Improvement of overall and failure-free survival in stage IV follicular lymphoma: 25 years of treatment experience at The University of Texas M.D. Anderson Cancer Center.
OBJECTIVE
Advanced-stage follicular lymphoma is considered incurable. The pace of improvements in treatment has been slow. This article analyzes five sequential cohorts of patients with stage IV follicular lymphoma treated between 1972 and 2002.


METHODS
Five consecutive studies (two were randomized trials) involving 580 patients were analyzed for overall survival (OS), failure-free survival (FFS), and survival after first relapse. A proportional hazards analysis, and subset analyses using the follicular lymphoma international prognostic index (FLIPI) score were performed. Treatment regimens included: cyclophosphamide, doxorubicin, vincristine, prednisone, bleomycin (CHOP-Bleo); CHOP-Bleo followed by interferon alfa (IFN-alpha); a rotation of three regimens (alternating triple therapy), followed by IFN-alpha; fludarabine, mitoxantrone, dexamethasone (FND) followed by IFN-alpha; and FND plus delayed versus concurrent rituximab followed by IFN-alpha.


RESULTS
Improvements in 5-year OS (from 64% to 95%) and FFS (from 29% to 60%) indicate steady progress, perhaps partly due to more effective salvage therapies, but the FFS data also indicate improved front-line therapies; these observations held true after controlling for differences in prognostic factors among the cohorts. The FLIPI model adds rigor to and facilitates comparisons among the different cohorts. An unexpected finding in this study was a trend toward an apparent FFS plateau.


CONCLUSIONS
Evolving therapy, including the incorporation of biologic agents, has led to stepwise significant outcome improvements for patients with advanced-stage follicular lymphoma. The apparent plateau in the FFS curve, starting approximately 8 to 10 years from the beginning of treatment, raises the issue of the potential curability of these patients.
Department of Lymphoma/Myeloma, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Qi
Q
Liu
Luis
L
Fayad
Fernando
F
Cabanillas
Fredrick B
FB
Hagemeister
Gregory D
GD
Ayers
Mark
M
Hess
Jorge
J
Romaguera
M Alma
MA
Rodriguez
Apostolia M
AM
Tsimberidou
Srdan
S
Verstovsek
Anas
A
Younes
Barbara
B
Pro
Ming-Sheng
MS
Lee
Ana
A
Ayala
Peter
P
McLaughlin
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016016:Proportional Hazards Models