TY - JOUR
T1 - Effects of PIXY321, a granulocyte-macrophage colony-stimulating factor/interleukin-3 fusion protein, on chemotherapy-induced multilineage myelosuppression in patients with sarcoma
AU - Vadhan, Saroj
AU - Papadopoulos, Nicholas E.
AU - Burgess, Michael A.
AU - Linke, Kaye A.
AU - Patel, Shreyaskumar R.
AU - Hays, Carolyn
AU - Arcenas, Anthony
AU - Plager, Carl
AU - Kudelka, Andrzej P.
AU - Hittelman, Walter N
AU - Broxmeyer, Hal E.
AU - Williams, Douglas E.
AU - Garrison, Leslie
AU - Benjamin, Robert S
PY - 1994/4
Y1 - 1994/4
N2 - Purpose: To evaluate the clinical safety and ability of PIXY321, a novel fusion protein of recombinant human granulocyte-macrophage colony- stimulating factor (GM-CSF) and interleukin-3 (IL-3), to ameliorate chemotherapy-induced multilineage myelosuppression. Patients and Methods: PIXY321 was administered by subcutaneous injection twice daily (25 to 1,000 μg/m2/d) over 14 days to 24 chemotherapy-naive patients with sarcoma in a phase I/II study. Three weeks from the initiation of PIXY321, the first cycle of chemotherapy with cyclophosphamide, doxorubicin, and dacarbazine (DTIC) (CyADIC) was administered over 3 days. Four weeks later, a second cycle of CyADIC was administered, followed by 14 days of PIXY321. Results: Treatment with PIXY321 was well tolerated. Local skin reactions and constitutional symptoms were the main side effects. The dose-limiting toxicity was not encountered; however, headache and fatigue were more frequent at the highest dose (1,000 μg/m2). PIXY321 before chemotherapy elicited a modest increase in the WBC count (consisting mainly of mature neutrophils), platelets, and corrected reticulocyte counts (all P < .001). Following chemotherapy, PIXY321 at effective doses (500 to 1,000 μg/m2/d), significantly reduced both the degree (mean nadir, 70 v 310/μL; P = .016) and duration (mean days < 500/μL, 6.6 v 3.9 days; P = .002) of neutropenia. Cumulative thrombocytopenia was not observed during the first two cycles of CyADIC (mean nadir platelet count, 103 v 95 x 103/μL, in cycles no. 1 and 2, respectively; P = NS). Compared with our historic control data, the mean nadir platelet count in cycle no. 2 was significantly higher after PIXY321 (1.7-fold, P < .05) than with CyADIC alone or with GM-CSF support. There was a suggestion for a dose response, since the mean percentage change in nadir platelet values from cycle no. 1 to cycle no. 2 increased with the PIXY321 dose (P < .02), with the peak effect observed at 750 μg/m2/d. Conclusion: These results suggest a potential clinical role for PIXY321 in attenuating the cumulative multilineage hematopoietic toxicity of chemotherapy.
AB - Purpose: To evaluate the clinical safety and ability of PIXY321, a novel fusion protein of recombinant human granulocyte-macrophage colony- stimulating factor (GM-CSF) and interleukin-3 (IL-3), to ameliorate chemotherapy-induced multilineage myelosuppression. Patients and Methods: PIXY321 was administered by subcutaneous injection twice daily (25 to 1,000 μg/m2/d) over 14 days to 24 chemotherapy-naive patients with sarcoma in a phase I/II study. Three weeks from the initiation of PIXY321, the first cycle of chemotherapy with cyclophosphamide, doxorubicin, and dacarbazine (DTIC) (CyADIC) was administered over 3 days. Four weeks later, a second cycle of CyADIC was administered, followed by 14 days of PIXY321. Results: Treatment with PIXY321 was well tolerated. Local skin reactions and constitutional symptoms were the main side effects. The dose-limiting toxicity was not encountered; however, headache and fatigue were more frequent at the highest dose (1,000 μg/m2). PIXY321 before chemotherapy elicited a modest increase in the WBC count (consisting mainly of mature neutrophils), platelets, and corrected reticulocyte counts (all P < .001). Following chemotherapy, PIXY321 at effective doses (500 to 1,000 μg/m2/d), significantly reduced both the degree (mean nadir, 70 v 310/μL; P = .016) and duration (mean days < 500/μL, 6.6 v 3.9 days; P = .002) of neutropenia. Cumulative thrombocytopenia was not observed during the first two cycles of CyADIC (mean nadir platelet count, 103 v 95 x 103/μL, in cycles no. 1 and 2, respectively; P = NS). Compared with our historic control data, the mean nadir platelet count in cycle no. 2 was significantly higher after PIXY321 (1.7-fold, P < .05) than with CyADIC alone or with GM-CSF support. There was a suggestion for a dose response, since the mean percentage change in nadir platelet values from cycle no. 1 to cycle no. 2 increased with the PIXY321 dose (P < .02), with the peak effect observed at 750 μg/m2/d. Conclusion: These results suggest a potential clinical role for PIXY321 in attenuating the cumulative multilineage hematopoietic toxicity of chemotherapy.
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U2 - 10.1200/JCO.1994.12.4.715
DO - 10.1200/JCO.1994.12.4.715
M3 - Article
C2 - 8151315
AN - SCOPUS:0028255994
SN - 0732-183X
VL - 12
SP - 715
EP - 724
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 4
ER -