A phase 2 trial of standard-dose cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and rituximab plus bevacizumab for patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: SWOG 0515.
S0515 was a phase 2 trial to determine whether the addition of bevacizumab to cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) plus rituximab (R-CHOP) would improve progression-free survival (PFS) without adding significant toxicity in patients with newly diagnosed advanced diffuse large B-cell lymphoma. A total of 73 patients were enrolled. For the 64 eligible patients, median age was 68 years, and 60% had International Prognostic Index scores more than or equal to 3. The observed 1- and 2-year PFS estimates were 77% and 69%, respectively. These PFS estimates were not statistically different from the expected PFS for this population if treated with R-CHOP alone. Grade 3 or higher toxicities were observed in 81% of patients, including 2 grade 5 events. The majority of serious toxicities were hematologic but also included 5 patients with gastrointestinal perforations, 4 patients with thrombotic events, and 11 patients who developed grade 2 or 3 left ventricular dysfunction. Higher baseline urine VEGF and plasma VCAM levels correlated with worse PFS and overall survival. In conclusion, the addition of bevacizumab to R-CHOP chemotherapy was not promising in terms of PFS and resulted in increased serious toxicities, especially cardiac and gastrointestinal perforations. This study is registered at www.clinicaltrials.gov as #NCT00121199.
University of Arizona Cancer Center, Tucson, AZ, USA. astopeck@azcc.arizona.edu
Alison T
AT
Stopeck
Joseph M
JM
Unger
Lisa M
LM
Rimsza
Michael
M
LeBlanc
Brent
B
Farnsworth
Maria
M
Iannone
Martha J
MJ
Glenn
Richard I
RI
Fisher
Thomas P
TP
Miller
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000068258:Bevacizumab; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D000069283:Rituximab; D059039:Standard of Care; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; C571759:R-CHOP protocol; D000068258:Bevacizumab; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone