Cytoreductive surgery and radioimmunotherapy to treat peritoneal carcinomatosis of colorectal cancer : investigations towards improvement of outcome and morbidity

Abstract

The clinical treatment of first choice for peritoneal carcinomatosis of colorectal cancer is HIPEC. In order to improve outcome and morbidity, new treatment strategies have been developed, one of which is radioimmunotherapy. The results of clinical trials investigating regionally administered radioimmunotherapy are described in Chapter 2. In Chapter 3, it was investigated whether survival after intraperitoneally administered RIT can be enhanced by altering the time interval between the surgical procedure and the intraperitoneal administration of RIT. We concluded that the efficacy of adjuvant RIT after cytoreductive surgery (CS) for the treatment of experimental PC of colonic origin decreases when the administration of the radiolabeled MAbs is postponed. In Chapter 4, the concomitant administration of rtPA or wholebody hyperthermia after CS and RIT was investigated. We concluded that both applications did not significantly potentiate RIT. In Chapter 5, RIT was than compared to HIPEC, where survival after CS was significantly improved by RIT whereas adjuvant HIPEC did not and was more toxic than RIT. In Chapter 6, the effects of adjuvant RIT or HIPEC after CS on the healing of bowel anastomoses and abdominal wall was investigated. We concluded that RIT is superior to HIPEC regarding anastomotic and abdominal wall wound strength in a model of PC of CRC. In Chapter 7 we investigated whether carbohydrate modifications of the antibody could improve pharmacokinetics of the intraperitoneally administered antibody. This resulted in improved tumor-non-tumor ratios and thus might improve RIT, especially in combination with short-lived non-residualizing radionuclides. The data of a patient study where a two-step pretargeting radioimmunoscintigraphy technique was used, are presented in Chapter 8, where the optimal time interval between the administration of the antibody and the radiolabeled peptide was investigated in patients with colorectal cancer. These data show the best time interval to be four days after Ab injection.