Immunotherapy (recombinant interleukin 2), hormone therapy (medroxyprogesterone acetate) and antioxidant agents as combined maintenance treatment of responders to previous chemotherapy
G. Mantovani et al., Immunotherapy (recombinant interleukin 2), hormone therapy (medroxyprogesterone acetate) and antioxidant agents as combined maintenance treatment of responders to previous chemotherapy, INT J ONCOL, 18(2), 2001, pp. 383-391
An open, non-randomized phase II study was carried out including all patien
ts treated with whatever chemotherapy or combined modality regimen for what
ever cancer who were in clinical objective response or stable disease (SD)
for more than three months, to receive maintenance treatment with recombina
nt interleukin-2 (rIL-2) plus medroxyprogesterone acetate (MPA) plus antiox
idant agents alpha-lipoic acid (ALA) and N-acetyl cysteine (NAC). The main
study endpoints were clinical outcome and toxicity. The secondary endpoints
were effects of treatment on cancer-related anorexia/cachexia syndrome (CA
CS) symptoms, on serum levels of proinflammatory cytokines, IL-2, C-reactiv
e protein (CRP) and leptin as well as the evaluation of quality of life (QL
). rIL-2 was administered at a dose of 1.8 MIU subcutaneously three times/w
eek on alternate days for the first two weeks of every month and MPA was gi
ven orally at a dose of 500 mg once a day at alternate days without interru
ption. ALA 300 mg/day orally and NAC 1800 mg/day orally were also administe
red. The treatment was administered until progression of disease or appeara
nce of toxicity. From July 1998 to May 2000, 16 patients were enrolled in t
he study (M/F ratio: 15/1; mean age: 62 years, range 45-71). The median dur
ation of maintenance treatment was 10 months (range 5-22). The response to
maintenance treatment at September 2000 was: CR (persistent throughout the
treatment) 4 patients (25%); SD 1 patient (6.2%); PD II patients (68.8%). T
he median duration of response was 9.8 months (range: 5-22+). The median fo
llow-up duration was 19 months (range: 8-102). The median OS was not reache
d. The median PFS was 14 months (range 1-29). The 1-year survival rate was
25%. At September 2000, 9 patients are still surviving. No grade 3/4 toxici
ty was observed. One Grade 2 skin toxicity was observed and Grade 1: 2 feve
r, 2 thrombocytopenia, 1 neutropenia and 1 skin were observed. The ECOG PS
did worsen significantly, the body weight and BMI increased significantly a
fter treatment, whereas the appetite did not change significantly. The QL e
valuation showed a significant amelioration of cognitive functions and a bo
rderline significant amelioration of emotional functions after treatment, w
hereas a borderline worsening of dyspnea was observed. The absolute lymphoc
yte count increased significantly after the maintenance treatment, as well
as the serum IL-2, TNF alpha decreased at borderline statistical significan
ce; the serum levels of leptin did not change significantly. The evaluation
of patient subgroups showed that responders/survivors had a pattern superi
mposable to that of whole patient population, the patients who rapidly prog
ressed and died exhibited no significant changes of these parameters during
treatment. The results of the present study suggest that the host immune r
esponse, evaluated by several parameters, after IL-2 administration, (e.g.
lymphocytosis), are worth further study as potential markers for the major
end points of cancer treatment, i.e. OS and QL, in an adequate number of pa
tients.