Continual reassessment method for dose escalation clinical trials in oncology: a comparison of prior skeleton approaches using AZD3514 data

Table 3 Comparison of dose escalation methods

			Number of patients (Order of receiving dose – DLTs are bold)						Number of patients
Method	Prior skeleton approach	MTD identified	250 Mg QD	500 Mg QD	1000 Mg QD	1000 Mg BID	2000 Mg BID	Total	Suboptimal (<1000 mg QD)	Intolerable (>1000 mg QD)
3 + 3	-	1000 Mg QD	3 (1, 2, 3)	3 (4, 5, 6)	6 (7, 8, 9, 10, 11, 12)	6 (13, 14, 15, 16, 17, 18)	0	18	6	6
Extended CRM −2^a	Conservative	1000 Mg QD	2 (1, 2)	2 (3, 4)	6 (5, 6, 7, 8, 9, 10)	2 (11, 12)	0	12	4	2
	Aggressive	1000 Mg QD	2 (1, 2)	2 (3, 4)	6 (5, 6, 7, 10, 13, 15)	5 (8, 9, 11, 12, 14)	0	15	4	5
	Step-up	1000 Mg QD	2 (1, 2)	2 (3, 4)	6 (5, 6, 7, 8, 9, 14)	5 (10, 11, 12, 13, 15)	0	15	4	5
	Dose-linear	1000 Mg QD	2 (1, 2)	2 (3, 4)	6 (5, 6, 7, 8, 11, 15)	5 (9, 10, 12, 13, 14)	0	15	4	5
	Sigmoidal	1000 Mg QD	2 (1, 2)	2 (3, 4)	6 (5, 6, 7, 8, 9, 10)	0	0	10	4	0
	O’Quigley	1000 Mg QD	2 (1, 2)	2 (3, 4)	6 (5, 6, 7, 8, 9, 10)	5 (11, 12, 13, 14, 15)	0	15	4	5
Extended CRM −3^b	Conservative	1000 Mg QD	3 (1, 2, 3)	3 (4, 5, 6)	6 (7, 8, 9, 10, 11, 14)	5 (12, 13, 15, 16, 17	0	17	6	5

^aTwo patients in each cohort prior to CRM. ^bThree patients in each cohort prior to CRM

ISSN: 1471-2407