Abstract:
Objective This work aimed to study the efficacy and safety of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) combined with targeting anti-tumor drug Ac-Phe-Lys-PABC-DOX (PDOX) for treating the gastric cancer rabbit models with peritoneal carcinomatosis (PC).
Methods VX2 tumor cells were injected into the gastric sub-mucosa of 40 adult male New Zealand rabbits using a laparotomic inoculation technique and laparoscopy in order to construct the gastric cancer rabbit model with PC. The rabbits were randomly divided into 4 groups: the Control group (n=10) without any treatment, the HIPEC group (n=10) receiving CRS plus HIPEC (docetaxel 10.0mg and carboplatin 50.0 mg in 250 mL normal saline, at 42.5 ± 0.5℃ for 30 min), the PDOX group (n= 10) receiving systemic chemotherapy with PDOX 50.0 mg/kg (10.0 mg/kg every 4 d for 5 cycles) after CRS+HIPEC, and the DOX group (n=10) receiving systemic chemotherapy with DOX 5.0 mg/kg (1.0 mg/kg every 4 d for 5 cycles) after CRS+HIPEC. The CRS+HIPEC regimen was performed for a total of 8 d, while the systemic chemotherapy was initiated 16 d after model construction. The primary endpoint was overall survival (OS), and the secondary endpoint was safety profile.
Results Rabbit PC model was successfully established in all animals (100%, 40/40). The median (95% confidence interval CI) survivals were 23.0 d (19.9 d to 26.1 d) in the Control group, 41.0 d (36.9 d to 45.1 d) in the HIPEC group, 58.0 d (39.6 d to 54.4 d) in the PDOX group, and 65.0 d (44.1 d to 71.9 d) in the DOX group. Compared with the Control group, the OS was extended by at least 70% in the HIPEC group (P < 0.001). Compared with the HIPEC group, the OS was extended by at least 40% in the PDOX and DOX groups (P=0.029, PDOX vs. HIPEC; P=0.021, DOX vs. HIPEC). There were no differences in the blood cell count, liver and kidney functions, creatine kinase (CK), CK-MB, and lactate dehydrogenase (LDH) between the 2 groups at the same time point. The values of white blood cell and platelet were significantly lower in the DOX than in the HIPEC group, after the systemic chemotherapy (P < 0.05).
Conclusion The regimen of CRS plus HIPEC could bring survival benefits to the gastric cancer rabbit model with PC. Furthermore, the addition of molecular targeted therapy with PDOX could bring about better survival benefits with more satisfactory drug safety.