Table 1.
Result summary of PA-018 therapeutic responses and toxicities
| Group | N | Treatment regimen | Median | Statistical significance | Mean BW | Deaths | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Agent | mg/kg | Route | Schedule | TTE | TGD (T-C) | Chi square | P value | Summary | Nadir | TR | NTR | ||
| 1 | 10 | placebo | – | – | – | 32.7 | – | – | – | – | −0.1 % day 14 | 0 | 0 |
| 2 | 10 | 5-FU | 100 | ip | qwk × 3 | 37.3 | 4.6 | 0.3966 | 0.5288 | ns | −5.9 % day 21 | 1 | 0 |
| 3 | 10 | irinotecan | 100 | ip | qwk × 3 | 40.8 | 8.1 | 0.5419 | 0.4616 | ns | −7.9 % day 21 | 0 | 0 |
| 4 | 10 | oxaliplatin | 10 | ip | qwk × 3 | 74* | 41.3* | 14.82 | 0.0001 | *** | −9.8 % day 21 | 0 | 0 |
| 5 | 10 | gemcitabine | 120 | ip | q3d × 4 | 37.8 | 5.1 | 1.265 | 0.2607 | ns | −5.2 % Day 39 | 1 | 0 |
| 6 | 9 | bevacizumab | 5 | ip | biwk × 5 | 68.8 | 36.1 | 4.165 | 0.0413 | a | −4.3 % day 21 | 0 | 1 |
| 7 | 9 | erlotinib | 80 | po | qd × 15 | 54.4 | 21.7 | 1.277 | 0.2585 | ne | −15.3 % day 14 | 2 | 1 |
| 8 | 10 | doxorubicin | 3 | iv | qwk × 3 | 65.8 | 33.1 | 2.525 | 0.112 | ns | −5.1 % day 42 | 0 | 0 |
| 9 | 9 | imatinib | 100 | po | qd × 28 | 33.3 | 0.6 | 0.09389 | 0.7593 | ns | −0.8 % day 21 | 0 | 1 |
The therapies used included DNA synthesis inhibitors (5-FU, gemcitabine), a DNA alkylating agent (oxaliplatin), a DNA intercalating agent (liposomal doxorubicin), a topoisomerase inhibitor (irinotecan), an EGFR inhibitor (erlotinib), a c-kit inhibitor (imatinib) and an angiogenesis inhibitor (bevacizumab). Therapies were delivered as indicated and tumor growth was continually observed after treatment regimen ceased in order to determine time-to-endpoint (TTE) and difference between median TTE of treated groups vs. placebo (T-C). Statistical significance was evaluated by logrank test, df = 1 with significance indicated by * and non-significance (ns) or not evaluable (ne). Body weight (BW) nadir was shown as percent change and deaths were divided into treatment-related deaths (TR) and non-treatment related deaths (NTR). The final sample size (n) was calculated by removing NTR deaths
n number of animals in a group not dead from accidental or unknown causes, or euthanized for sampling, TTE time to endpoint, T-C difference between median TTE (days) of treated group versus control group, TR treatment-related death, NTR non-treatment-related death, Mean BW Nadir lowest group mean body weight, as % change from day 1, ne not evaluable, ns not significant
Statistical significance (Logrank test, df = 1): * P < 0.05, ** P < 0.01, *** P < 0.001, compared to Group 1
aTime of sacrifice (74 days) was artificially used at TTE for oxaliplatin group