Timing effect of combined radioimmunotherapy and radiotherapy on a human solid tumor in nude mice.

Timing effects of radioimmunotherapy (HIT) combined with external
beam radiotherapy (RT) were assessed In human colon carcinoma xe
nografts. Initially, dose effects offractlonated RT and RIT were evaluated
separately. Then, 30 Gy RT (10 fractions over 12 days) were combined
with three weekly Lv. injections of 200 g@Ci of 131I-labeled anti-carcino
embryonic antigen monoclonal antibodies in four different treatment
schedules. RIT was given either prior to, concurrently, Immediately after,
or 2 weeks after RT administration. The longest regrowth delay (RD) of
105 days was observed in mice treated by concurrent administration of
RT and lilT, whereas the RDs of RT and RIT alone were 34 and 20 days,
respectively. The three sequential combination treatments produced sig
nificantly shorter RDs ranging from 62 to 70 days. The tumor response
represented by the minimal volume (MV) also showed that concurrent
administration of RT and RIT gave the best result, with a mean MV of
4.5% as compared to MVs from 26 to 53% for the three sequential
treatments. The results were confirmed In a second experiment, In which
a RT of 40 Gy was combined with an identical lilT as above (three
injections of 200 g&Ci of ‘31I-labeled monoclonal antibodies). At compa
rable toxicity levels, the maximum tolerated RT or BIT alone gave shorter
RDs and less tumor shrinkage compared to slinultaneous RT+RIT. These
results may be useful for designing clinical protocols ofcombined RIT and
RT.