First-line high-dose sequential chemotherapy with rG-CSF and repeated blood stem cell transplantation in untreated inflammatory breast cancer: toxicity and response (PEGASE 02 trial)

Abstract

Despite the generalization of induction chemotherapy and a better outcome for chemosensitive diseases, the prognosis of inflammatory breast cancer (IBC) is still poor. In this work, we evaluate response and toxicity of high-dose sequential chemotherapy with repeated blood stem cell (BSC) transplantation administered as initial treatment in 100 women with non-metastatic IBC. Ninety-five patients (five patients were evaluated as non-eligible) of median age 46 years (range 26–56) received four cycles of chemotherapy associating: cyclophosphamide (C) 6 g m −2 – doxorubicin (D) 75 mg m −2 cycle 1, C: 3 g m −2 – D: 75 mg m −2 cycle 2, C: 3 g m −2 – D: 75 mg m −2 – 5 FU 2500 mg m −2 cycle 3 and 4. BSC were collected after cycle 1 or 2 and reinfused after cycle 3 and 4. rG-CSF was administered after the four cycles. Mastectomy and radiotherapy were planned after chemotherapy completion. Pathological response was considered as the first end point of this trial. A total of 366 cycles of chemotherapy were administered. Eighty-seven patients completed the four cycles and relative dose intensity was respectively 0.97 (range 0.4–1.04) and 0.96 (range 0.25–1.05) for C and D. Main toxicity was haematological with febrile neutropenia ranging from 26% to 51% of cycles; one death occurred during aplasia. Clinical response rate was 90% ± 6%. Eighty-six patients underwent mastectomy in a median of 3.5 months (range 3–9) after the first cycle of chemotherapy; pathological complete response rate in breast was 32% ± 10%. All patients were eligible to receive additional radiotherapy. High-dose chemotherapy with repeated BSC transplantation is feasible with acceptable toxicity in IBC. Pathological response rate is encouraging but has to be confirmed by final outcome. © 1999 Cancer Research Campaign

Multivariate analysis of survival in inflammatory breast cancer: impact of intensity of chemotherapy in multimodality treatment

“…However, inclusion criteria and staging evaluation were similar for all women and our two so-defined groups of patients were 23,28,29,[36][37][38][39] or as first-line therapy. 10 Globally, even if it is difficult to compare these studies, which are often multicentre and/or with small heterogeneous cohorts in terms of treatment and follow-up, the 3-or 4-year DFS rates (from 45 to 65%) and OS rates (from 52 to 89%) are similar to each other and comparable to our series. To date, no randomised clinical trial has compared HDC with HSCS and conventional chemotherapy in IBC, probably because of the rarity of disease and the absence of real consensus chemotherapy.…”

“…These rates are comparable with those published for conventional or semi-intensive chemotherapy (from 0 to 25%) 4,8,[24][25][26][27] and for HDC with HSCS (from 14 to 39%). 10,23,28,29 As pathological response has been reported as a prognostic factor, 4,5,[24][25][26]30,31 the identification of predictive factors is warranted. To date, no single clinicopathological parameter has been proved reliably predictive in IBC and very few data are available about molecular features.…”

“…Some of these patients have been previously reported. 10,23 Mastectomy following chemotherapy was performed in most cases and allowed evaluation of the pathological response to chemotherapy. Pathological complete response was observed in 26% of all patients, in 17% of those treated with conventional doses and in 27% of those treated with HDC Table 2 Pathological response to primary chemotherapy and clinical outcome (n ¼ 74)…”

“…It consisted of four cycles of a dose-intensified regimen combining the same drugs as those used at conventional doses, with collection of peripheral blood stem cells after cycles 1 and 2, and reinfusion after cycles 3 and 4 (cyclophosphamide 6 g/ m 2 and doxorubicin 75 mg/m 2 cycle 1; cyclophosphamide 3 g/m 2 and doxorubicin 75 mg/m 2 cycle 2; cyclophosphamide 3 g/m 2 , doxorubicin 75 mg/m 2 and fluorouracil 2.500 mg/m 2 cycles 3 and 4). 10 No purging of graft was performed. After completion of chemotherapy 62 patients underwent mastectomy, with axillary dissection (25 cases) if not performed at diagnosis.…”

A phase I/II study of 4 monthly courses of high-dose cyclophosphamide and thiotepa for metastatic breast cancer patients

“…The association of G-CSF and PBPC supports allows rapid haematological recovery after each cycle, making haematological toxicities easily manageable on an outpatient basis (Basser et al, 1995;Rodenhuis et al, 1996;Viens et al, 1999). Interestingly, haematological toxicity as evaluated by the duration of neutropenia, thrombopenia, incidence of transfusion and delay to haematopoietic reconstitution did not significantly increase between courses one and four for all patients in this study.…”