A comparison between radioimmunotherapy and hyperthermic intraperitoneal chemotherapy for the treatment of peritoneal carcinomatosis of colonic origin in rats

Abstract

Background: Cytoreductive surgery (CS) followed by heated intraperitoneal chemotherapy (HIPEC) is considered the standard of care for the treatment of patients with peritoneal carcinomatosis (PC) of colorectal cancer (CRC). These surgical procedures result in a median survival of 2 years at the cost of considerable morbidity and mortality. In preclinical studies, radioimmunotherapy (RIT) improved survival after CS in a model of induced PC of colonic origin. In the present studies we aimed to compare the efficacy and toxicity of CS followed by adjuvant RIT in experimental PC to the standard of care, HIPEC.

Methods: PC was induced by intraperitoneal inoculation of CC-531 colon carcinoma cells in three groups of Wag/Rij rats. Treatment comprised CS only, CS + RIT or CS + HIPEC, immediately after surgery. RIT consisted of intraperitoneal administration of 74 MBq Lutetium-177 labeled MG1. HIPEC was performed by a closed abdomen perfusion technique using mitomycin C (16 mg/L during 60 minutes). The primary endpoint was survival.

Results: CS only or combined with RIT was well tolerated. Rats receiving CS + HIPEC were lethargic, suffered from diarrhea, and lost significantly more weight in the first postoperative week. Median survival of rats treated with CS + RIT was significantly longer than after CS alone (97 and 57 days, respectively, P < .004), whereas survival after CS + HIPEC or CS alone were not significantly different (76 and 57 days, respectively, P = .17).

Conclusion: Survival after CS was significantly improved by RIT with Lutetium-177-MG1 in rats with PC of colorectal origin. Adjuvant HIPEC did not improve survival and was more toxic than adjuvant RIT.

FIG. 1.

HIPEC Perfusion System; MMC Mitomycin C Kyowa 16 mg/L perfusate. Adapted from Ref. 19. Reproduced with permission.

FIG. 2.

Intraperitoneal distribution of methylene blue stained perfusate.

FIG. 3.

The relative body weight of Wag/Rij rats after exploratory laparotomy (control) and heated intraperitoneal chemotherapy (HIPEC) given immediately postoperatively in different doses. Data represent means ± standard error of the mean (SEM).

FIG. 4.

The recorded intra-abdominal and rectal temperature during the HIPEC procedure. Data represent means ± standard error of the mean (SEM).

FIG. 5.

The relative body weight of Wag/Rij rats with small peritoneal CC-531 tumors in the first 14 days after cytoreductive surgery (CS) only, CS + radioimmunotherapy given immediately postoperatively (RIT) or heated intraperitoneal chemotherapy (HIPEC) given immediately postoperatively. Data represent means ± standard error of the mean (SEM).

FIG. 6.

Kaplan–Meier survival curves for Wag/Rij rats with small peritoneal CC-531 tumors after cytoreductive surgery (CS), CS + RIT (RIT) or CS + HIPEC (HIPEC).