REPETITIVE CYCLES OF CYCLOPHOSPHAMIDE, THIOTEPA, AND CARBOPLATIN INTENSIFICATION WITH PERIPHERAL-BLOOD PROGENITOR CELLS AND FILGRASTIM IN ADVANCED BREAST-CANCER PATIENTS

Purpose: As an alternative to single-cycle cyclophosphamide, thiotepa, and carboplatin (CTCb) intensification, we evaluated the feasibility of administering one-quarter dose CTCb for four cycles with peripheral -blood progenitor-cell (PBPC) end filgrastim (granulocyte colony-stimu lating factor [G-CSF]) in advanced-stage breast cancer patients. Patie nts and Methods: From June 1992 to August 1993, 20 stage IIIB (n = 7) and IV (9 = 13) breast cancer patients received 78 cycles of induction with doxorubicin 90 mg/m(2) by intravenous (IV) bolus with G-CSF 5 mu g/kg/d by subcutaneous injection (SC) repeated every 14 to 21 days fo r four cycles. PBPC were collected by 2-hour single-blood volume leuka pheresis on 2 consecutive days at the time of hematologic recovery fro m each cycle of doxorubicin. Eighteen patients received 61 cycles of i ntensification with cyclophosphamide 1,500 mg/m(2), thiotepa 125 mg/m( 2), and carboplatin 200 mg/m(2) by IV continuous infusion with G-CSF 1 0 mu g/kg/d SC and PBPC support repeated every 21 to 42 days for four cycles. Results: Twelve of 20 patients (60%) completed all four planne d cycles of daxorubicin induction followed by four cycles of one-quart er dose CTCb intensification. Statistically significantly decreases in the yield of mononuclear cells (MNC) (median slope per day, -0.032; P = .03), granulocyte-macrophcIge colony-forming unit (CFU-GM) (median slope per day, -0.57; P = .0008), and burst-forming unit-erythroid (BF U-E) (median slope per day, -1.18; P = .006) were observed over the co urse of the eight leukaphereses. Of 18 patients who began CTCb, 12 (67 %) completed four cycles. Six patients were removed from study during intensification: two for progressive disease (PD), one refused further treatment, and three for dose-limiting hematologic toxicity. A fourth patient fulfilled the criteria for dose-limiting hematologic toxicity after cycle 4. The toxicity of the multiple cycle CTCb intensificatio n regimen consisted of grade IV leukopenia, grade IV thrombocytopenia, and febrile neutropenia in 100%, l00%, and 26% of cycles, respectivel y. The median duration of each CTCb cycle was 24 days (range, 18 to 63 ), and the median duration of an absolute neutrophil count (ANC) less than or equal to 500/mu L and platelet count less than or equal to 20, 000/mu L during each cycle was 6 days (range, 2 to 15) and 4 days (ran ge, 0 to 38), respectively. Conclusion: It is feasible to administer r epetitive cycles of one-quarter dose CTCb intensification with PBPC an d G-CSF. Additional studies are required to determine whether multiple cycles of CTCb intensification might offer a therapeutic advantage ov er a single high-dose cycle. (C) 1997 by American Society of Clinical Oncology.