Adjuvant interferon therapy for patients with uveal melanoma at high risk of metastasis.
OBJECTIVE
To examine whether interferon (IFN)-alfa-2a treatment after radiation or enucleation reduces death rates in patients with uveal melanoma.


METHODS
Interventional, comparative case series.


METHODS
Subjects were identified through the ocular oncology clinic of the Massachusetts Eye and Ear Infirmary. Patients eligible for the study were at increased risk of metastasis because of the presence of at least one of the following characteristics: age >or=65 years, largest tumor diameter (LTD) >or=15 mm, ciliary body involvement of the tumor, or extrascleral tumor extension.


METHODS
Between May 1995 and June 1999, 121 patients with choroidal or ciliary body melanoma began a 2-year course of therapy (3 MIU IFN-alfa-2a subcutaneously 3 times per week), initiated within 3 years of primary therapy. All patients underwent regular monitoring for drug toxicity. To evaluate IFN-alfa-2a efficacy, we selected a series of historical controls frequency-matched (2:1) to IFN-alfa-2a-treated patients on age (+/-5 years), LTD (+/-3 mm), gender, and survival time between primary therapy and initiation of IFN therapy. Survival status was ascertained for all patients through December 2006.


METHODS
Melanoma-related mortality, metastasis, IFN-related toxicities.


RESULTS
Fifty-five patients (45%) completed therapy; the median dose for IFN-alfa-2a-treated patients was 792 MIU (85% of the theoretic dose). The median follow-up time in the IFN-alfa-2a-treated group was approximately 9 years. Treatment and control groups were similar with respect to age (P = 0.78), LTD (P = 0.38), and gender (P = 1.0). Of 363 patients, 108 developed metastasis under observation; 42 of these were IFN-alfa-2a-treated patients. Cumulative 5-year melanoma-related death rates were 17% in the radiation or enucleation-only group, 15% in those who completed the entire IFN-alfa-2a course, and 35% in those who discontinued IFN-alfa-2a therapy. In multivariate Cox regression, IFN-alfa-2a had no significant influence on melanoma-related mortality (rate ratio = 1.02, 95% confidence interval, 0.68-1.5, P = 0.91) or all-cause mortality (rate ratio = 0.84, 95% confidence interval, 0.58-1.2, P = 0.34).


CONCLUSIONS
Interferon-alfa-2a has no material influence on survival in patients with choroidal melanoma.
Lane
Anne Marie
AM
Retina Service, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02114, USA. alane@meei.harvard.edu
Egan
Kathleen M
KM
Harmon
David
D
Holbrook
Amy
A
Munzenrider
John E
JE
Gragoudas
Evangelos S
ES
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D015353:Eye Enucleation; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018714:Radiotherapy, Adjuvant; D011994:Recombinant Proteins; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome; D014604:Uveal Neoplasms / Q000188:drug therapy* / Q000401:mortality
D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins