A comparative in vivo study of hyperthermic intraperitoneal chemotherapy with cisplatin versus doxorubicin versus cisplatin plus doxorubicin for the treatment of intra-abdominally disseminated alveolar rhabdomyosarcoma in mice

Background

Treatment options for advanced intra-abdominal pediatric rhabdomyosarcoma (RMS) with peritoneal sarcomatosis (PS) include cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). However, optimal dosages and combination regimens of drugs used for HIPEC are underexplored. We aimed to evaluate the efficacy of HIPEC with cisplatin, doxorubicin, and their combination in vivo.

Methods

We established PS/RMS mouse model by intraperitoneally injecting RH30 cells into NOD/LtSz-scid IL2Rγ-null mice. Two weeks post xenotransplantation, mice underwent a single HIPEC procedure at 42°C for 60 minutes. Treatment groups received cisplatin (50, 100, and 150 mg/m²) and doxorubicin (30, 45, and 60 mg/m²), administered alone or combined. The control group underwent an intraperitoneal lavage with isotonic saline. Peritoneal cancer index (PCI) was used to quantify the extent of peritoneal tumor spread. Tissue samples were evaluated regarding proliferation (Ki-67) and apoptosis (caspase 3).

Results

Mice treated with cisplatin at 100 mg/m² (PCI of 3.875, p = .007) and 150 mg/m² (PCI of 4.556, p = .026), and doxorubicin at 30 mg/m² (PCI of 2.875, p < .001) and 45 mg/m² (PCI of 4.143, p = .021) showed reduced PCI, with the combination of cisplatin 50 mg/m² and doxorubicin 30 mg/m² showing the most prominent effect (PCI of 3.333, p < .001) compared to the control group (PCI of 8.615). Histologically, there was no difference in Ki-67 or caspase 3 expression among the groups.

Conclusions

The cisplatin- and doxorubicin-based HIPEC significantly reduces peritoneal tumor dissemination in vivo. Further investigations are needed to explore the underlying molecular responses to optimize therapeutic strategies.