Randomized, double-blind, placebo-controlled trial to evaluate the hematopoietic growth factor PIXY321 after moderate-dose fluorouracil, doxorubicin,and cyclophosphamide in stage II and III breast cancer
Se. Jones et al., Randomized, double-blind, placebo-controlled trial to evaluate the hematopoietic growth factor PIXY321 after moderate-dose fluorouracil, doxorubicin,and cyclophosphamide in stage II and III breast cancer, J CL ONCOL, 17(10), 1999, pp. 3025-3032
Purpose: To measure the effect of PIXY321 (granulocyte-macrophage colony-st
imulating factor/interleukin-3 S. cerevisiae fusion protein) on the inciden
ce, duration, and complications of neutropenia and thrombacytopenia after m
oderate-dose fluorouracil 600 mg/m(2), doxarubicin 60 mg/m(2), and cyclopho
sphamide 750 mg/m(2) (FAC) chemotherapy in patients with stage II and III b
reast cancer.
Patients and Methods: In this multicenter, randomized, double-blind placebo
-controlled trial, 71 women were to receive four 21-day cycles of treatment
with moderate-dose FAC chemotherapy by short intravenous infusion on day 1
, followed by either placebo or PIXY321 (375 mu g/m(2) subcutaneously twice
a day) on days 3 to 15, All patients were to receive prophylactic oral cip
rofloxacin when the absolute neutrophil count was less than 1,000/mu L.
Results: PIXY321 significantly reduced the incidence and duration of grade
3 and grade 4 neutropenia in cycles 1 and 2 and the duration of grade 3 neu
tropenia in cycles 1 through 4. In cycles 3 and 4, grade 3 thrombocytopenia
was significantly more common with PIXY321 (P < .05), Two patients, both i
n the PIXY321 group, required platelet transfusions. Fever and hospitalizat
ion for intravenous antibiotics were significantly more common in the PIXY3
21 group during cycle 1 only. More patients in the PIXY321 group achieved h
ematologic recovery by day 22 in cycles 1 through 3, and time to recovery w
ets significantly shorter with PIXY321 in all cycles. FAC dose intensity wa
s roughly 2% higher in the PIXY321 group (P = NS). Nonhematologic events of
any intensity occurring with significantly greater overall frequency in th
e PIXY321 group included injection-site reactions, fever, chills, abdominal
pain, and arthralgia. No patient died on study or within 30 days of her la
st dose of study drug.
Conclusion: PIXY321 decreased the incidence and duration of FAG-induced gra
de 3 and 4 neutropenia in cycles 1 and 2 and significantly shortened the ti
me to hematologic recovery in all cycles. However, if produced more systemi
c toxicity as well as thrombocytopenia in cycles 3 and 4. (C) 1999 by Ameri
can Society of Clinical Oncology.