Animal Model | Formulation | Dose | ILS8-a | p |
---|---|---|---|---|
mg/kg | % | |||
Fischer rats (fibrous histiocytoma)8-e | Doxil | 8 | 65 | <.0003 |
Free DOX | 8 | 35 | <.05 | |
Doxil | 5 × 3 | 89 | <.00001 | |
Free DOX | 5 × 3 | 23 | <.05 | |
CD2F1 mice (P-1798 lymphosarcoma)8-f | DaunoXome | 20 | 15 | <.05 |
Free daunorubicin | 20 | 54 | <.05 | |
B6C3F1 mice (MA16C mammary adenocarcinoma)8-f | DaunoXome | 20 | >217 | <.05 |
DaunoXome | 2 | 100 | <.05 | |
Free daunorubicin | 20 | 94 | ||
Nude mice (ovarian HEY cancer)8-g | Doxil | 9 | 40 | <.001 |
Free DOX | 9 | −50 | ||
Female BALB/c mice (C26 colon carcinoma)8-h | PEG-DSPE/HSPC/Chol (DOX) | 10 | 48.3 | |
DSPC/Chol (2:1) | 10 | 5.1 | NS | |
Free DOX | 10 | −4.2 | NS | |
BALB/c mice (J6456 lymphoma) | Doxil | 10 (i.v.) | 116 | <.0001 |
Free DOX | 10 (i.v.) | 21 | <.0001 | |
Doxil | 10 (i.p.) | 60.5 | <.0001 | |
Free DOX | 10 (i.p.) | 60.5 | <.0001 | |
Female BALB/c mice (C26 colon carcinoma)8-j | PEG-DSPE/HSPC/Chol (DOX) | 10 | −7 | |
DSPC/Chol (1:1) | 10 | 21 | ||
Free DOX | 10 | 114 | ||
BALB/c mice (M-109 carcinoma)8-k | PEG-DSPE/DSPC/Chol (DOX) | 10 | 168 | <.05 |
PEG-DSPC/DPPC/Chol | 10 | 118 | ||
DSPG/HSPC/Chol | 10 | 168 | <.1 | |
HSPC/Chol | 10 | 94 | ||
Free DOX | 10 | 97 | ||
BALB/c mice (J6456 lymphoma)8-k | PEG-DSPE/DSPC/Chol (DOX) | 15 | 144 | <.01 |
DSPG/HSPC/Chol | 15 | 197 | <.01 | |
Free DOX | 15 | 19 | ||
BALB/c mice (C26 colon carcinoma)8-l | PEG-DSPC/DSPC/Chol (epirubicin) | 6 × 3 | 1488-b | |
Free epirubicin | 6 × 3 | 20 | ||
BDF1 mice (P388 lymphoma)8-m | DSPC/Chol (55:45) (VCR) | 3 | 38 | <.05 |
SM/Chol (55:45) | 3 | 214 | <.05 | |
Free VCR | 3 | >445 | <.05 | |
B6D2F1 mice (P388 leukemia)8-n (i.p.) | PEG-DSPE/DSPC/Chol (VCR) | 2 | 199 | <.018-c |
Free VCR | 2 | 79 | <.018-c | |
BDF1 mice (L1210 tumors)8-o | DSPC/Chol (mitoxanthrone) | 20 | 189 | |
DMPC/Chol | 20 | >590 | ||
Free mitoxantrone | 108-d | 98 | ||
B6D2F1 mice (L1210 leukemia)8-p (i.v.) | PEG-DSPE/DSPC/Chol (ara-c) | 50 | 138 | |
PEG-DSPE/DSPC/Chol/SM | 50 | 197 | ||
PG/DSPC/Chol | 50 | 160 | ||
Free ara-C (24-h infusion) | 50 | 90 |
The composition, size, and drug/lipid ratio for DaunoXome and Doxil are listed in Table 1.
↵8-a ILS, mean survival: 100 ∗ treated/control − 100.
↵8-b ILS was calculated only from mean survival time of mice dying before day 120 (there were 6 of 10 long-term survivors for >120 days).
↵8-c Between-treatment groups at same dose level; otherp values are between treatment and control groups.
↵8-d The mean survival time for free mitoxantrone.
↵8-e Siegal et al. (1995).
↵8-f Forssen et al. (1992).
↵8-g Vaage et al. (1994b).
↵8-h Huang et al. (1992).
8-i Cabanes et al. (1998).
↵8-j Unezaki et al. (1995).
↵8-k Gabizon et al. (1996).
↵8-l Mayhew et al. (1992).
↵8-m Webb et al. (1995).
↵8-n Allen et al. (1995b).
↵8-o Lim et al. (1997).
↵8-p Allen et al. (1992).