Radioimmunotherapy of small-volume disease of metastatic colorectal cancer.
BACKGROUND
Whereas radioimmunotherapy (RIT) has shown disappointing results in bulky, solid tumors, preclinical results in small-volume disease and in an adjuvant setting are promising. In a previous Phase I study, the authors had encouraging results with the iodine-131 ((131)I)-labeled humanized anti-carcinoembryonic antigen (anti-CEA) antibody (MAb) hMN-14 in small-volume disease of colorectal cancer. The aim of this study was to evaluate, in a subsequent Phase II trial, the therapeutic efficacy of this (131)I-labeled humanized anti-CEA antibody in colorectal cancer patients with small-volume disease or in an adjuvant setting.


METHODS
Thirty colorectal cancer patients, with small-volume metastatic disease (n = 21; all lesions less-than-or-equal 3.0 cm, and chemorefractory to 5-fluorouracil and folinic acid) or in an adjuvant setting (n = 9), 4-6 weeks after surgical resection of liver metastases with curative intention, were studied. The patients were given a single injection of (131)I-hMN-14 immunoglobulin G at a 60 mCi/m(2) dose level, which was shown to be the maximum tolerated dose in the previous Phase I study. Follow-up was obtained at 3-month intervals for as long as 36 months.


RESULTS
At a mean blood-based red marrow dose of 1.8 +/- 0.8 Gy, myelotoxicity was the only toxicity observed, but only 1 of 28 assessable patients developed transient Grade 4 thrombocytopenia. Of the 21 patients with radiologically documented lesions, 19 were assessable. Three experienced partial remission and eight showed minor responses up to 15 months in duration (corresponding to an objective response rate of 16% and an overall response rate of 58%; the mean duration of response was 9 months). At the time this article was written, seven of nine patients in the adjuvant setting had remained free of disease for up to 36 months (one patient relapsed after 6 months and another after 30 months), whereas the relapse rate in a historical control group receiving chemotherapy was 67% over the same time period. Five patients with radiologically documented lesions, having experienced at least disease stabilization as a consequence of RIT, were retreated at the same 60-mCi/m(2) dose level at 8-16 months after the first therapy. No evidence of increased toxicity was observed (no hematologic toxicity was higher than Grade 3). Two of four assessable retreated patients experienced partial remissions; one of these four again experienced disease stabilization as a consequence of the second radioantibody therapy injection.


CONCLUSIONS
These data suggest that RIT is a safe and effective form of therapy for small-volume colorectal cancer and has potential as treatment for colorectal cancer in an adjuvant setting. Toxicity is restricted to mild and transient leuko- and thrombocytopenia. Retreatment seems to be a feasible option. A prospective randomized comparison with standard chemotherapy is indicated.
Behr
Thomas M
TM
Department of Nuclear Medicine, Georg-August-University, Göttingen, Germany. behrt@mailer.uni-marburg.de
Liersch
Torsten
T
Greiner-Bechert
Lutz
L
Griesinger
Frank
F
Béhé
Martin
M
Markus
Peter M
PM
Gratz
Stefan
S
Angerstein
Christa
C
Brittinger
Gerhard
G
Becker
Heinz
H
Goldenberg
David M
DM
Becker
Wolfgang
W
D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007457:Iodine Radioisotopes / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D009362:Neoplasm Metastasis; D016499:Radioimmunotherapy; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D018796:Immunoconjugates; D007457:Iodine Radioisotopes