b) Grade 3 toxicity and Grade 4 granulocytopenia and thrombocytopenia: 
Treatment will be withheld until the toxic reaction improves to < Grade 
1 or symptoms return to baseline. If the reaction does not resolve to 
either < Grade 1 or symptoms return to baseline within four weeks, then 
the subject will be removed from the study. If the toxicity resolves to 
< Grade 1 or symptoms return to baseline, then subjects who have not 
previously had their dose of rIL-2 attenuated as described above, may 
resume therapy at 2 x 10 6 U/m 2 /day rIL-2 and 6 x 10 6 U/m 2 /day rIL-2 and 
3 x 10 6 U/m 2 /day IFNaA. Subjects experiencing a recurrent Grade 3 
toxicity or Grade 4 granulocytopenia and thrombocytopenia at this lowest 
level will be discontinued from the study. If a different Grade 3 toxicity 
occurs at this lowest dose level then therapy will be withheld until the 
toxicity reaction returns to baseline or < Grade 1 . Treatment can then be 
resumed at the same dose level at the Investigator’s discretion. If toxicity 
does not resolve by the end of four weeks, the subject will be discontinued 
from the study. Subjects experiencing Grade 3 neutotoxicity or cardiac 
toxicity and subjects requiring prolonged use of pressors ( > 48 consecutive 
hours) for the management of hypotension will be withdrawn from the 
study. 
c) Grade 4 Toxicity: Treatment will be stopped and the subject withdrawn 
from the study, except for Grade 4 granulocytopenia and 
thrombocytopenia. Doses of rIL-2 and IFNoA will be modified for these 
toxicities 
10.5 TIL Toxicity 
All toxicity will be graded according to Appendix III. Previously unknown or 
severe toxicities must be reported as adverse experiences. 
a) Animal Studies: No measurable toxicity was reported in the adoptive 
transfer of rIL-2 activated TIL with cyclophosphamide and rIL-2 to mice 
bearing metastases from various types of tumors 14 . 
b) Human Studies: rIL-2 has been used in clinical studies with TIL in the 
treatment of metastatic cancer. The NCI pilot study 7 on 12 study subjects 
with metastatic cancer examined the effect of 6 x 10 10 TIL. Up to four 
infusions of rIL-2 activated TIL were administered over a period of 2 to 
4 days and rIL-2 was given at 10,000, 30,000 and 100,000 U/kg every 
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