Mobilization protocols of peripheral blood progenitor cells (PBPCs) include the administration of growth factors alone or during the recovery from chemotherapy. Protocols that mobilize increased numbers of PBPCs are being investigated. Amifostine (AMI), a phosphorylated aminothiol, increases the selectivity of anticancer drugs for neoplastic cells, protects normal tissues from radio-chemotherapy toxicities and stimulates in vivo hematoppiesis. The aim of the present study was to investigate the role of AMI in conjunction with Epirubicin (EPI) and G-CSF to enhance PBPC mobilization. Ten patients with advanced solid tumors who were administered with two cycles of EPI (120 mg/sqm on day 0) plus G-CSF (5 |lg/kg/d, days 1-10) at 3-week interval were randomized to receive AMI on first or second cycle. AMI was administered i.v. for 5 days (day 0: 1,000 mg, days 1-4: 500 mg/d). Once daily, from day 0 to 10, white blood cell (WBC) and platelet (Pit) counts, CD34 cells, and progenitor cell incidence (CPU-Mix, BFU-E, CFU-GM, LTC-IC) were evaluated. Currently, eight patients (2 untreated and 6 pre-treated with 7 to 17 chemotherapy cycles) who received AMI at the first (n = 4) or second (n = 4) cycle are évaluable. WBC and Pit counts were not affected by AMI administration. In contrast, EPI+G-CSF+AMI compared to EPI+G-CSF induced a statistically significant (P<.05) increase of day 10 incidence (meaniSEM) of CD34 cells/nl (112±18 vs 71±21), CFUMix/ml (554±235vs 128±38), BFU-E/ml (6,684±1,792 vs 1,913±174) and CFU-GM/ml (12,808±3,899 vs 4,526±1,204). As compared to day 0 values, EPI+G-CSF+AMI versus EPI+G-CSF resulted in significantly higher fold increases for CPU-Mix (81 vs 7), BFU-E (73 vs 41), and CFU-GM (195 vs 105). Addition of AMI to EPI-K3-CSF induced a potentiation of LTC-IC, CPU-Mix, BFU-E and CFU-GM growth by 3, 13, 10, and 14-fold, respectively. AMI-induced enhancement of PBPC mobilization was evident in patients receiving AMI both at the first or second cycle of chemotherapy. This ongoing randomized study demonstrates that addition of AMI to EPI+G-CSF significantly increases the mobilization of CD34 cells, primitive and committed progenitors in pretreated solid tumor patients.
Peripheral blood progenitor cell mobilization is significantly enhanced by amifostine
Carlo Stella C.;
1998-01-01
Abstract
Mobilization protocols of peripheral blood progenitor cells (PBPCs) include the administration of growth factors alone or during the recovery from chemotherapy. Protocols that mobilize increased numbers of PBPCs are being investigated. Amifostine (AMI), a phosphorylated aminothiol, increases the selectivity of anticancer drugs for neoplastic cells, protects normal tissues from radio-chemotherapy toxicities and stimulates in vivo hematoppiesis. The aim of the present study was to investigate the role of AMI in conjunction with Epirubicin (EPI) and G-CSF to enhance PBPC mobilization. Ten patients with advanced solid tumors who were administered with two cycles of EPI (120 mg/sqm on day 0) plus G-CSF (5 |lg/kg/d, days 1-10) at 3-week interval were randomized to receive AMI on first or second cycle. AMI was administered i.v. for 5 days (day 0: 1,000 mg, days 1-4: 500 mg/d). Once daily, from day 0 to 10, white blood cell (WBC) and platelet (Pit) counts, CD34 cells, and progenitor cell incidence (CPU-Mix, BFU-E, CFU-GM, LTC-IC) were evaluated. Currently, eight patients (2 untreated and 6 pre-treated with 7 to 17 chemotherapy cycles) who received AMI at the first (n = 4) or second (n = 4) cycle are évaluable. WBC and Pit counts were not affected by AMI administration. In contrast, EPI+G-CSF+AMI compared to EPI+G-CSF induced a statistically significant (P<.05) increase of day 10 incidence (meaniSEM) of CD34 cells/nl (112±18 vs 71±21), CFUMix/ml (554±235vs 128±38), BFU-E/ml (6,684±1,792 vs 1,913±174) and CFU-GM/ml (12,808±3,899 vs 4,526±1,204). As compared to day 0 values, EPI+G-CSF+AMI versus EPI+G-CSF resulted in significantly higher fold increases for CPU-Mix (81 vs 7), BFU-E (73 vs 41), and CFU-GM (195 vs 105). Addition of AMI to EPI-K3-CSF induced a potentiation of LTC-IC, CPU-Mix, BFU-E and CFU-GM growth by 3, 13, 10, and 14-fold, respectively. AMI-induced enhancement of PBPC mobilization was evident in patients receiving AMI both at the first or second cycle of chemotherapy. This ongoing randomized study demonstrates that addition of AMI to EPI+G-CSF significantly increases the mobilization of CD34 cells, primitive and committed progenitors in pretreated solid tumor patients.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
