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. Author manuscript; available in PMC: 2019 Jan 15.
Published in final edited form as: Cancer Res. 2017 Nov 29;78(2):558–571. doi: 10.1158/0008-5472.CAN-17-1700

Fig. 6. PDP and multi-cycle nal-IRI achieve durable and significant survival enhancement and reduce endpoint disease burden in two orthotopic PDAC models.

Fig. 6

(A) Swiss nude mice were orthotopically inoculated with MIA PaCa-2 or AsPC-1 cells, divided into four groups, and subjected to (1) no-treatment; (2) PDP (day 9 post-implantation; nal-BPD 0.25 mg/kg; 690 nm light at 100 mW/cm2 to achieve 75 J/cm2); (3) multiple cycles of nal-IRI (nal-IRI; four doses at 20 mg/kg each, on days 9, 12, 17 and 21 post-implantation); and (4) PDP+nal-IRI. Moribundity was used as the endpoint for the survival study with proper justification and special approval by the MGH IACUC. Animals were monitored for up to 450 days (15 months). (B, C) Kaplan-Meier plot of overall animal survival (B) and progression-free survival (C) in MIA PACa-2 model. (n = 9–13 animals per group). (D) Kaplan-Meier plot of animal overall survival in the AsPC-1 model. (n = 4–7 animals per group). (E) Median survival time, hazard ratio forest plot, and differences in survival were evaluated by the log-rank test. A global test demonstrated a difference exists among the groups. Specifically, pairwise comparisons were performed to evaluate the advantage of treatment over no-treatment. Animals treated with PDP+nal-IRI were found to be significantly less likely to die by the next time point (hazard ratio < 1). No advantage to monotherapies (compared to no-treatment) were observed. Primary tumor weight, metastatic burden, and ascites volume were evaluated at animal death or day 450. (F) The combination of PDP+nal-IRI significantly reduced the endpoint primary tumor weight by half compared to the monotherapies and the no-treatment group. (n = 3–5 animals per group, *P<0.05, Unpaired t test). (G) The ascites formation in moribund animals were significantly reduced after ‘nal-IRI’ and ‘PDP+nal-IRI’ treatments, compared to the ‘no-treatment’ arm. (n = 3–6 animals per group; (*P<0.05, **P<0.01, Unpaired t test). Asterisks denote significance compared with no-treatment group or amongst the indicated groups at each time point. Results are mean ± standard error of the mean (SEM).