TABLE 2.

Clinical trials evaluating safety and efficacy of oral vs. intravenous (i.v.) etoposide regimen in SCLC

Trial(ref.)	Sample size	Treatment regimen	Results (oral etoposide regimen vs. i.v. etoposide regimen)
			ORR (%)	mPFS (months)	mOS (months)	toxicity
Randomized phase II24	83 patients	i.v. etoposide regimen (41 patients): cisplatin 100 mg/m2 i.v. day 1, etoposide 120 mg/m2 i.v. day 1–3	50 vs. 59	5.9 vs. 6.6	8.6 for either treatment arm	hematologic toxicity comparable in both treatment arms, infectious episodes, moderate to severe anemia and weight loss more predominant with the i.v regimen
		oral etoposide regimen (42 patients): cisplatin 100 mg/m2 i.v. day 1, etoposide 120 mg/m2 i.v. day 1 and 240 mg/m2 orally day 2 and 3
		Every 4 weeks, maximum of 6 cycles.
Randomized phase II89,90	47 patients	i.v. etoposide regimen (22 patients): etoposide 80 mg/m2 i.v. 5 consecutive days	similar for either treatment arm (PR: 28 vs. 36.4)	/	/	leukopenia observed in 32% patients of the oral administration and in 59% patients of the i.v. administration
		oral etoposide regimen (25 patients): etoposide 130 mg/m2 orally 5 consecutive days
Randomized trial91	21 patients	i.v. etoposide regimen (14 patients): cisplatin 80 mg/m2 i.v. day 1, etoposide 100 mg/m2 i.v. day 2, 3 and 4	86 vs. 64	/	no significant difference	hematologic toxicity less severe for oral regimen than for i.v. regimen
		oral etoposide regimen (7 patients): cisplatin 80 mg/m2 i.v. day 1, etoposide 50 mg orally day 3–23
		Both regimens were repeated every 4 weeks.
Randomized phase III92	306	i.v. etoposide regimen: cisplatin 25 mg/m2 i.v. 3 days, etoposide 130 mg/m2 i.v. 3 days Regimen was repeated every 21 days for 8 cycles.	14 vs. 15 (PR: 47 vs. 42)	7 months for either treatment arm	9.9 vs. 9.5	lethal toxicity due to neutropenia and infection: in 10% of patients on oral etoposide regimen and in 4% on i.v. etoposide regimen (difference not statistically significant)
		oral etoposide regimen: cisplatin 33 mg/m2 i.v. 3 days, etoposide 50 mg/m2 orally 21 days Regimen was repeated every 28 days for 6 cycles.
Randomized trial93	339 patients	i.v. etoposide regimen (168 patients): standard intravenous regimen of etoposide and vincristine, or cyclophosphamide, doxorubicin, and vincristine, 4 cycles	45 vs. 51	/	4.3 vs. 6.1	grade 2 or worse haematological toxicity: in 29% of patients on oral etoposide regimen and in 21% on i.v. etoposide regimen
		oral etoposide regimen (171 patients): etoposide 50 mg orally twice daily for 10 days, 4 cycles
Randomized trial94	155 patients	i.v. etoposide regimen (80 patients): intravenous regimen consisting of alternating cycles of etoposide and cisplatin and cyclophosphamide, doxorubicin, and vincristine	32.9 vs. 46.3	3.6 vs. 5.6	4.8 vs. 5.9	toxicity similar in the two treatment arms
		oral etoposide regimen (75 patients): etoposide 100 mg orally twice daily for 5 days
		Both regimens were repeated every 21 days for 6 cycles.

ORR = overall response rate; mPFS = median progression free survival; mOS = median overall survival; PR = partial respons