Clinical efficacy of cancer subcutaneous immunotherapy with interleukin-2 in relation to the pretreatment levels of tumor growth factor insulin-like growth factor-1.
OBJECTIVE
IGF-1 has been proven to be one of the most important growth factors for normal and neoplastic cells. Abnormally high levels of IGF-1 have been observed in cancer patients. Since it has been demonstrated that some growth factors may counteract the action of antitumor cytokines, the presence of increased IGF-1 concentrations could reduce the efficacy of cancer biotherapies with cytokines, such as IL-2. The present study was performed to evaluate the efficacy of IL-2 immunotherapy in relation to the pretreatment levels of IGF-1 in advanced cancer patients.


METHODS
The study included 20 consecutive patients with metastatic renal cell cancer who were treated subcutaneously with IL-2 at 6 million IU/day for 5 days/week for 6 weeks. IGF-1 serum levels were measured by RIA on venous blood samples collected before the immunotherapy, after 3 weeks, and at the end of IL-2 injection.


RESULTS
Objective tumor regressions were obtained in 5/20 patients, consisting of 1 complete response (CR) and 4 partial responses (PR). Nine patients had stable disease and the last 6 patients progressed. Abnormally high pretreatment levels of IGF-1 were seen in 13/20 patients. The percent of clinical responses (CR + PR) was significantly higher in patients with normal pretreatment concentrations of IGF-1 than in those with elevated levels (4/7 vs 1/13, P < 0.01). No significant changes in mean IGF-1 levels occurred during IL-2 therapy. However, mean IGF-1 levels increased in progressing patients and decreased in those with a response or stable disease, even though none of the differences was statistically significant.


CONCLUSIONS
The study showed that high pretreatment levels of IGF-1 are associated with a reduced efficacy of IL-2 immunotherapy of renal cancer. Further studies are required to establish whether IGF-1 levels simply reflect the extension of disease, or whether they may influence per se the action of IL-2.
Divisione di Radioterapia Oncologica, Ospedale San Gerardo, Monza, Milano, Italy.
P
P
Lissoni
S
S
Barni
A
A
Ardizzoia
F
F
Frigerio
F
F
Paolorossi
M
M
Cazzaniga
G
G
Tancini
F
F
Rocco
M
M
Aapro
D000704:Analysis of Variance; D002292:Carcinoma, Renal Cell / Q000097:blood* / Q000556:secondary / Q000628:therapy*; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007376:Interleukin-2 / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000097:blood* / Q000473:pathology / Q000628:therapy*; D008297:Male; D011863:Radioimmunoassay; D016896:Treatment Outcome
D007376:Interleukin-2; D007334:Insulin-Like Growth Factor I