High-dose carboplatin, etoposide and melphalan (CEM) with peripheral blood progenitor cell support as late intensification for high-risk cancer: non-haematological, haematological toxicities and role of growth factor administration

Abstract

Summary The present report describes the non-haematological toxicity and the influence of growth factor administration on haematological toxicity and haematopoietic recovery observed after high-dose carboplatin (1200 mg m-2), etoposide (900 mg m-2) and melphalan (100 mg m-2) (CEM) followed by peripheral blood progenitor cell transplantation (PBPCT) in 40 patients with high-risk cancer during their first-line treatment. PBPCs were collected during the previous outpatient induction chemotherapy programme by leukaphereses. CEM administration with PBPCT was associated with low non-haematological toxicity and the only significant toxicity consisted of a reversible grade III/IV increase in liver enzymes in 32% of the patients. Haematopoietic recovery was very fast in all patients and the administration of granulocyte colony-stimulating factor (G-CSF) plus erythropoietin (EPO) or granulocyte-macrophage colony-stimulating factor (GM-CSF) plus EPO after PBPCT significantly reduced haematological toxicity, abrogated antibiotic administration during neutropenia and significantly reduced hospital stay and patient's hospital charge compared with patients treated with PBPCT only. None of the patients died early of CEM plus PBPCTrelated complications. Low non-haematological toxicity and accelerated haematopoietic recovery renders CEM with PBPC/growth factor support an acceptable therapeutic approach in an adjuvant or neoadjuvant setting.

Optimization of recombinant human erythropoietin therapy after allogeneic hematopoietic stem cell transplantation

“…transfusion requirements after autologous HSCT [16][17][18][19][20][21][22]. In contrast, clinical trials of rhEpo therapy after allogeneic bone marrow transplantation (BMT) resulted in accelerated erythroid engraftment and some reduction in transfusion requirements [17,18,[23][24][25][26][27][28][29][30].…”

High-dose chemotherapy as a consolidation approach in advanced ovarian cancer: long-term results

“…Moreover, the percentage of therapy-related deaths was in keeping with the results reported in the literature. 3,8,10 The clinical benefits produced by the use of hematopo-ietic growth factors after HDC and PBSC reinfusion are well established 13,28 even though the ideal combinations of growth factors have yet to be defined. We reported previously the advantage of adding rh-EPO to myelopoietic growth factors which translates into a potentiation of their effects in vitro and in vivo.…”

“…As previously described, 12,13 eligibility criteria for HDC were the presence of histologically confirmed, advanced (FIGO stage IIIB-IV) epithelial ovarian cancer with a residual tumor р2 cm achieved at primary cytoreductive surgery or interval debulking surgery (IDS), no signs of progression after induction chemotherapy, age younger than 60 years, performance status of 0-1 (WHO scale), adequate bone marrow reserve (WBC count Ͼ4000 ϫ 10 6 /l, platelet count Ͼ100 ϫ 10 9 /l) and adequate pulmonary, cardiac, hepatic and renal function, as previously described. 12,13 The study was approved by the Hospital Human Investigation Review Board of the Catholic University and all patients gave informed consent.…”

“…12,13 The study was approved by the Hospital Human Investigation Review Board of the Catholic University and all patients gave informed consent.…”

“…1,[7][8][9][10][11][12] Our previous report on HDC in ovarian cancer showed encouraging results in terms of prolongation of time to progression and overall survival 12 and acceleration of hematopoietic recovery due to the combined administration of PBSC and growth factors. 13 Here, we report the updated results of the use of HDC 12 in a larger series of patients. The long-term impact of HDC has been investigated in patients selected on the basis of pathological characteristics and the presence of chemosensitive disease.…”