1917
document
Granulocyte-macrophage colony-stimulating factor treatment before doxorubicin and cyclophosphamide chemotherapy priming in women with early-stage breast cancer . PURPOSE To determine if inhibition of stem-cell activity induced by granulocyte-macrophage colony-stimulating factor ( [ GM-CSF ] ; Sargramostim ; Immunex Corporation , Seattle , WA ) withdrawal or priming protects hematopoietic stem cells from the cytotoxic effects of adjuvant chemotherapy for early-stage breast cancer . PATIENTS AND METHODS Serial blood counts were performed in 20 women with early-stage breast cancer receiving four courses of cyclophosphamide and doxorubicin chemotherapy . By a double-blind , placebo-controlled , balanced randomization , subjects received GM-CSF priming on days 5 to 1 for courses 1 and 3 or courses 2 and 4 . RESULTS Compared with before priming , after priming the times to neutrophil nadir ( 12.8 +/- 2.5 days v 14.8 +/- 1.5 days , respectively ; P =.0001 ) and platelet nadir ( mean +/- SD , 10.1 +/- 1.9 days v 11.1 +/- 2.2 days , P < .05 ) were shorter , indicating a shift of cytotoxicity to later progenitors . The neutrophil nadir was similar with and without priming ( mean +/- SD , 490 +/- 310/microL v 550 +/- 350/microL , respectively ; P =.2 ) ; however , on day 16 the mean neutrophil count was higher ( mean +/- SD , 1030 +/- 580/microL v 690 +/- 370/microL , P =.004 ) , and the proportion of patients with a neutrophil count less than 500/microL was lower after priming than before ( six of 35 or 17 . 1 % v 12 of 34 or 35.3 % , respectively ; P =.04 ) . The platelet nadir was higher ( mean +/- SD , 166,000 +/- 51,000/microL after priming v 151,000 +/- 45,000/microL before priming , P =.007 ) , and the duration of thrombocytopenia , ie , a platelet count less than 150,000/microL , was shorter ( 1.5 +/- 2.1 days v 2.8 +/- 2.9 days , P =.0025 ) after priming . Episodes of fever and neutropenia were not observed . CONCLUSIONS GM-CSF priming from days 5 to 1 before doxorubicin and cyclophosphamide chemotherapy was associated with an earlier neutrophil and platelet nadir . On day 16 , a higher mean neutrophil count and a lower proportion of patients with severe ( < 500/microL ) neutropenia were observed . Beneficial effects on the severity and duration of thrombocytopenia were also noted . These observations support the hypothesis that GM-CSF priming protects hematopoietic progenitors from the cytotoxic effects of chemotherapy .
1918
Intervention_Pharmacological
Granulocyte-macrophage colony-stimulating factor treatment
1919
Intervention_Pharmacological
granulocyte-macrophage colony-stimulating factor
1920
Intervention_Pharmacological
four courses of cyclophosphamide and doxorubicin chemotherapy .
1921
Intervention_Pharmacological
subjects received GM-CSF priming on days 5 to 1 for courses 1 and 3 or courses 2 and 4
1922
Intervention_Pharmacological
chemotherapy
1923
Outcome_Physical
times to neutrophil nadir
1924
Outcome_Physical
platelet nadir
1925
Outcome_Physical
neutrophil nadir
1926
Outcome_Physical
neutrophil count
1927
Outcome_Physical
neutrophil count
1928
Outcome_Physical
platelet nadir
1929
Outcome_Physical
duration of thrombocytopenia
1930
Outcome_Adverse-effects
fever and neutropenia
1931
Outcome_Physical
neutrophil
1932
Outcome_Physical
platelet nadir
1933
Outcome_Physical
neutrophil count
1934
Outcome_Adverse-effects
neutropenia
1935
Outcome_Physical
thrombocytopenia
1936
Participant_Condition
women with early-stage breast cancer .
1937
Participant_Condition
early-stage breast cancer .