Local/regional recombinant interleukin 2 (rIL-2) immunotherapy of tumors. Intra-arterial continuous infusion of rIL-2 in bladder cancer patients: a phase I study.
We have investigated clinical and immunological effects of two 5-day cycle continuous infusion of four escalating doses (3,000; 30,000; 300,000; 3,000,000 U/m2/day) of intra-arterial (i.a.) rIL-2, in ten patients with superficial (Ta-T1, N0, M0) bladder TCC. Tumor TUR was performed four days after the end of the second IL-2 cycle. No clinical or laboratory toxicity was detected in any but one patient, who developed grade III hypotension and grade III neurological toxicity. Two CR and two PR were observed in patients treated with 30,000 and 300,000 U/m2/day of rIL-2, respectively. Clinical responses lasted 8+, 8+, 4+ and 4+ months, respectively. Two out of ten patients developed recurrences two months after tumor resection. In the peripheral blood, no changes in the percentage of T (CD3+) lymphocytes were observed, while a significant increase of CD3+ CD16+ T cells was found in 6/9 patients. In contrast, NK (CD3- CD16+) cells were augmented only in 2/9 patients. An increase of B lymphocytes (CD19+ cells) and monocytes (CD14+ cells) was also observed in 3/9 and 7/9 patients, respectively. Lymphocyte activation marker expression (CD25, CD71, HLA-DR) increased mainly on T lymphocytes. NK and LAK activities were enhanced in 4/10 patients, while ADCC activity augmented in 2/10 patients. No detectable increased levels of plasmatic lymphokines (gamma-IFN and alpha-TNF) were found. Enhanced CD8+ and CD4+ tumor infiltrating lymphocytes were demonstrated after IL-2 treatment. Moreover, at the tumor site, lymphocytes expressing CD25 and HLA-DR antigens were noted. Tumor infiltrating macrophages were positive for IL-1 alpha, IL-1 beta and alpha-TNF.
Velotti
F
F
Dipartimento di Medicina Sperimentale, Università degli Studi La Sapienza, Rome, Italy.
Tubaro
A
A
Stoppacciaro
A
A
Pettinato
A
A
Morrone
S
S
Bossola
P
P
Napolitano
T
T
Miano
L
L
Ruco
L
L
Piccoli
M
M
D000328:Adult; D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000628:therapy*; D004341:Drug Evaluation; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D007261:Infusions, Intra-Arterial; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D001749:Urinary Bladder Neoplasms / Q000628:therapy*
D007155:Immunologic Factors; D007376:Interleukin-2; D011994:Recombinant Proteins