Combination of fludarabine and mitoxantrone in untreated stages III and IV low-grade lymphoma: S9501.
OBJECTIVE
To determine the efficacy of combination fludarabine and mitoxantrone (FN) in untreated stages III and IV low-grade lymphoma. The major end point was to estimate progression-free survival (PFS) in all eligible patients.


METHODS
Seventy-eight eligible patients were registered. Chemotherapy courses were administered every 4 weeks with mitoxantrone 10 mg/m2 on day 1 and fludarabine 25 mg/m2 on days 1, 2, and 3 for a total of six to eight cycles. Pneumocystis carinii prophylaxis was required.


RESULTS
Seventy-three patients (94%) attained an objective response. Complete remission was demonstrated in 34 patients (44%) and partial remission was demonstrated in 39 patients (50%). With a median follow-up time of 5.5 years, the median PFS was 32 months, with a 4-year PFS rate of 38%. Median survival has not been reached and 88% of all patients are alive at 4 years. The application of the International Prognostic Index and serologic staging showed significant differences in PFS in all risk groups, whereas overall survival was markedly worse for the highest-risk group in either prognostic model. Three prior Southwest Oncology Group trials using a regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone or a combination of prednisone, vincristine, methotrexate, cytarabine, cyclophosphamide, etoposide, nitrogen mustard, vincristine, procarbazine, and prednisone in similar patient populations demonstrated comparable clinical outcome, although the 4-year survival for FN was better. FN was well tolerated, but mild to severe reversible myelosuppression was noted. Other complications were rare.


CONCLUSIONS
FN is an effective, safe chemotherapy combination for patients with advanced-stage, low-grade lymphoma. Clinical outcomes were comparable to prior published data using anthracycline-based regimens.
Velasquez
William S
WS
University of Texas Medical Branch, Galveston, USA. william.velasquez@usoncology.com
Lew
Danika
D
Grogan
Thomas M
TM
Spiridonidis
C Harris
CH
Balcerzak
Stanley P
SP
Dakhil
Shaker R
SR
Miller
Thomas P
TP
Lanier
Keith S
KS
Chapman
Robert A
RA
Fisher
Richard I
RI
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009367:Neoplasm Staging; D016019:Survival Analysis; D016896:Treatment Outcome; D014481:United States; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
D008942:Mitoxantrone; D014740:Vidarabine; C024352:fludarabine