Analysis of long-term outcomes of combined modality therapy for cutaneous T-cell lymphoma.
BACKGROUND
Although cutaneous T-cell lymphoma (CTCL), including mycosis fungoides (MF) and Sézary syndrome, is often responsive to treatment, few current therapies increase survival or consistently induce durable remissions, especially in advanced disease.


OBJECTIVE
In an effort to improve treatment efficacy and outcome in CTCL, a combined modality protocol using 3 to 4 consecutive phases of therapy was initiated in 1987 at M.D. Anderson Cancer Center, Houston, Tex.


METHODS
During a period of 15 years between 1987 and 2001, 95 patients with early-stage (Ia-IIa, n = 50) and late-stage (IIb-IVb, n = 45) MF were treated with subcutaneous interferon-alpha and oral isotretinoin, followed by total-skin electron beam therapy, and long-term maintenance therapy with topical nitrogen mustard and interferon-alpha. Patients with late-stage (IIb-IVb) disease also received 6 cycles of combination chemotherapy before electron beam therapy.


RESULTS
Combined modality therapy yielded a response rate of 85% with a 60% complete response rate. Among 38 patients with early-stage disease and 18 patients with late-stage disease achieving complete response, 9 (24%) patients with early-stage MF and 3 (17%) patients with late-stage MF achieved sustained remissions lasting more than 5 years. The median disease-free survival (DFS) for early and late stages of disease was 62 and 7 months, with 5-year Kaplan-Meier estimated rates of 50% and 27%, respectively. Current median overall survival times on combined modality are 145 months for patients with early-stage disease and 36 months for those with late-stage disease. Death was attributable to CTCL disease in 17 (55%) of 31 cases. The Kaplan-Meier estimates for 5-year survival are 94% for early-stage and 35% for late-stage disease. Univariate survival analysis in this patient population reveals statistically significant associations of clinical stage with overall response rates (P =.02), DFS (P =.03), and overall survival (P <.0001); age with DFS (P =.001) and overall survival (P =.04); and T stage (P <.0001) and lactate dehydrogenase (P =.007) with overall survival. By multivariate analysis using a Cox proportional hazards model, only age was significantly associated with DFS (hazard ratio 2.9), and only stage with overall survival (hazard ratio 18.2).


CONCLUSIONS
This nonrandomized and uncontrolled CTCL study gives supportive evidence that this multiphased combined modality regimen is well tolerated and may yield higher response rates and DFS than total-skin electron beam therapy alone, but provides no evidence for a change in survival.
Duvic
Madeleine
M
Division of Internal Medicine, Department of Dermatology, University of Texas M. D. Anderson Cancer Center, Houston 77030-4095, USA.
Apisarnthanarax
Narin
N
Cohen
Deborah S
DS
Smith
Terry L
TL
Ha
Chul S
CS
Kurzrock
Razelle
R
D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D015474:Isotretinoin / Q000627:therapeutic use*; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis; D016896:Treatment Outcome
D016898:Interferon-alpha; D015474:Isotretinoin