Tumor priming enhanced antitumor efficacy of doxorubicin HCl liposomes without enhancing toxicity
Partial response means >50% tumor size reduction. Progressive disease means >50% tumor size increase. Stable disease means <50% tumor size reduction or <50% tumor size increase. Mean ± S.D. NA, not applicable.
Vehicle, No Drug (n = 6) | Paclitaxel (n = 6) | Doxorubicin HCl Liposomes (n = 6) | Doxorubicin HCl Liposomes → Paclitaxel (n = 9) | Paclitaxel → Doxorubicin HCl Liposomes (n = 6) | |
|---|---|---|---|---|---|
| Efficacy | |||||
| Best response | |||||
| Partial response | |||||
| No. of mice (fraction) | 0 | 2 (33%) | 6 (100%) | 5 (56%) | 6 (100%) |
| Onset (median, days) | NA | 10 | 14 | 14 | 9 |
| Duration (median, days) | NA | 12 | 10 | 19 | 29 |
| Stable disease | |||||
| No. of mice (fraction) | 0 | 4 (67%) | 0 | 0 | 0 |
| Duration (median, days) | NA | 17 | NA | NA | NA |
| Progressive disease | |||||
| No. of mice (fraction) | 6 (100%) | 0 | 0 | 0 | 0 |
| Maximal tumor size reduction (%) | None | 15 ± 48 | 74 ± 15 | 89 ± 6 | 95 ± 1* |
| Median survival time (days) | 22.5 | 42 | 63 | 65 | 78* |
| Gross toxicity | |||||
| Maximal body weight loss (%) | 4 ± 1 | 4 ± 3 | 27 ± 5 | 28 ± 5 | 24 ± 6† |
| Lethality, no. of mice (fraction) | 0 | 0 | 0 | 4 (44%) | 0 |
↵* p < 0.05 compared with all other groups; repeated measures ANOVA for tumor growth curves, Wilcoxon signed rank test for animal survival among treatment groups.
↵† p < 0.05 compared with vehicle, no drug, paclitaxel, and doxorubicin HCl liposomes → paclitaxel groups. No significant differences compared with doxorubicin HCl liposome group, repeated measures ANOVA.