Radioimmunotherapy of Colorectal Cancer Liver Metastases: Combination with Radiotherapy

Abstract

The expected therapeutic gain of a combined radioimmunotherapy (RIT) with conventional radiotherapy (RT) would be a synergy of tumor irradiation, provided that toxic, dose‐limiting side effects concern different organs. We have shown in a model of subcutaneous human colon cancer transplants in nude mice that RIT with 131I‐labeled anti‐CEA antibody fragments combined with fractionated RT give an additive therapeutic effect without increase of side effects. A second study of different timing schedules of RIT and RT has shown that close association of both therapies without delay is more efficient than a therapy with a treatment‐free interval of two weeks. In a new model of human colon cancer liver metastases in nude mice, early treatment with RIT and with RT has been curative, whereas therapies initiated later were less efficient, suggesting that the combined therapy is likely to be more efficient in an adjuvant situation after surgery. At the clinical level, six patients with limited liver metastatic disease from colorectal cancer were treated with RIT using 200 mCi 131I‐labeled anti‐CEA MAb F(ab′)2 fragments combined with fractionated external beam RT of 20 Gy to the entire liver. As expected, spontaneously reversible bone marrow toxicity grade 3 to 4 and reversible liver toxicity grade 1 to 3 have been observed. By computerized tomography, three patients showed stable disease and one patient partial remission, whereas two patients had progressive disease. In conclusion, animal experiments have shown a clear advantage of combined RT and RIT, and the clinical study shows the feasibility of such a therapy in patients with colorectal cancer liver metastases.

Compartmental intrathecal radioimmunotherapy: results for treatment for metastatic CNS neuroblastoma

“…We also note the encouraging preclinical data demonstrating the enhanced therapeutic effect of combination external beam radiation therapy and cRIT, compared to that observed with either therapy alone. [25, 26] This combination of reduced-dose craniospinal irradiation aimed at controlling bulk parenchymal and nodular LM disease and cRIT targeting micrometastic NB, may well be contributing to the prolonged survival seen in our patient cohort.…”

Improved outcome of 131 I-mIBG treatment through combination with external beam radiotherapy in the SK-N-SH mouse model of neuroblastoma

“…In addition it may not be possible to proceed with EBRT immediately after administration of MRT since patients often require stem cell rescue following 131 I-mIBG. However, it is well documented that MRT given concurrently with EBRT is more effective than when given after a prolonged interval [25] , [26] , [27] . Therefore if it were possible to separate the two radiation modalities without affecting their combined efficacy it would avoid added complexities in the clinical management of paediatric patients.…”

Cancer Radioimmunotherapy

“…Enhancing uptake by modifying the tumor’s vascular properties through hyperthermia, radiation, or biologically active compounds has been widely investigated [144–150], but these manipulations usually have only a modest effect on antibody uptake. Locoregional administration, such as intraperitoneal and intracranial, is another example of modifying the route of administration in order to give an antibody a ‘first-pass’ opportunity to bind to the tumor, enhancing uptake [151].…”