Table 7.

Diflomotecan (BN80915/BN-80915)

Key	Route & dose	Formulation	Cancer type and key clinical trial outcome	Refs
2003 Phase I	1/3 h iv d1 once; po d1 -5 at 0.1-0.35 mg/m2/d; 3 wk/c: 57c/24 pts	Drug dissolved in DMA for iv or po routes	22 pts w solid tumors; DLT: TCP, NP; Phase II/MTD: 0.27 mg/m2/d; SD: 6 pts; PK studies is one major focus	No 1 [274]
2004 Phase I	1/3 h iv d1 once; po d1 -5 at 0.1-0.35 mg/m2/d; 3 wk/c: 57c/24 pts	Drug dissolved in DMA for iv or po routes	22 pts w advanced refractory solid tumors; ABCG2 allele polymorphism affect diflomotecan exposure; inter-patient variation could be large	No 2 [269]
2006 Phase I	1/3 h iv d1 once at 2, 4, 5, 6 mg/m2; 3 wk/c: 75 c/24 pts	Drug dissolved in DMA for iv routes	24 pts w advanced refractory solid tumors; DLT: hematopoietic toxicity; SD: 7 pts; PD: 17 pts; MTD vs. Phase II: 5 vs. 4 mg/m2	No 3 [275]
2007 Phase I	1/3 h iv d1-5 at 0.05-0.15 mg/m2/d; 3 wk/c: 89 c/30 pts	Drug dissolved in DMA for iv routes	30 pts w advanced solid tumors; SD: 7 pts; PD: 1 pt; SD: 8 pts; MTD vs. Phase II: 0.15 vs. 0.125 mg/m2/d; large inter-patient variation of PK.	No 4 [270]
2009 Phase I	1/3 h iv d1 once at 2, 4, 7 mg/m2; 3 wk/c: 22 c/13 pts	Not clear in the publication	13 pts w advanced refractory solid tumors; DLT: NP; only 1 pt w minor response; PK & toxicity prediction is not better than po.	No 5 [271]