Collection of peripheral blood stem cells following administration of paclitaxel, cyclophosphamide, and filgrastim in patients with breast and ovarian cancer.
OBJECTIVE
To determine the toxicities and efficacy of paclitaxel, cyclophosphamide (Cy), and recombinant human granulocyte-colony stimulating factor (filgrastim) administered for mobilization and collection of peripheral blood stem cells (PBSC) in patients with breast and ovarian cancer.


METHODS
One hundred and forty-one patients with breast (n = 115) or ovarian cancer (n = 26) received paclitaxel 170 mg/m2 and Cy 2 gm/m2 (n = 42) or paclitaxel 200 mg/m2, Cy 3 gm/m2 (n = 99), and filgrastim (6 micrograms/kg/day) followed by collection of PBSC by apheresis.


RESULTS
The 2 dose levels of paclitaxel and Cy tested were well tolerated. The median yield of CD34+ cells from all patients was 6.53 x 10(6)/kg (range, 0.11-51.76) collected with a median of 2 aphereses (range, 1-8). The target dose of 2.5 x 10(6) CD34+ cells/kg was achieved in 85% of patients. The mean daily collection of CD34+ cells was 5.46 x 10(6)/kg for patients receiving 200 mg/m2 of paclitaxel and 3 gm/m2 of Cy as compared to 2.77 for patients receiving the lower doses (p = 0.0005). Increasing the dose of paclitaxel and Cy did not significantly increase the fraction of patients achieving a target dose of 2.5 x 10(6) CD34+ cells/kg (87% vs 81%, p = 0.367) but did increase the fraction achieving a target of 5.0 x 10(6) CD34+ cells/kg (73% vs 45%, p = 0.002). The mean daily collection of CD34+ cells for patients who had received only 1 prior chemotherapy regimen was 6.59 x 10(6)/kg as compared to 3.47 for patients who had received more than 1 prior chemotherapy regimen (p < 0.0001). Prior radiation therapy (p = 0.003) and patient performance status (p = 0.047) were adverse risk factors for achieving a target dose of > or = 2.5 x 10(6) CD34+ cells/kg.


CONCLUSIONS
The combination of paclitaxel, Cy, and filgrastim can be administered with acceptable toxicity, allowing collection of adequate quantities of PBSC from the majority of patients with breast and ovarian cancer. Increasing the doses of paclitaxel and Cy increased the number of CD34+ cells collected and decreased the number of apheresis procedures necessary to collect target cell doses. However, increasing drug doses did not increase the fraction of patients yielding the minimum CD34+ target dose of 2.5 x 10(6)/kg. Collection of PBSC early in the disease course is the best strategy to assure optimal CD34+ cell doses in all patients.
Weaver
C H
CH
Clinical Research Division of Response Oncology, Inc., Memphis, TN, USA.
Schwartzberg
L S
LS
Birch
R
R
Greco
F A
FA
Hainsworth
J
J
Drapkin
R
R
Campos
L
L
Grapski
R
R
Schwerkoske
J
J
Lautersztain
J
J
Hazelton
B
B
Schnell
F
F
Babcock
W
W
Buckner
C D
CD
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001800:Blood Specimen Collection / Q000379:methods*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D011994:Recombinant Proteins
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide; D017239:Paclitaxel; D000069585:Filgrastim