4. Cytokines 
a. Interleukin-2 . The recombinant IL-2 used in this trial will be provided by 
the Division of Cancer Treatment, National Cancer Institute (supplied by the 
Cetus Corporation, Emeryville, CA) . The IL-2 will be provided as a lyophilized 
powder and will be reconstituted with 1,2 ml/vial. Each vial contains 
approximately 1.2 mg of IL-2 (specific activity 18 x 10° lU/mg) . Less than 0.04 
ng of endotoxin are present per vial as measured by the limulus amebocyte assay. 
Each vial also contains 5% mannitol and approximately 130 - 230 ug of sodium 
dodecyl sulfate/mg of IL-2, Following reconstitution the IL-2 will be diluted 
in 15 ml of D 5 W and will be infused intravenously as a dose of 720,000 lU/kg over 
a 15 minute period every 8 hr prior to the IL-4. For patients receiving TIL, 
cytokines will begin from two to 24 hr after the TIL infusion. IL-2 and IL-4 
will be given for up to five consecutive days as tolerated. Under no 
circumstances will more than 15 doses of IL-2 or IL-4 be administered. The same 
toxicity criteria will be used as in our previous protocol (86-C-183c), as 
detailed in Appendix B.. Doses may be skipped depending on patient tolerance. 
Doses will be skipped if patients reach grade III or grade IV toxicity. If this 
toxicity is easily reversed by supportive measures then additional doses may be 
given. 
b. Interleukin-4 . Recombinant IL-4 is supplied by Sterling Drug Inc, (Malvern, 
PA) . It is diluted in 20 ml of normal saline containing a final concentration 
of 0.25% normal human serum albumin. One vial containing 100 ug of IL-4 was 
noted to have 1,5 x 10^ units of activity in a biologic assay perfomed at Immunex 
(Seattle, WA) . Both IL-2 and IL-4 will be infused sequentially, giving the IL-2 
first intravenously over no longer than 15 minutes using an infusion pump. 
5, Dose Modification . Dose modification is based on the table presented in 
Appendix B. 
Constitutional symptoms : Fever and arthritis: If Grade 3 or 4 toxicity 
occurs patients will have a dose interruption. Treatment will commence again 
following improvement of toxicity to level 1 or 2. No dose modification will 
take place unless Grade 3 or 4 toxicity occurs on subsequent cycles. 
Hematology and coagulation toxicity : Patients developing Grade 4 
hematology and coagulation toxicity during therapy will have treatment 
interruption. When hematology and coagulation toxicity returns to < 2 , therapy 
may be reinstituted at the same dosage level. If Grade 4 hematology and 
coagulation toxicity continues at these doses, then the dose of IL-2 will be 
reduced. Patients will be removed from study for persistent or recurrent Grade 
4 toxicity. 
Infection or hemorrhage : Patients developing Grade 3 or greater infectious 
or hemorrhagic toxicity during therapy will have treatment interruption. When 
toxicity returns to < 2, treatment can be continued. If Grade 3 or greater 
toxicity recurs, then the dose of IL-2 will be reduced by 50%. Patients will be 
removed from study for persistent or recurrent Grade 3 or greater toxicity. 
Other gastrointestinal toxicity : Patients developing Grade 3 or worse GI 
toxicity during therapy will have treatment interruption. When GI toxicity 
returns to < 2 , treatment will be continued at the same dosage level. If Grade 
3 or worse GI toxicity continues, then the dose of IL-2 will be reduced by 50%. 
Patients will be removed from study for persistent or recurrent Grade 3 or worse 
toxicity at the 50% dose of IL-2. 
Renal toxicity : Patients developing Grade 4 or worse renal toxicity during 
therapy will have treatment interruption. When renal toxicty returns to < 2 , 
therapy will be continued at the same dosage level. If Grade 4 or worse renal 
toxicity continues at this dose, then the dose of IL-2 will be reduced by 50%. 
Patients will be removed from study for persistent or recurrent Grade 4 or worse 
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Recombinant DNA Research, Volume 14 
