Non-Cross Resistant Sequential Single Agent Chemotherapy in First-Line Advanced Non-Small Cell Lung Cancer Patients: Results of a Phase II Study

Table 1

Overview of the sequential studies reported in the literature.

Study	Phase	𝑁=	Regimen	RR (%)	PD(%)	MS (m)	1year OS (%)	PFS (m)	Major grade 3-4 toxicity(%)
Doublet→Doublet
Gebbia (9)	III	400	G + IFO (2)→CDDP + VNR (2); versus	19	59	NR	NR	3.1^a	Neutropenia 57/67/26/21; Thrombo 32/35/17^b/41; Vomiting 13/15/21/23; Asthenia 29/35/35^c/50
			CDDP + VNR (2)→G + IFO (2); versus	32	33	NR	NR	5
			CDDP + VNR (up to 6 cycles); versus	44^a	25	9	24	4.1
			CDDP + G (up to 6 cycles)	34	37	8.2	20	4
Doublet → SA
Edelman (10)	III	204	CBDCA + G (3)→PTX(3); versus	21	29	9	34	4	Neutropenia 47^a/70; Anemia 19/14
			CDDP + VNR (3)→DOC(3)	28	22	9	36	4	Thrombocytopenia 37/2^a; Fatigue 7^a/18; Emesis 5^a/24; Toxic deaths 3/3
Clark (11)	II	18	CDDP (2) + VNR(2)→ DOC (4)	31	44	9.5	44	NR	Leukopenia 45^d; Emesis 26^d; Toxic deaths 3
Grossi (12)	II	51	CDDP + PTX (2)→VNR( 2)→G (2)	43	25	14	53	6.8	Neutropenia 41; Toxic deaths 1
Kubota (13)	III	401	CBDCA + PTX (up to 6); versus	36^a	10	13.8	55.5	6	Neutropenia 54/30^a; Neuropathia 21/2^a; Toxic deaths 0/2
			VNR + G (3) → DOC (3)	23	16	13.1	55.6	5.9
SA→doublet or triplet
Feliu (14)	II	52	PTX (6)→ CDDP + GEM + VNR (up to 6)	56	31	NR	56	9	Neutropenia 20; Neuropathy 12; Emesis 10
Rixe (15)	II	32	DOC (4)→ CDDP + VDS (4)	17	27	11	47	4.4	Neutropenia (gr 4) 71; Febrile neutropenia 14; Neuropathy 24
SA→SA
Present study	II	21	G →PTX	20%	50	8	33	3	Neutropenia 4; Neuropathy 9
Manegold(16)	II-III	338	G +DOC (6); versus	33^a	NR	7.3	27	6.3^a	Neutropenia 36/27; Infection 17/13
			G (3) →DOC (3)	22	NR	7.4	25	4.9	Dyspnoe 21/20; Asthenia 12/11
Martoni (17)	II	52	G(3) →VNR (until PD)	23	23	10	42	6	Neutropenia 22^e; Constipation 3^e
Poon (18)	II	23	G (3) → CDDP (4)	21	52	14.6	63	3.3	Neutropenia 13; Anemia 13
Hirsch (19)	II	42	VNR (2) →G	38	36	8	29	3.5	No grade 3-4; tox.
Tibaldi (20)	II	56	G (3)→ DOC (3)	16	43	8	34	4.8	Neutropenia 5.4; Thrombopenia 3.6; Mucositis 3.6; Diarrhea 3.6; Asthenia 9

(a) statistically significant,
(b) difference in thrombocytopenia incidence between CT arms was statistically significant (𝑃 = .0001).
(c) asthenia more frequent in the GC arm than VC arm (50% versus 35%, 𝑃=.015).
(d) toxicity evaluated per cycle,
(e) worst toxicity per step,
G: gemcitabine, IFO: ifosfamide; CDDP: cisplatin; VNR: vinorelbine; CBDCA: carboplatin; PTX: paclitaxel; DOC: docetaxel; RR: response rate; MS: median survival; MPFS: median progression-free survival; NR: not reported; OS: overall survival; PD: progressive disease; SA: single agentNR: not reported.