ШB, IV	ECOG 0-2	First	Celecoxib 400 mg po bid + DTX 75 mg/m2 ivgtt qd day 1 + CBP ivgtt qd day 1, q3w2	Placebo + DTX 75 mg/m2 ivgtt qd day 1 + CBP ivgtt qd day 1, q3w	NA
Liu et al[30]	2012	NA	Jan 2006 to May 2011	China	46 (24/22)	62 (49-75)/64 (52-76)	14 (10)/15 (7)	15/14, 9/8, 0/0	ШB, IV	Karnofsky ≥ 70	First	Celecoxib 400 mg po bid days 1-5 + DTX 75 mg/m2 ivgtt qd day 1 + DDP 100 mg/m2 ivgtt qd day 1, q3w	DTX 75 mg/m2 ivgtt qd day 1 + DDP 100 mg/m2 ivgtt qd day 1, q3w	NA
Sörenson et al[32]	2013	Ш	May 2006 to May 2009	Sweden	107 (52/55)	65 (37-84)	50/57	65, 16, 26	ШB, IV	NA	First	Celecoxib at a dose of 400 mg bid + carboplatin plus gemcitabine/vinorelbine	Carboplatin + gemcitabine/ vinorelbine	5
Gitlitz et al[33]	2014	II	NA	United States	120 (78/42)	63 (35-81)/65 (36-84)	78 (42)/42 (25)	45/24, 21/11, 12/7	ШB, IV	ECOG 0-2	Second	Apricoxib (400 mg/d) + erlotinib (150 mg/d) on 21-d cycles	Placebo + erlotinib (150 mg/d) on 21-d cycles	NA
0822-GCC[26]	2015	II	NA	United States	72 (36/36)	62/66	20 (16)/20 (16)	24/25, 8/6, 4/5	ШB, IV	ECOG 0-2	Second	Apricoxib 400 mg po qd + DTX 75 mg/m2 or PET 500 mg/m2, q3w	Placebo 400 mg po qd DTX 75 mg/m2 or PET 500 mg/m2, q3w	NA
Teng et al[31]	2015	II	Aug 2009 to May 2012	China	81 (41/40)	57.7 (28-72)/57.3 (33-76)	30 (11)/26 (14)	28/26, 13/14, 0/0	ШB, IV	ECOG 0-1	First	Celecoxib 200 mg po bid + NVB 25 mg/m2 ivgtt days 1 and 8 + DDP 70 mg/m2 ivgtt qd day 1, q4w	NVB 25 mg/m2 ivgtt days 1 and 8 + DDP 70 mg/m2 ivgtt qd day 1, q4w	NA
CALGB-30801[27]	2017	Ш	Nov 2013 to Jan 2016	United States	312 (154/158)	64 (38-83)/64 (36-89)	82 (72)/87 (71)	NA, 44/43, NA	ШB, IV	ECOG 0-2	First	Celecoxib 400 mg po bid + CBP + PET 500 mg/m2 day 1, q3w for nonsquamous or Celecoxib 400 mg po bid + CBP day 1 + GEM 1000 mg/m2 day 1 and day 8, q3w for squamous	Placebo + CBP + PET 500 mg/m2 day 1, q3w for nonsquamous or placebo + CBP day 1 + GEM 1000 mg/m2 day 1 and day 8, q3w for squamous	31

¹The dose of chemotherapeutic agents was not mentioned in the trial. ²The dose of carboplatin was not mentioned in the trial. AC: Adenocarcinoma; I/C: Interventions/Control; Bid: Twice daily; CBP: Carboplatin; CR: Complete response; d: Day; DDP: Cisplatin; DTX: Docetaxel; iv: Intravenously; ECOG PS: Eastern Cooperative Oncology Group performance status; GEM: Gemcitabine; ivgtt: Intravenous drip; PCI: Prolonged constant infusion; NA: Not applicable; NVB: Vinorelbine; PET: Pemetrexed; OS: Overall survival; PFS: Progression free survival; Po: Orally; PR: Partial response; SCC: Squamous cell carcinoma; q: Every; w: Weeks.