A PHASE-I STUDY OF SEQUENTIAL VERSUS CONCURRENT INTERLEUKIN-3 AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN ADVANCED BREAST-CANCER PATIENTS TREATED WITH FLAC (5-FLUOROURACIL, LEUCOVORIN, DOXORUBICIN,CYCLOPHOSPHAMIDE) CHEMOTHERAPY

Citation
Ja. Oshaughnessy et al., A PHASE-I STUDY OF SEQUENTIAL VERSUS CONCURRENT INTERLEUKIN-3 AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN ADVANCED BREAST-CANCER PATIENTS TREATED WITH FLAC (5-FLUOROURACIL, LEUCOVORIN, DOXORUBICIN,CYCLOPHOSPHAMIDE) CHEMOTHERAPY, Blood, 86(8), 1995, pp. 2913-2921
Citations number
45
Categorie Soggetti
Hematology
Journal title
BloodACNP
ISSN journal
00064971
Volume
86
Issue
8
Year of publication
1995
Pages
2913 - 2921
Database
ISI
SICI code
0006-4971(1995)86:8<2913:APSOSV>2.0.ZU;2-2
Abstract
Cumulative thrombocytopenia is a dose-limiting toxicity of dose-intens ive chemotherapy for advanced breast cancer. In this phase I study, we have studied the hematologic toxicity associated with sequential inte rleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF; molgramostim) administration after multiple cycles of FLAC (5 -fluorouracil, leucovorin, doxorubicin, cyclophosphamide) chemotherapy compared with that after concurrent cytokine administration or to eac h cytokine administered alone. Ninety-three patients with advanced bre ast cancer were treated with five cycles of FLAC chemotherapy and eith er IL-3 alone, GM-CSF alone, sequential IL-3 and GM-CSF administered b y schedule A (5 days of IL-3 followed by 10 days of GM-CSF) or schedul e B (9 days of IL-3 followed by 6 days of GM-CSF), or concurrent admin istration of IL-3 and GMCSF for 15 days. Cohorts of patients were trea ted with one of four dose levels of IL-3 (1, 2.5, 5, and 10 mu g/kg) a dministered subcutaneously for each schedule of cytokine administratio n. The GM-CSF dose in all schedules was 5 mu g/kg/day. Sequential IL-3 and GM-CSF (schedule B) was associated with higher platelet nadirs, s horter durations of platelet counts less than 50,000/mu L, and the nee d for fewer platelet transfusions over five cycles of FLAC chemotherap y compared with concurrent cytokines, sequential IL-3 and GM-CSF sched ule A, and GM-CSF alone. Concurrent IL-3 and GM-CSF was associated wit h unexpected platelet toxicity. The duration of granulocytopenia after FLAC chemotherapy was significantly worse with IL-3 alone compared wi th each of the GM-CSF-containing cytokine regimens. Although no cycle 1 maximum tolerated dose for IL-3 was defined in this study, 5 mu g/kg was well tolerated over multiple cycles of therapy and is recommended for future studies. The data from this phase I study suggest that seq uential IL-3 and GMCSF with IL-3 administered for 9 days before beginn ing GM-CSF may be superior to shorter durations of IL-3 administered s equentially with GM-CSF, to concurrent IL-3 and GM-CSF, and to either colony-stimulating factor alone in ameliorating the cumulative hematol ogic toxicity associated with multiple cycles of FLAC chemotherapy. Ad ditional studies of sequential IL-3 and GM-CSF are warranted. This is a US government work. There are no restrictions on its use.