A phase II study of "decrescendo" interleukin-2 plus interferon-alpha-2a in patients with progressive metastatic melanoma after chemotherapy.
BACKGROUND
The authors tested a biotherapy regimen involving recombinant interferon-alpha-2a (rIFN-alpha-2a) and recombinant human interleukin-2 (rhIL-2), given in a "decrescendo" schedule over 5 days, for its activity and toxicity in 21 patients who previously had received chemotherapy for advanced melanoma.


METHODS
Patients (15 men and 6 women) were given intravenous rhIL-2 at a dose of 18 MIU/m(2) over 6 hours, followed by 18 MIU/m(2) over 12 hours, then 18 MIU/m(2) over 24 hours, and finally 4.5 MIU/m(2)/day for 3 consecutive days. rIFN-alpha-2a (10 MIU/m(2)) was given subcutaneously on Days 1-5. Courses were repeated every 4 weeks. Tumor sites were measured every 8 weeks. Toxicity was recorded using National Cancer Institute Common Toxicity Criteria.


RESULTS
No major objective responses were noted. The median number of courses given was two. The median time to progression was 2 months and the median survival was 6 months (range, 2-25 months). However, 2 patients with melanoma involving >/= 2 visceral organs (1 with a high baseline serum lactate dehydrogenase level) and a third with soft tissue metastases achieved durable control of disease and were alive a median of 30+ months later. A fourth patient had a palliative response with reversal of melanosis and a survival of 7 months. This regimen was well tolerated and resulted in no serious long term adverse effects.


CONCLUSIONS
The response rate for this regimen was no greater than 10% with Type I and II errors each not exceeding 10%. Nevertheless, occasional durable control of disease and the nonoverlapping toxicity profile with prior chemotherapy support consideration of this regimen in these patients who have limited second-line treatment options.
Eton
O
O
Department of Melanoma/Sarcoma, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Buzaid
A C
AC
Bedikian
A Y
AY
Smith
T M
TM
Papadopoulos
N E
NE
Ellerhorst
J A
JA
Hibberts
J L
JL
Legha
S S
SS
Benjamin
R S
RS
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001772:Blood Cell Count; D016207:Cytokines / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins; D016879:Salvage Therapy
D016207:Cytokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins