Phase II trial of CHOP chemotherapy followed by tositumomab/iodine I-131 tositumomab for previously untreated follicular non-Hodgkin's lymphoma: five-year follow-up of Southwest Oncology Group Protocol S9911.
OBJECTIVE
Advanced follicular lymphoma (FL) is incurable with conventional chemotherapy and radiotherapy, and optimal front-line management is controversial. This study was performed to determine the efficacy of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy followed by tositumomab/iodine I-131 tositumomab.


METHODS
From 1999 to 2000, the Southwest Oncology Group (SWOG) conducted a phase II trial (S9911) to test a novel new regimen consisting of six cycles of CHOP chemotherapy followed 4 to 8 weeks later by tositumomab/iodine I-131 tositumomab in 90 eligible patients with previously untreated, advanced-stage FL.


RESULTS
The overall response rate was 91%, including a 69% complete remission (CR) rate. After a median follow-up time of 5.1 years, the estimated 5-year overall survival (OS) rate was 87%, and the progression-free survival (PFS) rate was 67%. The 5-year estimates of OS and PFS were each 23% better (absolute difference) than the corresponding figures for patients treated on previous SWOG protocols with CHOP alone. An analysis according to the Follicular Lymphoma International Prognostic Index showed that 21% of patients had high-risk features, 44% had intermediate-risk features, and 34% had low-risk features. High-risk patients had worse OS than lower risk patients (P = .05), but differences in PFS were not statistically significant (P = .21). Serial monitoring of the t(14;18) translocation in bone marrow by polymerase chain reaction demonstrated that 32 of 38 informative patients obtained molecular CRs, including seven patients (18%) after CHOP and 24 additional patients (63%) after tositumomab/iodine I-131 tositumomab. (The timing of conversion of one patient was unclear.)


CONCLUSIONS
A prospective, phase III, randomized Intergroup Trial is currently underway comparing the efficacy of the promising CHOP + tositumomab/iodine I-131 tositumomab regimen with the efficacy of CHOP + rituximab.
Press
Oliver W
OW
Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Unger
Joseph M
JM
Braziel
Rita M
RM
Maloney
David G
DG
Miller
Thomas P
TP
Leblanc
Michael
M
Fisher
Richard I
RI
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D018951:Antigens, CD20 / Q000032:analysis*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011241:Prednisone / Q000008:administration & dosage; D016499:Radioimmunotherapy / Q000379:methods; D016019:Survival Analysis; D016896:Treatment Outcome; D014481:United States; D014750:Vincristine / Q000008:administration & dosage
D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; C119496:tositumomab I-131; D011241:Prednisone