Phase II study of interleukin-2 and 13-cis-retinoic acid as maintenance therapy in metastatic colorectal cancer.
OBJECTIVE
We have previously shown that low-dose interleukin-2 (IL-2) and 13-cis-retinoic acid (13-cis-RA) improved lymphocyte and natural killer (NK) cell count of patients with advanced tumors showing a clinical benefit from chemotherapy. The primary endpoint of this study was to ask whether IL-2 and 13-cis-RA improved (> or =30%) lymphocyte and NK cell count in patients with metastatic colorectal cancer (MCRC) that had a clinical benefit from induction chemotherapy. Secondary endpoint was the evaluation of toxicity, progression-free survival (PFS), and overall survival (OS).


METHODS
Forty patients with MCRC, showing a clinical benefit from chemotherapy, were treated with subcutaneous low-dose IL-2 (1.8 x 10(6) IU) and oral 13-cis-RA (0.5 mg/kg) in order to maintain responses and improve survival through the increase of lymphocyte and NK cells. The biological parameters and the clinical outcome of these patients were compared with those of a control group of patients (80) with a similar disease status, including clinical benefit from chemotherapy.


RESULTS
The most common adverse events were mild cutaneous skin rash and fever. After 4 months and 2 years of biotherapy, a statistically significant improvement was observed in lymphocyte and number of NK cells with respect to baseline values and to controls. After a median follow-up of 36 months, median PFS was 27.8 months, while median OS was 52.9 months.


CONCLUSIONS
These data show that maintenance immunotherapy with low-dose IL-2 and oral 13-cis-RA in patients with MCRC showing a clinical benefit from chemotherapy is feasible, has a low toxicity profile, improves lymphocyte and NK cell count. An improvement in the expected PFS and OS was also observed. A randomized trial is warranted.
Recchia
Francesco
F
Unità operativa di Oncologia, Ospedale Civile di Avezzano, Avezzano, Italy. frecchia1946@libero.it
Saggio
Gaetano
G
Cesta
Alisia
A
Candeloro
Giampiero
G
Di Blasio
Anna
A
Amiconi
Giovanna
G
Lombardo
Marco
M
Nuzzo
Antonio
A
Lalli
Angelo
A
Alesse
Edoardo
E
Necozione
Stefano
S
Rea
Silvio
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000401:mortality; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D015474:Isotretinoin / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000187:drug effects; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis
D007376:Interleukin-2; D015474:Isotretinoin