El. Hanninen et al., INTERLEUKIN-2 BASED HOME THERAPY OF METASTATIC RENAL-CELL CARCINOMA -RISKS AND BENEFITS IN 215 CONSECUTIVE SINGLE INSTITUTION PATIENTS, The Journal of urology, 155(1), 1996, pp. 19-25
Purpose: In 215 consecutive patients with advanced metastatic renal ce
ll carcinoma seen at a single institution the efficacy and tolerance o
f different subcutaneous recombinant interleukin-2 based home therapie
s were assessed. Materials and Methods: Treatment consisted of subcuta
neous recombinant interleukin-2 alone and subcutaneous recombinant int
erleukin-2 in combination with recombinant interferon-alpha 2 with or
without intravenous 5-fluorouracil. Results: Overall objective respons
e rate in 215 patients was 33% (95% confidence interval 26 to 39%). Am
ong 16 patients receiving recombinant interleukin-2 alone there was 1
partial remission (overall response 6%). In 79 patients receiving reco
mbinant interleukin-2 and interferon-alpha 2 in combination 6 complete
and 16 partial remissions occurred (overall response 28%). Of 120 pat
ients receiving a combination of recombinant interleukin-2, recombinan
t interferon-alpha 2 and 5-fluorouracil 13 achieved a complete and 34
a partial remission (overall response 39%). Of all patients 5% achieve
d long-lasting remissions and remain disease-free. Multivariate analys
es identified pretreatment erythrocyte sedimentation rate greater than
70 mm. per hour and lactic dehydrogenase greater than 280 units per l
. as independent prognostic factors of major significance (p less than
or equal to 0.0001) in metastatic renal cell carcinoma. Additionally,
neutrophil count greater than 6,000/mu l., hemoglobin less than 100 g
m./l., extrapulmonary metastases and bone lesions were identified as m
inor (p less than or equal to 0.006) prognostic variables. Patients we
re assigned to 1 of 3 risk categories according to cumulative risk sco
re defined as the function of the sum of all 6 independent variables.
In 116 intermediate risk patients 2-year survival was 65% (median surv
ival not reached after 32 months) with recombinant interleukin-2, reco
mbinant interferon-alpha 2 and 5-fluorouracil, as opposed to 27% 2-yea
r survival (median survival 15 months) with recombinant interleukin-2
and interferon-alpha 2 (p < 0.0001), and 0% (median survival 4.8 month
s) with single agent recombinant interleukin-2. In the majority of pat
ients systemic toxicity of subcutaneous recombinant interleukin-2 base
d protocols was limited to grade 1 or 2 constitutional symptoms, that
is fever, chills, malaise and anorexia, which allowed for outpatient t
herapy. Conclusions: The present outpatient recombinant interleukin-2
triple drug combination protocol was as effective as the most aggressi
ve intravenous recombinant interleukin-2 regimen available. Combinatio
n home therapy eliminated the need for inpatient and/or intensive care
as required for intravenous cytokine administration and, thereby, it
substantially improved the therapeutic index and cost-effectiveness of
recombinant interleukin-2 therapy in metastatic renal cell carcinoma
stratified for risk.