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Aim: The aim of present study was to investigate the feasibility of a densified sequence of FEC75 (5-fluorouracil 600 mg/m2, epirubicin 75 mg/m2, cyclophosphamide 600 mg/m2) and docetaxel 100 mg/m2 (D100) in patients with primary operable high-risk breast cancer., Methods: Fifty-one consecutive patients with resectable breast cancer and 4 or more positive axillary lymph nodes were enrolled. After a common regimen of 4 cycles of FEC75 given every 14 days, patients received 4 cycles of D100 every 14 days. Prophylactic granulocyte colony-stimulating factor was administered subcutaneously at 5 mg/kg daily from days 5 to 10 to each patient., Results: The primary endpoint was the proportion of subjects receiving at least 85% of the relative dose intensity (rDI) both in the FEC and docetaxel parts of the regimen. In view of the high percentage of grade 3-4 skin toxicity (32%) observed in the first 25 patients (Group A) during D100 treatment, it was decided to continue the study using a docetaxel dose reduced by 15% (85 mg/m2; D85). This second group of 26 patients was defined as Group B. Of the total 51 patients, 38 (75%) received docetaxel rDI ≥85%, 23/26 patients (88.5%) and 15/25 patients (60.0%) in Group B and Group A, respectively. The observed grade 3-4 hematological and nonhematological toxicities were in line with data from the literature. The only significant difference was the higher percentage of grade 3-4 skin toxicity experienced with D100., Conclusion: This study failed to demonstrate the feasibility of a dose-dense FEC-D regimen with docetaxel 100 mg/m2. Docetaxel 85 mg/m2 seems to allow a higher rDI than docetaxel 100 mg/m2 but this should be confirmed in a larger cohort of patients.

The benefits of allografting noted in some malignant diseases might be safely extended to metastatic breast cancer by a combination of cytoreduction with high-dose chemotherapy (HDT) and autologous stem-cell transplant (ASCT) with graft-versus-tumour effect mediated by transplanted donor immune cells with nonmyeloablative allografting (reduced intensity conditioning transplantation, RICT). 17 patients with heavily pretreated disease were given tandem transplants. 13 patients sustained donor engraftment. Three had partial remission after HDT and ASCT and complete remission after RICT; they achieved full chimerism and all developed graft-versus-host disease (GVHD) before regression of cancer. Another patient did not respond to HDT and ASCT but had partial remission after RICT, giving an overall response rate of 24%. Five patients had grade II or higher acute GVHD and five had extensive chronic GVHD. No non-relapse-related deaths occurred during the first 100 days. Five patients (29%) were alive 90-2160 days (median 1320) after RICT. This two-step approach is feasible in patients with metastatic breast cancer.

We studied the safety, activity and peripheral blood progenitor cell mobilizing capability of a dose-dense combination of vinorelbine (VNB) and paclitaxel (PTX) as first-line chemotherapy for patients with metastatic breast cancer (MBC). Forty-three MBC patients were submitted to four cycles of VNB 30 mg/m2 and PTX 175 mg/m2 intravenously, every 2 weeks, as the first induction step of a tandem high-dose chemotherapy program. Granulocyte colony-stimulating factor (G-CSF) 5 microg/kg was administered daily from day +5 to +10 in order to accelerate hematopoietic recovery, or 48h after the last VNB-PTX when a leukapheresis was planned (after the third or fourth cycle). A total of 172 cycles were administered. The mean delivered dose-intensity of VNB and PTX was 14.7 and 86 mg/m2/week, respectively (98% of the planned dose-intensity). The main per-patient toxicities were: peripheral neurotoxicity (G1/2 60%, G3 5%), constipation (G1/2 10%), oral mucositis (G1/2 20%), and asthenia (G1/2 35%). Hematological toxicity was unremarkable, except for anemia with hemoglobin (Hb) values < 10 g/dl (28%), and lymphopenia with lymphocyte counts < 1000/mm3 (28%). Two complete (5.1%) and 24 partial (61.5%) responses were observed in 39 assessable patients, for an overall response rate of 66.6% (95% CI 51.6-80.9). A median of one apheretic procedure (range 1-3) was required to achieve the target number of 6 x 10(6)/kg CD34+ cells. The median number of CD34+ harvested per patient was 15 x 10(6)/kg (range 6.4-36.5). Four cycles of dose dense VNB and PTX showed a favorable toxicity profile, a relevant anti-tumor activity and a high peripheral blood progenitor cell mobilizing activity.

Background and Objectives: High-dose chemotherapy (HDT) with autologous peripheral blood progenitor cell (PBPC) transplant has been increasingly used for newly diagnosed multiple myeloma (MM) in recent years. Presently available results suggest an improvement in the complete remission rate and survival as compared to conventional chemotherapy. However, there is no plateau in the survival curves, and experiments with new treatment schedules and conditioning regimens are warranted., Design and Methods: In a non-randomised controlled trial, 20 patients underwent three-step HDT following conventional vincristine/doxorubicin/dexamethasone (VAD)-based induction. In the intensification phase patients received high-dose cyclophosphamide (HD-CY), high-dose etoposide (HD-VP), and mitoxantrone (NOV) plus melphalan (L-PAM) with haemopoietic rescue. Maintenance treatment with interferon was given until relapse. Actuarial overall survival (OS) and event-free survival (EFS) curves were plotted according to the method of Kaplan and Meier. In five of the eight patients achieving complete remission (CR), the molecular disease was monitored by polymerase chain reaction technique (PCR)., Results: Overall 18/20 (90%) patients responded, with a CR rate of 40%. After an average follow-up of 40 months, median EFS and OS are 25.5 and 44.6 months, respectively. Monoclonal cells were detectable in the post-treatment bone marrow and in the aphereses of the five CR patients monitored by PCR., Conclusion: The present three-step HDT regimen, including conditioning with mitoxantrone and melphalan, proved to be feasible and safe. Our results are in agreement with the hypothesis that HDT results in an increased remission rate and in prolonged survival in newly diagnosed MM, but a cure is unlikely.

The purpose of the present study was to evaluate the feasibility and the efficacy of employing a high-dose chemotherapy (HDT) regimen with tandem peripheral blood progenitor cells (PBPC) supported transplantation in the initial treatment of aggressive non-Hodgkin's lymphoma (NHL). HDT was preceded by a standard course of conventional dose chemotherapy in 17 out of the 25 patients treated, while in 8 cases it was delivered after only one or two cycles. HDT was a three-step procedure which included high-dose (6-7 g/m2) cyclophosphamide (CY) supported by haematopoietic growth factors, the first myeloablative course with mitoxantrone (NOV) 60, 75 or 90 mg/m2 plus melphalan (L-PAM) 140-180 mg/m2 with haematopoietic rescue, and the second myeloablative course with etoposide (VP) and carboplatin (CARBO) given at 1.5 g/m2 each with haematopoietic rescue. PBPC were collected after CY administration. Twenty-two patients (88%) completed the HDT, haematological reconstitution was rapid and complete at each step and there were no toxic deaths. The activity of the treatment was high with a CR rate over 90% in the entire patient population. The 2-year overall survival (OS) and failure-free survival (FFS) rates of patients in both Age-Adjusted International Prognostic Index (A-AIPI) groups 2 and 3 are 79% and the disease-free survival (DFS) rate for the CRs is 85%. In A-AIPI group 1 the 2-year OS and FFS rates are both 91%.

The aim of this study was to compare both the effects on hematologic recovery and circulating progenitor cell mobilization and the toxicity of three cytokine regimens administered after high-dose non-myeloablative chemotherapy with cyclophosphamide 5 g/m(2), etoposide 1.5 g/m(2) and cisplatin 150 mg/m(2). Thirty-five consecutive patients were non-random sequentially allocated to one of three treatment groups: (1) granulocyte colony-stimulating factor alone (n = 15); (2) granulocyte-macrophage colony-stimulating factor alone (n = 10), and (3) sequential interleukin-3 and granulocyte-macrophage colony-stimulating factor (n = 10). Neutrophil recovery in group 1 was significantly hastened as compared to the two other groups (median 2 days, p < 0.005), while no significant differences were observed between groups 2 and 3. CD34+ cells peaked about 2 days earlier in group 1 compared to the other groups (p = 0.0001), whereas the median peak value of CD34+ cells was similar in the three groups. In all patients, the toxicity related to cytokine administration was low and easily manageable with nonsteroidal anti-inflammatory drugs., (Copyright 2000 S. Karger AG, Basel)

Purpose: To compare the toxicity and effects on hematologic recovery and circulating progenitor cell mobilization of three cytokine regimens administered after high-dose cyclophosphamide (HD-CTX; 6 g/m(2)), given as the first step of a high-dose sequential chemotherapy., Patients and Methods: Forty-eight patients with breast cancer or non-Hodgkin's lymphoma were randomized to receive granulocyte colony-stimulating factor (G-CSF) alone (arm 1), granulocyte-macrophage colony-stimulating factor (GM-CSF) alone (arm 2), or sequential interleukin-3 (IL-3) and GM-CSF (arm 3). Cytokines were administered as a single daily subcutaneous injection at a dose of 5 to 6 microg/kg/d. Progenitor cells were evaluated in peripheral blood as well as in apheretic product as both CD34(+) cells and granulocyte-macrophage colony-forming units (CFU-GM)., Results: Neutrophil recovery was faster in arm 1 as compared with arms 2 and 3 (P <.0001); no significant differences were observed between arms 2 and 3. In arm 3, a moderate acceleration of platelet recovery was observed, but it was statistically significant only as compared with arm 1 (P =.028). The peak of CD34(+) cells was hastened in a median of 2 days in arm 1 compared with arms 2 and 3 (P =.0002), whereas the median peak value of CD34(+) cells and CFU-GM was similar in the three patient groups. Administration of IL-3 and GM-CSF resulted in more significant toxicity requiring pharmacologic treatment in 90% of patients., Conclusion: The three cytokine regimens administered after HD-CTX are comparably effective in reducing hematologic toxicity and mobilizing the hematopoietic progenitor cells. G-CSF accelerates leukocyte recovery and progenitor mobilization. Although G-CSF-treated patients have somewhat slower platelet recovery, they definitely have fewer side effects.