Aarts Frits, Hendriks Thijs, Boerman Otto C, Oyen Wim J G, Bleichrodt Robert P
Department of Surgery, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Cancer Biother Radiopharm. 2008 Jun;23(3):301-9. doi: 10.1089/cbr.2007.0455.
Cytoreductive surgery (CS) and heated intraperitoneal chemotherapy (HIPEC) are standard treatment for peritoneal carcinomatosis (PC) of colorectal cancer. Previously, we demonstrated that preclinical radioimmunotherapy (RIT) adjuvant to surgery in PC is a good alternative for HIPEC. Now we aimed to improve the effectiveness of RIT by combining it with whole-body hyperthermia (WBH) or fibrinolytic therapy.
Rats were inoculated intraperitoneally with colon carcinoma cells. Animals underwent CS, CS + WBH (40 degrees C, 3 hours), CS + RIT (74 MBq 177Lu-labeled MG1), or CS + WBH + RIT. In the second experiment, rats underwent CS, CS + RIT, CS + recombinant tissue plasminogen activator (rtPA, twice daily, 3 days), or CS + RIT + rtPA.
Median survival after CS and CS + WBH was 34 and 37 days. Median survival after CS + RIT or CS + RIT + WBH was 63 and 86 days (p < 0.0003, p < 0.0006 compared to CS + WBH). Median survival after CS and CS + rtPA was 50 and 42 days (p = 0.1). Median survival was 106 days after CS + RIT and 103 days after CS + RIT + rtPA (p < 0.0001 compared to CS + rtPA). No difference was found between CS + RIT and CS + RIT + rtPA (p = 0.83).
The application of WBH or rtPA in combination with adjuvant RIT after CS for the treatment of PC of colonic was feasible but did not significantly potentiate the efficacy of RIT.
细胞减灭术(CS)及热灌注化疗(HIPEC)是结直肠癌腹膜转移癌(PC)的标准治疗方法。此前,我们证明了PC手术辅助的临床前放射免疫疗法(RIT)是HIPEC的良好替代方案。现在我们旨在通过将其与全身热疗(WBH)或纤维蛋白溶解疗法相结合来提高RIT的有效性。
给大鼠腹腔内接种结肠癌细胞。动物接受CS、CS + WBH(40℃,3小时)、CS + RIT(74MBq 177Lu标记的MG1)或CS + WBH + RIT。在第二个实验中,大鼠接受CS、CS + RIT、CS +重组组织型纤溶酶原激活剂(rtPA,每日两次,共3天)或CS + RIT + rtPA。
CS及CS + WBH后的中位生存期分别为34天和37天。CS + RIT或CS + RIT + WBH后的中位生存期分别为63天和86天(与CS + WBH相比,p < 0.0003,p < 0.0006)。CS及CS + rtPA后的中位生存期分别为50天和42天(p = 0.1)。CS + RIT后的中位生存期为106天,CS + RIT + rtPA后的中位生存期为103天(与CS + rtPA相比,p < 0.0001)。CS + RIT与CS + RIT + rtPA之间未发现差异(p = 0.83)。
CS后将WBH或rtPA与辅助性RIT联合应用于结肠PC的治疗是可行的,但并未显著增强RIT的疗效。