Ifosfamide in combination with paclitaxel or doxorubicin: regimens which effectively mobilize peripheral blood progenitor cells while demonstrating anti-tumor activity in patients with metastatic breast cancer

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Summary:We prospectively evaluated docetaxel (100 mg/m 2 ) with G-CSF (10 g/kg S.C., daily) for mobilization efficiency in 26 patients with breast cancer. The minimum target yield was Ͼ4.5 ؋ 10 6 CD34 ؉ cells/kg (optimum = 9 ؋ 10 6 /kg), sufficient to support the subsequent three cycles of high-dose therapy (HDT). The peak days for peripheral blood (PB) CD34؉ cells were day 8 and day 9. Seven collections began on day 7, 16 on day 8 and three on day 9. The median peripheral blood progenitor cell (

Section: Discussionmentioning

confidence: 99%

Docetaxel effectively mobilizes peripheral blood CD34+ cells

Prince

Toner

Seymour

et al. 2000

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“…[2][3][4][5][6][7] The other available taxane, paclitaxel, has been shown to be an effective PBPC mobilizer as a single agent and in combination with cyclophosphamide and etoposide, epirubicin, ifosfamide and high-dose cyclophosphamide. [8][9][10][11][12][13][14][15] As single agents, both docetaxel and paclitaxel induce WBC nadirs of brief duration without severe thrombocytopenia. Docetaxel can be safely administered on an outpatient basis as it causes minimal nausea and vomiting and does not require aggressive intravenous hydration as do the more traditional chemotherapeutic mobilizing regimens involving high-dose cyclophosphamide.…”

mentioning

confidence: 99%

A phase II trial of docetaxel for peripheral blood stem cell mobilization for patients with breast cancer and ovarian cancer

Fleming

Waggoner

Zimmerman

et al. 2001

Summary:As docetaxel is known to have significant antineoplastic activity against breast and ovarian cancer, we explored its application as a peripheral blood stem cell mobilizing agent in 33 women with stage lll-IV ovarian carcinoma (n ‫؍‬ 10) or stage ll-lV breast cancer (n ‫؍‬ 23) who were in preparation for high-dose chemotherapy. Eleven patients had bone and/or bone marrow involvement with their disease. The median number of prior regimens received before mobilization was two (range 1-3). The three dose levels administered were 100 mg/m 2 , 110 mg/m 2 and 120 mg/m 2 . Patients received one dose of docetaxel in the outpatient setting followed by G-CSF (10 g/kg/day) starting 4 days after docetaxel administration. Leukapheresis commenced when WBC Ͼ1.0 ؋ 10 9 /l or when the WBC began to rise after reaching a nadir. Ninety-seven percent of patients began leukapheresis within 7-9 days after receiving docetaxel (range 7-10 days). The collection goal was у2 ؋ 10 6 CD34 ؉ cells/kg. Twenty-seven (82%) patients reached this goal in a median of 2 leukapheresis days (range 1-3). No grade 2-4 nonhematologic toxicities were noted. Thirteen patients (55%) showed a WBC nadir Ͼ1.0 ؋ 10 9 /l. None of the patients experienced neutropenic fever or required blood or platelet transfusion support. In conclusion, docetaxel ؉ G-CSF is an effective, well-tolerated regimen for PBPC mobilization which can be safely administered in the outpatient setting with minimal toxicity. Bone Marrow Transplantation (2001) 27, 677-681. Keywords: docetaxel; taxane; stem cells; mobilization Peripheral blood progenitor cells (PBPC) were initially harvested without prior stimulation but it is known that circulating progenitors markedly increase during the recovery phase after myelosuppressive chemotherapy. The recovery of bone marrow after chemotherapy-induced myelosuppression typically produces an abundant release of progenitor cells into the peripheral blood and the magnitude of the increase in circulating progenitor cells appears to correlate

“…19 Ifosfamide has been used in different PBPC mobilization methods at doses ranging from 4 to 6 g/m 2 but always in combination with other chemotherapy agents and administered for 3-5 days. 14,15 In the present study, our data shows that IFO+GM-CSF and CY+GM-CSF are both effective regimens for PBPC mobilization, even in heavily pretreated patients (most of the patients had received more than 10 cycles of chemotherapy before mobilization). During the mobilization phase our patients treated with IFO+GM-CSF had: (1) earlier mobilization, (2) fewer days treated with GM-CSF, (3) fewer days of aplasia and consequently fewer days with fever and antibiotics.…”

Section: Discussionmentioning

confidence: 81%

Prospective randomized clinical trial comparing high-dose ifosfamide + GM-CSF vs high-dose cyclophosphamide + GM-CSF for blood progenitor cell mobilization

Vela‐Ojeda

Tripp-Villanueva

Montiel‐Cervantes

et al. 2000

Summary:Between August 1994 and June 1999, 56 patients were prospectively randomized to receive ifosfamide 10 g/m 2 + GM-CSF 5 g/kg/day (IFO+GM-CSF n = 28) and cyclophosphamide 4 g/m 2 + GM-CSF 5 g/kg/day (CY+GM-CSF n = 28). Both groups were comparable for age, gender, diagnosis, disease stage and previous chemotherapy. The IFO+GM-CSF group demonstrated a shorter median interval between therapy and apheresis (10 days (8-14) vs 13 days (8-25) P = 0.002), median number of doses of GM-CSF (9 (7-13) vs 15 (9-31) P = 0.001), median of days with aplasia (0.5 (0-10) vs 6 (0-21) P = 0.001), median days with fever (0 (0-6) vs 3 (0-9) P = 0.006) and median of days using i.v. antibiotics (0 (0-11) vs 7.5 (0-19) P = 0.002). The median MNC yield was similar in both groups. The CD34 + cell yield was better in the CY+GM-CSF group (3.14 (0.9-11.8) vs 5.33 (0.08-32)) but not at significant levels (P = 0.1). White blood cell hematopoietic recovery was more rapid in the CY+GM-CSF group (16 (10-22) vs 13 (10-24) P = 0.02). Platelet engraftment was similar in both groups. Costs of mobilization and transplantation were almost the same: $28 570 ($18 527-$47 028) and $30 020 ($17 281-$67 591), respectively (P = 0.9). There were no differences in disease-free survival and overall survival between both groups. Mild and transient non-hematological toxicity (hemorrhagic cystitis, decrease in serum creatinine clearance and CNS dysfunction) was seen most frequently in the IFO+GM-CSF group. Bone Marrow Transplantation (2000) 25, 1141-1146.