Interleukin-2, interferon-alpha and medroxyprogesterone acetate in metastatic renal cell carcinoma.
BACKGROUND
Interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) are the main immuno-biological agents used in the therapy of metastatic renal cell carcinoma (RCC). Unfortunately the promising results obtained in biological studies have not yet been confirmed in clinical studies. One reason is linked to the immunosuppression of metastatic patients which is caused by macrophage products. IL-6 in particular is considered a growth factor for RCC. Medroxyprogesterone acetate (MPA) may interfere with IL-6 macrophage production, possibly causing a synergistic effect in association with IL-2 and IFN-alpha. Therefore the purpose of our study was to evaluate the toxicity and the efficacy of the association between IL-2, IFN-alpha and MPA.


METHODS
Forty-two consecutive patients with metastatic RCC were enrolled. IL-2 was administered subcutaneously at doses of 4.5 million UI on days 1-5, 8-12, 15-19 and 22-26; IFN-alpha was administered s.c. at a dose of 3 million t.t.w; MPA was administered orally at a dose of 1000 mg daily. This schedule was repeated after a rest of 2 weeks.


RESULTS
Toxicity was mild: the main symptoms observed were fatigue and fever. Six CR (14%), five PR (12%), thirteen SD (31%) and seventeen PD (41%) were observed for an overall response rate of 26%. Patients with good PS and low levels of CRP had a better prognosis.


CONCLUSIONS
Considering both the good activity and the low toxicity of this scheme, we think that it could be carried out in normal clinical practice.
Naglieri
Emanuele
E
Medical and Experimental Oncology Department, Oncology Institute, Via Amendola 209, 70126 Bari, Italy. onmes2@libero.it
Lopez
Massimo
M
Lelli
Giorgio
G
Morelli
Francesco
F
Amodio
Antonella
A
Di Tonno
Pasquale
P
Gebbia
Nicola
N
Di Seri
Marisa
M
Chetri
Maria Concetta
MC
Rizzo
Pietro
P
Abbate
Ines
I
Casamassima
Addolorata
A
Selvaggi
Francesco Paolo
FP
Colucci
Giuseppe
G
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects; D015850:Interleukin-6 / Q000097:blood; D007680:Kidney Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins; D015996:Survival Rate
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D015850:Interleukin-6; D011994:Recombinant Proteins; D002097:C-Reactive Protein; D017258:Medroxyprogesterone Acetate