High-dose carboplatin, thiotepa and cyclophosphamide (CTC) with peripheral blood stem cell support in the adjuvant therapy of high-risk breast cancer: a practical approach

Abstract

Summary In 29 chemotherapy-naive patients with stage II-III breast cancer, peripheral blood stem cells (PBSCs) were mobilised following fluorouracil 500mg m-2, epirubicin 90-120mg m2 and cyclophosphamide 500 mg m-2 (FEC) and granulocyte colony-stimulating factor (G-CSF; Filgrastim) 300 iLg s.c. daily. In all but one patient, mobilisation was successful, requiring three or fewer leucocytopheresis sessions in 26 patients; 28 patients subsequently underwent high-dose chemotherapy consisting of carboplatin 1600 mg m-2, thiotepa 480 mg m-2 and cyclophosphamide 6 g m-2 (CTC) followed by PBSC transplantation. Haemopoietic engraftment was rapid with a median time to neutrophils of 500 x 10 1-' of 9 days (range 8-10) in patients who received G-CSF after PBSC-transplantation; platelet transfusion independence was reached within a median of 10 days (range 7-16). Neutropenic fever occurred in 96% of patients. Gastrointestinal The ability of adjuvant chemotherapy to improve long-term disease-free and overall survival in patients with breast cancer and tumour-positive axillary lymph nodes is now widely recognised (Early Breast Cancer Trialists' Collaborative Group, 1992;Olivotto et al., 1994). The precise characteristics of patient groups that benefit most from this treatment modality and the optimal type, duration and intensity of chemotherapy, however, continue to be the subjects of intensive research (Fisher et al., 1992).One major approach to further improve the results of chemotherapy in breast cancer is dose intensification (Antman, 1992a;Wood et al., 1994). Studies with haematological growth factors such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have shown that the chemotherapy dose per unit of time can be increased by a factor 1.5-2.0 (as compared with 'standard' doses) in young patients with breast cancer (Bronchud et al., 1989;Gianni et al., 1990). At these dose levels, thrombocytopenia and organ toxicity become dose-limiting. In non-randomised studies, this type of intensified chemotherapy typically leads to high response rates in patients with advanced disease, but not to long-term survival. Further dose escalation, beyond the levels achievable with growth factors alone, requires autologous bone marrow stem cell support. In patients with advanced disease, high-dose multiple alkylator chemotherapy may lead to a 17-26% long-term disease-free survival (Livingston, 1994). Subgroup analyses of non-randomised studies suggest that patients who receive high-dose chemotherapy as consolidation treatment in a chemotherapy-induced complete remission may profit most (Klumpp et al., 1994 (Gianni et al., 1992;Mulder et al., 1993; Peters et al., 1993). The largest of these (Peters et al., 1993) reported on 85 patients, who received four cycles of cyclophosphamide, doxorubicin and fluorouracil, followed by a high-dose chemotherapy regimen incorporating cyclophosphamide, cisplatin and BCNU. The relapse-free survival of these patients appears to be markedly im...

High-dose chemotherapy supported by peripheral blood progenitor cells in poor prognosis metastatic breast cancer--phase I/II study

“…They have been used in other series because of overt bone marrow involvement, with the reported haematopoietic recovery and patient survival times being similar to those seen here (Somlo et al, 1994;Myers et al, 1994;Hester and Wallerstein, 1993;Kritz et al, 1993). In contrast, the more prolonged recovery for patients receiving ABMT is well recognised; and although we did not employ G-CSF after PBPC, this can further hasten neutrophil recovery (van der Wall et al, 1995) (Antman, 1992). Having established the safety of melphalan and etoposide with PBPC support in pretreated metastatic breast cancer, we then administered thiotepa in place of the etoposide, intending to dose escalate both the thiotepa and melphalan.…”

Toxicity of the high-dose chemotherapy CTC regimen (cyclophosphamide, thiotepa, carboplatin): the Netherlands Cancer Institute experience

“…The procedures of bone marrow harvesting and leucoytaphoris have been described previously (van der Wall et al, 1995;Rodenhuis et al, 1996Rodenhuis et al, , 1998Rodenhuis et al, , 1999Rodenhuis et al, , 2000.…”

“…The peripheral blood progenitor cell reinfusion (PBPC-Tx) was performed 2 days after the end of the chemotherapy. The prophylactic use of antiemetics and antibiotics of the separate studies have been described elsewhere (Rodenhuis et al, 1992(Rodenhuis et al, , 1996van der Wall et al, 1995). Briefly, all patients received antiemetics prophylactically, consisting of dexamethasone and serotonin antagonist and/or metoclopramide.…”

“…It contains the same agents as STAMP-V, but the carboplatin dose is twice as high and the agents are administered as short-term infusions rather than as continuous infusions. CTC has been used in several randomised and nonrandomised studies in high-risk (van der Wall et al, 1995;Rodenhuis et al, 1996Rodenhuis et al, , 1998Rodenhuis et al, , 1999Rodenhuis et al, , 2000Schrama et al, 2002) and in stage IV breast cancer (Schrama et al, 2001;De Gast et al, 2002) and, moreover, in the salvage therapy of germ cell cancer (Rodenhuis et al, 1996.…”

Hematological recovery and peripheral blood progenitor cell mobilization after induction chemotherapy and GM-CSF plus G-CSF in breast cancer

“…Indeed, our results were two-to three-fold greater than those obtained with different mobilization regimens in breast cancer. 20,[27][28][29][30] …”