Phase I/II study of PIXY321 in combination with cyclophosphamide and carboplatin in the treatment of ovarian cancer.
OBJECTIVE
Our purpose was to evaluate the safety and biologic effects of PIXY321 after chemotherapy in patients with ovarian carcinoma.


METHODS
A multicenter, nonrandomized, phase I/II study of subcutaneously administered PIXY321 after the second cycle of chemotherapy in cohorts of three or more patients at 50, 125, 250, 500, 750, or 100 micrograms/m2 per day.


RESULTS
Cyclophosphamide (600 mg/m2) and carboplatin (400 mg/m2) were administered every 28 days to 34 patients. At doses > or = 500 mg/m2 per day, the median nadir platelet and median nadir absolute neutrophil counts in cycle 2 (with PIXY321) compared with cycle 1 (control) were both higher in 13 of 26 (50%) patients. Twenty-one patients were withdrawn from the study. A total of 17 of 21 (81%) were removed for myelosuppression (n = 15) or PIXY321 toxicity (n = 2). A total of 28 of 34 (82%) patients had injection site reactions. Thirty-seven nonhematologic grade 3 events occurred.


CONCLUSIONS
At these doses and schedules PIXY321 can be safely administered. Aggressive dosing of cyclophosphamide and carboplatin could not be maintained for six cycles in the majority (62%) of patients.
Runowicz
C D
CD
Department of Obstetrics and Gynecology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Mandeli
J
J
Speyer
J L
JL
Wadler
S
S
Hochster
H
H
Garrison
L
L
Holland
J F
JF
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007377:Interleukin-3 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013921:Thrombocytopenia / Q000139:chemically induced
D007377:Interleukin-3; C078524:PIXY321 fusion protein, recombinant; D011993:Recombinant Fusion Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide; D016190:Carboplatin