Phase III intergroup study of fludarabine phosphate compared with cyclophosphamide, vincristine, and prednisone chemotherapy in newly diagnosed patients with stage III and IV low-grade malignant Non-Hodgkin's lymphoma.
OBJECTIVE
To compare the efficacy and safety of fludarabine phosphate with cyclophosphamide, vincristine, and prednisone (CVP) in 381 previously untreated, advanced-stage, low-grade (lg) non-Hodgkin's lymphoma (NHL) patients in a phase III, multicenter study.


METHODS
Between 1993 and 1997, patients were randomly assigned to treatment with either fludarabine (25 mg/m2 intravenously [IV] daily for 5 days every 4 weeks) or CVP (cyclophosphamide 750 mg/m2 IV on day 1; vincristine, 1.4 mg/m2 IV on day 1; and prednisone, 40 mg/m2 orally on days 1 through 5 every 4 weeks). Results Overall response (OR) rates were significantly improved in the fludarabine arm versus the CVP arm, both for the intent-to-treat (ITT) population and assessable patients (P < .001). Complete response (CR) rates in the ITT population were also higher after fludarabine treatment. The CR rate was 38.6% for fludarabine compared with 15.0% for CVP. There were no statistically significant differences in time to progression (TTP), time to treatment failure (TTF), and overall survival (OS) between treatment groups. WHO grades 3 and 4 hematologic adverse events were more common in the fludarabine arm. However, concerning the higher incidence of granulocytopenia, this did not translate to more infections in fludarabine-treated patients.


CONCLUSIONS
Newly diagnosed lgNHL patients who received fludarabine achieved higher OR and CR rates compared with CVP-treated patients. No differences in TTP, TTF, and OS were noted. Fludarabine is a highly active single agent in lgNHL. Combination therapies incorporating fludarabine are now being further evaluated as first-line therapy in follicular NHL.
Hagenbeek
Anton
A
European Organisation for Research and Treatment of Cancer (EORTC) Lymphoma Group, Amsterdam, The Netherlands. a.hagenbeek@amc.uva.nl
Eghbali
Houchingue
H
Monfardini
Silvio
S
Vitolo
Umberto
U
Hoskin
Peter J
PJ
de Wolf-Peeters
Christiane
C
MacLennan
Ken
K
Staab-Renner
Elvira
E
Kalmus
Joachim
J
Schott
Astrid
A
Teodorovic
Ivana
I
Negrouk
Anastassia
A
van Glabbeke
Martine
M
Marcus
Robert
R
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011241:Prednisone / Q000627:therapeutic use; D011446:Prospective Studies; D001084:Vidarabine Phosphate / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014750:Vincristine / Q000627:therapeutic use
D000964:Antimetabolites, Antineoplastic; D001084:Vidarabine Phosphate; C042382:fludarabine phosphate; D014750:Vincristine; D003520:Cyclophosphamide; D011241:Prednisone