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PubMed2004

Pegfilgrastim use during chemotherapy: current and future applications.

Chemotherapy-induced myelosuppression is the most common dose-limiting side effect of cancer chemotherapy. Neutropenia is a serious risk with chemotherapy, associated with infectious complications, use of intravenous antibiotics, hospitalization, and even death. The occurrence of febrile neutropenia can lead to dose reductions and delay in subsequent cycles of chemotherapy that may have a detrimental affect on overall survival and disease-free survival. Granulocyte colony-stimulating factors (G-CSF) can reduce the duration of severe neutropenia, the incidence of febrile neutropenia, and allow planned dosing and timing of chemotherapy. Filgrastim is a G-CSF that has demonstrated benefit for the treatment and prophylaxis of chemotherapy-induced neutropenia (CIN), but its short half-life requires repeated daily subcutaneous injection. Pegfilgrastim is a recombinant G-CSF created by attaching a polyethylene glycol (PEG) molecule to the filgrastim protein. Once-per-cycle dosing of pegfilgrastim has been evaluated in clinical trials using myelosuppressive chemotherapy in breast cancer, Hodgkin's lymphoma, and non-Hodgkin's lymphoma. Trials have demonstrated that pegfilgrastim is comparable in safety and efficacy to filgrastim for decreasing the duration of severe neutropenia after chemotherapy in patients with nonmyeloid malignancy. This review will summarize recent clinical trial results and novel uses of pegfilgrastim.

Antineoplastic Agents↗
PubMed2005

Single-dose pegfilgrastim for the mobilization of allogeneic CD34+ peripheral blood progenitor cells in healthy family and unrelated donors.

BACKGROUND AND OBJECTIVES: Short-term treatment with granulocyte colony-stimulating factor (G-CSF) has been established as the standard regimen for mobilizing allogeneic peripheral blood progenitor cells (PBPC) from healthy donors. The pegylated form of filgrastim (pegfilgrastim) has a longer elimination half-life because of decreased serum clearance and might be a convenient alternative for stem cell mobilization. DESIGN AND METHODS: Twenty-five family (n=15) or unrelated (n=10) healthy donors received a single-dose of 12 mg pegfilgrastim for mobilization of allogeneic PBPC. Donors with inadequate mobilization (blood CD34+ cells <or=5/microL on day 3 or <or=20/mL on day 4) were given additional daily doses of 10 mg/kg conventional filgrastim. Leukapheresis was planned to start on day 5. RESULTS: All harvests were completed successfully. In 20 out of 25 donors (80 %) only a single apheresis was necessary. Additional non-pegylated filgrastim had to be given to only one 74-year old family donor. The maximum concentration of circulating CD34+ cells occurred on day 5 (median 67/microL, range 10-385/mL). The median yield of CD34+ cells was 9.3 (range 3.2-39.1)x10(6)/kg of the recipient's body weight. The median number of T cells in the apheresis products was 3.9 (range 2.7-10.8)x10(8)/kg. Bone pain, headaches and transient elevations of alkaline phosphatase and lactate dehydrogenase were the main adverse events. INTERPRETATION AND CONCLUSIONS: The study shows that collection of allogeneic PBPC after administration of a single dose of pegfilgrastim is feasible. The toxicity profile, graft composition and impact on the recipients' outcome need further investigation.

Adult↗
PubMedDate not supplied

Glycosylated and nonglycosylated recombinant human granulocyte colony-stimulating factor differently modifies actin polymerization in neutrophils.

AIM: Several neutrophil functions can be modified by rhG-CSF administration. Neutrophil morphology changes in the course of treatment with Filgrastim (nonglycosylated rhG-CSF), along with impairment of chemotaxis. Both morphology and chemotaxis are not affected by treatment with Lenograstim (glycosylated rhG-CSF). Thus, we evaluated actin polymerization in neutrophils induced by treatment with the two forms of rhG-CSF. In fact, actin polymerization is crucial for neutrophil motility. MATERIALS AND METHODS: We evaluated twelve healthy subjects undergoing peripheral blood stem cells (PBSC) mobilization for allogeneic transplantation to HLA-identical siblings. Neutrophils were isolated by peripheral venous blood before and after administration of either Filgrastim (six PBSC donors) or Lenograstim (six PBSC donors). Actin polymerization was investigated by a flow cytometric assay, using FITC-phalloidin as a specific probe for F-actin, and two parameters were measured: spontaneous actin polymerization in resting neutrophils; fMLP-stimulated actin polymerization. Results were expressed as relative F-actin content. Fifteen blood donors were studied as a control group. RESULTS: Filgrastim administration induced an increased relative F-actin content in resting neutrophils; however, no further actin polymerization was observed after fMLP stimulation. Neutrophils from subjects treated with Lenograstim showed a normal behaviour in terms of both spontaneous and stimulated actin polymerization. CONCLUSIONS: Glycosylated and nonglycosylated rhG-CSF differently affect actin polymerization in newly generated neutrophils. Such effects may explain some previous findings concerning both morphology and chemotactic properties and may be due to different effects of the two forms of rhG-CSF on proteins involved in neutrophil motility regulation.

Actins↗
PubMedDate not supplied

[G-CSF, neutropenia and candidiasis in VLBW patients].

OBJECTIVES: Relationships among Early Onset Neutropenia (EON), i.e. neutropenia in the first week of life, treated with Filgrastim, and subsequent colonization by Candida spp. with eventual systemic fungal infection in ELBW patients are not clear. We tried to analyze these features in a retrospective study on a selected population of a large tertiary NICU. METHODS: By a database search, we identified a group of VLBW patients who were diagnosed a systemic fungal infection (SFI) during their stay in NICU (n=52), and divided them in two subgroups: those who had presented Early Onset Neutropenia (EON) and thus had been treated with a 3-day course of Filgrastim (n=14)(group A), and those who had not presented EON and thus had not undergone Filgrastim therapy (n=38) (group B). We investigated in both subgroups the following variables: neutrophil count monitoring during the first 2 weeks of life, colonization by Candida spp, day of onset of SFI, outcome. Statistical analysis was performed by Chi-square test, ANOVA and T-test using SPSS 8.0 for Windows. RESULTS: Absolute neutrophil number was obviously lower in group A at recruitment (354/mmc vs 2910\mmc, Chi-square = 9.776, p <0.005), but became normal at the end of G-CSF treatment, thus detecting no significant differences between the two groups at day 8 (p<0.12) and 14 (p<0.34). The onset of SFI occurred significantly earlier ( 9.6 dol vs 14.6 dol., p<0.004) in group A neonates. Fungal Colonization rate in the 2nd week of life was significantly higher in previously neutropenic patients (71% vs. 37%, p< 0.005), who had also a significantly higher number of sites involved (p<0.003). CONCLUSIONS: Neutropenia in the first days of life in VLBW neonates, even if adequately and succesfully treated, heavily influences rates and severity of colonization by fungal spp., and is associated with an earlier onset of a SFI.

Candidiasis↗
PubMed1994

Treatment of clozapine-induced agranulocytosis with recombinant granulocyte colony-stimulating factor.

BACKGROUND: Is clozapine-induced agranulocytosis amenable to treatment with recombinant granulocyte colony-stimulating factor (rG-CSF)? Will this treatment provide benefits in terms of morbidity, mortality, and costs compared with current treatment? METHOD: Five patients with clozapine-induced agranulocytosis (granulocytes < 500/cu mm) were treated with the rG-CSF filgrastim, in addition to standard agranulocytosis therapy protocol. RESULTS: Time from onset until resolution of agranulocytosis was 8.2 +/- 2.1 days compared with a historical study of seven cases where filgrastim was not used and 15.7 +/- 3.7 days were required for resolution. CONCLUSION: rG-CSF (filgrastim) may be an effective and cost-reducing way to provide improved treatment for clozapine-induced agranulocytosis. More research is required.

Adult↗
PubMed1994

Glycosylation of recombinant human granulocyte colony stimulating factor: implications for stability and potency.

The production of recombinant human granulocyte colony stimulating factor (HuG-CSF) by gene cloning has made this growth factor available in large quantities for clinical application. There is accumulating evidence to suggest that the glycosylation of HuG-CSF confers advantages in terms of in vitro stability to temperature, pH and degradation by proteases, and a recent report attributes a greater biological potency, in the absence of larger biological mass, to the property of glycosylation. In this study, the biological potency of glycosylated rHuG-CSF (lenograstim) was compared with that of non-glycosylated rmetHuG-CSF (filgrastim) and a non-glycosylated rHuG-CSF (non-commercial preparation), using duplicate assays of neutrophil and erythroid colony formation in three human bone marrows. Serial doubling dilutions of each rHuG-CSF resulted in a concentration range of 0.008-128 ng/ml. Qualitative (number) and quantitative (size) assessments of colonies were performed at day 14 of culture. Lenograstim proved twice as potent as filgrastim (and non-commercial rHuG-CSF) at maximal colony stimulation, and 20 times more potent than both at half-maximal colony stimulation (P = 0.0001). Incubation with lenograstim also produced a higher proportion of colonies with > 200 cells than either of the other preparations. In conclusion, glycosylated rHuG-CSF (lenograstim) had a greater qualitative and quantitative potency than the non-glycosylated rHuG-CSFs (filgrastim and non-commercial rHuG-CSF), indicating that glycosylation confers a potency advantage on lenograstim.

Colony-Forming Units Assay↗
PubMed1993

Clinical effects of biologic response modifiers.

The clinical use of the biologic response modifiers filgrastim, sargramostim, and regramostim is reviewed. All circulating blood cells are derived from totipotent hematopoietic stem cells. Various biologic response modifiers, including lymphokines and colony-stimulating factors, regulate and activate the lymphoid and myeloid cells of the blood. One of the more important types of blood cell for fighting infection is the neutrophil. Patients with low neutrophil concentrations are at high risk of developing neutropenic fevers and infections. The colony-stimulating factors filgrastim, sargramostim, and regramostim increase the production of circulating neutrophils, and this action is clinically useful in patients undergoing myelosuppressive antineoplastic therapy or bone marrow transplantation and in patients with the acquired immunodeficiency syndrome. Clinical studies of these agents in comparison with antimicrobial prophylaxis or placebo have shown a decreased rate of neutropenic-associated hospitalizations and infections. These agents are also under study for dose intensification of antineoplastics in patients with various solid tumors and for augmenting patient responses to antimicrobial therapy in situations where there is high risk of morbidity and mortality. Sargramostim and regramostim are both granulocyte-macrophage colony-stimulating factors that differ in their degree of glycosylation and source of production, and at high doses they can cause life-threatening adverse effects because they stimulate the production of a broad range of leukocytes. Filgrastim, which stimulates only the production of neutrophils, has been better tolerated, especially at higher doses. Biologic response modifiers hold much promise for improving therapy of certain clinical conditions by decreasing myelosuppressive complications and enhancing responses to other drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1993

Cost considerations in therapy with myeloid growth factors.

Costs of biologic response modifiers, specifically myeloid growth factors, are discussed relative to cost offsets they may produce in the total amount spent on health care in patients with certain disease states. Even though the biologic response modifiers granulocyte colony-stimulating factor (filgrastim) and granulocyte-macrophage colony-stimulating factor (sargramostim or molgramostim) are similar in name, they are chemically and biologically different. These differences result in different clinical applications. Administered after myelosuppressive antineoplastic therapy, filgrastim decreases the risk of infection. The growth factors may also be useful in patients undergoing bone marrow transplantation, in nonneutropenic patients with bacterial infections, and in patients with other disease states. Although the myeloid growth factors are somewhat expensive in terms of acquisition cost, their use is usually associated with a decrease in the risk of medical complications requiring health care expenditures, often for hospitalizations or antimicrobials. The precise cost of acquiring and administering myeloid growth factors depends on three interdependent variables: the factor used, the dosage of the drug, and the duration of therapy. Cost offsets may be more difficult to define, but they would include direct cost offsets, such as reduced episodes of febrile neutropenia and fewer, less-intense days of hospitalization or treatment. Sargramostim and molgramostim have demonstrated efficacy when given after bone marrow transplantation; filgrastim has been shown to lower infection rates by at least 50% after myelosuppressive antineoplastic therapy and in patients with severe chronic neutropenia.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1996

Paclitaxel and carboplatin in metastatic non-small cell lung cancer: preliminary results of a phase I study.

Given their known activity against non-small cell lung cancer, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin were combined in this phase I study of patients with metastatic disease to determine the maximum tolerated dose and the dose-limiting toxicity of the combination. The initial dose of paclitaxel was fixed at 135 mg/m2 given as a 24-hour infusion with carboplatin administered in escalating doses in cohorts using Calvert's formula-dose (mg) = target AUC x (GFR + 25), where AUC is area under the concentration-time curve and GFR is glomerular filtration rate-based on target AUCs of 5, 7, 9, or 11 mg/mL.min. Dose escalations were based on cycle 1 toxicities. Filgrastim was not administered with the first cycle until two or more patients developed grade 4 or febrile neutropenia at the preceding dose level. Dose-limiting toxicity occurred in two patients at level 2 (cycle 1), and filgrastim was administered thereafter for the next four dose levels. Grade 4 thrombocytopenia was seen at level 4; thus, the carboplatin dose was de-escalated thereafter, and the paclitaxel dose escalated. Rare nonhematologic toxicities include fatigue, diarrhea, and nausea and vomiting. Among the first 30 patients, one had a complete response and 14 had partial responses, for an overall response rate of 50%. The combination of paclitaxel and carboplatin is active in non-small cell lung cancer, and the recommended phase II dose without filgrastim support is paclitaxel 175 mg/m2 via a 24-hour infusion with the carboplatin dose targeted to achieve an AUC of 7 mg/ mL.min.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

A phase II multicenter trial of high-dose sequential chemotherapy and peripheral blood stem cell transplantation as initial therapy for patients with high-risk non-Hodgkin's lymphoma.

The purpose of this study was to evaluate the safety and feasibility of front-line high-dose sequential (HDS) chemotherapy with peripheral blood stem cell (PBSC) transplantation in patients with newly diagnosed high-risk non-Hodgkin's lymphoma (NHL). Thirty-two patients with high-risk NHL (defined by the age-adjusted international index) underwent HDS chemotherapy followed by PBSC transplantation and consolidative radiotherapy. Twenty-eight patients (88%) had intermediate/high grade NHL and four patients (12%) had small noncleaved or lymphoblastic lymphoma. Twenty-four patients were classified as high-intermediate-risk (two risk factors) and eight patients were classified as high-risk (three risk factors). The five phases of HDS (see Fig. 1) consisted of Phase I (adriamycin, vincristine, and prednisone); Phase II (cyclophosphamide, filgrastim [G-CSF], and PBSC harvest); Phase III (methotrexate, leucovorin, vincristine; Phase IV (etoposide, filgrastim [G-CSF]); and Phase V (mitoxantrone, melphalan, autologous peripheral blood stem cell infusion, and filgrastim [G-CSF]). Radiation therapy was given to sites of previous bulk disease, 2400 cGy, (D + 30-100)]. Toxicity, engraftment, hospital utilization, overall survival, and relapse-free survival were evaluated. The high-dose sequential chemotherapeutic regimen was well tolerated. Treatment-related mortality was 6.25% with two deaths occurring secondary to sepsis and one death was caused by progressive disease. The major toxicity in Phase I-IV was grade 3 nausea/vomiting. The major toxicity in Phase V was grade 3 or 4 nausea/vomiting and mucositis. The median follow-up is 18.8 months (range 4-44 months). The overall survival (OS) and relapse-free survival (RFS) at 18 months for all patients were 78% (95% CI 37-90%) and 67% (95% CI 46-88%), respectively. The OS at 18 months for all patients, excluding the four patients with either small noncleaved or lymphoblastic lymphoma, was 82% (95% CI 65-98%) vs. 30% (95% CI 0-86%) (p = 0.0059). One patient in this latter group remains alive at 6 months follow-up. The RFS for all patients, excluding the four patients with either small noncleaved or lymphoblastic lymphoma, was 78% (95% CI 58-97%) vs. 0% (95% CI 0-0%) (p = 0.0004). High-dose sequential chemotherapy with initial PBSC transplantation is well tolerated and appears effective in high-risk NHL. Superior results were noted in patients with intermediate grade versus those with small noncleaved or lymphoblastic NHL.

Adult↗
PubMed1996

Phase I trial of high-dose infusional hydroxyurea, high-dose infusional 5-fluorouracil and recombinant interferon-alpha-2a in patients with advanced malignancies.

The ribonucleotide reductase inhibitor, hydroxyurea (HU), augments the cytotoxic effects of 5-fluorouracil (5FU) in vitro; both drugs are synergistic with interferon-alpha (IFN) in vitro. The aim of this phase I study was to determine the maximal duration of HU, 4.3 g/m2, administered as a parenteral infusion in combination with 5FU, 2.6 g/m2 administered over 24 hrs each week, + IFN, 9 MU, subcutaneously three times per week. There were 26 patients enrolled and evaluable. This included 14 patients with colorectal cancer of whom 13 had been previously treated, and 12 patients with other refractory malignancies (pancreas, cholangiocarcinoma, hepatocellular carcinoma, renal cell carcinoma, and others), of whom 10 were previously untreated. The dose-limiting toxicity of this regimen was myelosuppression. This prohibited dose escalation of HU above the starting dose (24 hrs) on a 6-weeks-on, 2-weeks-off therapy schedule. When filgrastim, 480 microg, was administered subcutaneously on days 3-6, the duration of HU could be extended to 48 hrs on a 2-weeks-on, 1-week-off therapy schedule. There were two instances of fatal infection, one in a patient with a rectovaginal fistula with neutropenic sepsis and the second in a patient with non-neutropenic Clostridium septicum sepsis. All therapy was administered in the ambulatory setting. There were three responders, all among previously untreated patients. High-dose parenteral hydroxyurea, 4.3 g/m2 administered over 24 hrs, can be safely combined with high-dose weekly 5FU, 2.6 g/m2 over 24 hrs + IFN, 9 MU subcutaneously three times per week, without filgrastim in the ambulatory setting. Parenteral hydroxyurea, 4.3 g/m2 over 24 hrs daily x 2 can also be combined with high-dose 5FU + IFN, but requires the addition of filgrastim to avoid severe myelosuppression.

Adult↗
PubMed2005

A phase II trial of docetaxel and vinorelbine in patients with hormone-refractory prostate cancer.

Recent studies of docetaxel have demonstrated improved survival over mitoxantrone and prednisone in patients with hormone-refractory prostate cancer (HRPC), supporting the study of novel docetaxel-containing regimens as primary therapy or following initial docetaxel-based therapy. To evaluate the combination of docetaxel and vinorelbine in the treatment of patients with HRPC, 40 patients with proven adenocarcinoma of the prostate with progressive metastatic disease despite androgen ablation were enrolled onto this phase II trial. Patients were treated with docetaxel 60 mg/m2 on day 1 and vinorelbine 15 mg/m2 on days 1 and 8 of a 21-day cycle. All patients received dexamethasone 8 mg twice daily for 4 days starting 1 day prior to the docetaxel infusion. After the first three patients were enrolled, filgrastim was added on days 2-6 and 9-13. Of the 40 patients enrolled, 19 had no prior chemotherapy and 21 had received at least one prior chemotherapy regimen. Of the 19 patients without prior chemotherapy and the 21 with prior chemotherapy, 7 (37%) and 6 (29%) , respectively, demonstrated a decrease in prostate specific antigen by > 50% maintained for at least 4 weeks. Out of eight patients with measurable disease, one achieved a partial response and four demonstrated stable disease. There was one patient with deep vein thrombosis, and febrile neutropenia was noted in only three patients after the protocol was modified to include filgrastim support. The combination of docetaxel and vinorelbine with filgrastim was well tolerated and active against HRPC in patients with or without prior chemotherapy.

Adenocarcinoma↗
PubMed2005

Phase I/II dose escalation study of angiotensin 1-7 [A(1-7)] administered before and after chemotherapy in patients with newly diagnosed breast cancer.

PURPOSE: Multilineage cytopenias occur following myelosuppressive chemotherapy. Most hematopoietic agents differentiate along a single lineage and fail to prevent progressive cytopenias. Angiotensin 1-7 [A(1-7)] is a hematopoietic agent that stimulates the proliferation of multipotential and differentiated progenitor cells in cultured bone marrow and human cord blood. The purpose of this study was to determine the optimal biologic dose and the maximum tolerated dose of A(1-7). EXPERIMENTAL DESIGN: This study determined the safety and activity of A(1-7) following chemotherapy in patients with breast cancer. Toxicity was assessed by administering A(1-7) daily for 7 days followed by a 7-day washout prior to the first cycle of chemotherapy. Beginning 2 days after chemotherapy and continuing daily for at least 10 days, fifteen patients received five different A(1-7) doses and five patients received filgrastim as a comparator group over three cycles of chemotherapy. RESULTS: No dose-limiting toxicity was observed following A(1-7). The frequency of adverse events was slightly lower in A(1-7) than in filgrastim patients. No patient required a chemotherapy modification due to hematologic toxicity. There was an apparent differential dose-response sensitivity of the various lineages to A(1-7). At a dose of 100 microg/kg, A(1-7) reduced the frequency of grade 2-4 thrombocytopenia, anemia, and grade 3-4 lymphopenia as compared to filgrastim. CONCLUSION: These data suggest that A(1-7) may be beneficial in attenuating multilineage cytopenias following chemotherapy at a dose of 100 mug/kg per day.

Adult↗
PubMed1993

Outcome measurement in economic evaluations of growth factors.

There are several ways of measuring outcome in an economic evaluation of filgrastim therapy. These measures imply different types of economic evaluation. In all cases, the filgrastim therapy is compared with no filgrastim therapy. Since different therapeutic strategies are connected with uncertain consequences, decision trees are helpful analytical tools. The potential implications of different types of economic evaluations are illustrated with a simple decision tree.

Cost of Illness↗
PubMed2006

Randomised trial: survival benefit and safety of adjuvant dose-dense chemotherapy for node-positive breast cancer.

We evaluated the survival benefit, safety, feasibility, and tolerability of dose-dense (DD) adjuvant chemotherapy with epirubicin and paclitaxel for women with node-positive primary breast cancer. Randomised patients (n=216) received DD or conventional-schedule (CS) chemotherapy. Dose-dense regimen patients (n=108) received epirubicin 90 mg m-2 plus paclitaxel 175 mg m-2 in four 14-day cycles, then cyclophosphamide 600 mg m-2, methotrexate 40 mg m-2, and fluorouracil 600 mg m-2 (CMF 600/40/600) in three 14-day cycles, plus filgrastim 5 microg kg day-1 as growth support in every cycle. Conventional-schedule regimen patients (n=108) received epirubicin 90 mg m-2 plus cyclophosphamide 600 mg m-2 in four 21-day cycles, then CMF 600/40/600 in three 21-day cycles, plus filgrastim if required. After a median follow-up of 38.4 months, 71 patients (33%) relapsed or died: DD, 33 patients (15 deaths); CS, 38 patients (22 deaths). Dose dense showed a trend for improved disease-free survival (DFS) and overall survival (OS). Four-year rates of DFS and OS were 64 and 85% for DD, and 58 and 75% for CS. All seven cycles were administered to 208 patients (96%). Rates of cycle delay, discontinuation, dose reduction, and adverse events were similar in both groups. Dose-dense sequential chemotherapy with epirubicin/paclitaxel then CMF, supported by filgrastim, is safe and improves survival for patients with node-positive breast cancer.

Adult↗
PubMed1999

The predictive value of white cell or CD34+ cell count in the peripheral blood for timing apheresis and maximizing yield.

BACKGROUND: The collection of peripheral blood stem and progenitor cells (PBPCs) for transplantation can be time-consuming and expensive. Thus, the utility of counting CD34+ cells and white cells (WBCs) in the peripheral blood was evaluated as a predictor of CD34+ cell yield in the apheresis component. STUDY DESIGN AND METHODS: The WBC and CD34+ cell counts in the peripheral blood and the apheresis components from 216 collections were assessed. Sixty-three patients underwent mobilization with chemotherapy plus filgrastim, and 17 patients and 14 allogeneic PBPC donors did so with filgrastim alone. The relationship between the number of WBC and CD34+ cells in the peripheral blood and in the apheresis component was analyzed by using rank correlation and linear regression analysis. RESULTS: The correlation coefficient for CD34+ cells per liter of peripheral blood with CD34+ cell yield (x 10(6)/kg) was 0.87 (n = 216 collections). This correlation existed for many patient and collection variables. However, patients with acute myeloid leukemia had fewer CD34+ cells in the apheresis component at any level of peripheral blood CD34+ cell count. Components collected from patients with CD34+ cell counts below 10 x 10(6) per L in the peripheral blood contained a median of 0.75 x 10(6) CD34+ cells per kg. When the WBC count in the blood was below 5.0 x 10(9) per L, the median number of CD34+ cells in the peripheral blood was 5.6 x 10(6) per L (range, 1.0-15.5 x 10(6)/L). A very poor correlation was found between the WBC count in the blood and the CD34+ cell yield (p = 0.12, n = 158 collections). CONCLUSION: The number of CD34+ cells, but not WBCs, in the peripheral blood can be used as a predictor for timing of apheresis and estimating PBPC yield. This is a robust relationship not affected by a variety of patient and collection factors except the diagnosis of acute myeloid leukemia. Patients who undergo mobilization with chemotherapy and filgrastim also should undergo monitoring of peripheral blood CD34+ cell counts, beginning when the WBC count in the blood exceeds 1.0 to 5.0 x 10(9) per L.

Adolescent↗
PubMed1996

Phase I and pharmacologic study of sequences of paclitaxel and cyclophosphamide supported by granulocyte colony-stimulating factor in women with previously treated metastatic breast cancer.

PURPOSE: Pacltaxel is active in metastatic breast cancer, but limited information is available on combinations of this agent with other cytotoxic agents. Study aims were to determine the maximum-tolerated doses (MTDs) of paclitaxel (24-hour infusion) and cyclophosphamide (1-hour infusion) administered every 21 days with granulocyte colony-stimulating factor (G-CSF, filgrastim) to determine the effect of drug sequence on toxicity and pharmacology and to evaluate the activity of this combination in women with anthracycline-resistant disease. PATIENTS AND METHODS: Thirty-seven women with metastatic breast cancer were treated. Starting doses were paclitaxel 135 mg/m2 and cyclophosphamide 750 mg/m2, with filgrastim 5 microG/kg/d subcutaneously beginning 24 hours after chemotherapy. Four patients were treated at each dose level. The sequence of drug administration was alternated between sequential patients, and with subsequent courses of therapy in each patient, to enable evaluation of effects of drug sequence on toxicity and pharmacology. Patients were treated every 21 days and disease status was reevaluated every two courses. RESULTS: Paclitaxel 200 mg/m2 and cyclophosphamide 1,250 mg/m2 is the MTD for this combination on this schedule. The hematopoietic toxicity of therapy was sequence-dependent. Paired analysis of toxicity data indicated more severe toxicity in courses in which paclitaxel was administered first. Sequence-dependent pharmacologic effects did not account for this phenomenon. Responses were noted in 29% of patients with anthracycline-resistant disease. CONCLUSION: Paclitaxel 200 mg/m2 and cyclophosphamide 1,250 mg/m2 with filgrastim administered every 21 days are the doses recommended for further study.

Adult↗
PubMed1998

Phase I study of topotecan in combination with cyclophosphamide in pediatric patients with malignant solid tumors: a Pediatric Oncology Group Study.

PURPOSE: To determine the maximum-tolerated dose (MTD) and dose-limiting toxicity of topotecan when combined with cyclophosphamide in pediatric patients with recurrent or refractory malignant solid tumors. PATIENTS AND METHODS: A total of 33 patients received cyclophosphamide (250 mg/m2/dose) followed by topotecan in escalating doses (0.6 to 0.75 mg/m2/dose), each given as a 30-minute infusion daily for 5 days. A total of 154 fully assessable treatment courses were given to these patients. RESULTS: Neutropenia was the dose-limiting toxicity of the therapy at both topotecan dose levels. The addition of filgrastim allowed escalation of the topotecan dose to the 0.75-mg/m2 level with acceptable neutropenia. Other significant toxicities were anemia and thrombocytopenia. Nonhematopoietic toxicity of grades > or = 3 was not observed. Responses were reported in patients with Wilms' tumor (one complete response [CR], one partial response [PR]), neuroblastoma (one CR, one PR), rhabdomyosarcoma (one PR), and osteosarcoma (one PR). Pharmacokinetic studies indicate that cyclophosphamide administered on the schedule used in this study did not alter topotecan disposition on day 5. As with previous studies, a pharmacodynamic relation between systemic exposure and myelosuppression was noted. CONCLUSION: The combination of topotecan and cyclophosphamide shows activity in a wide variety of pediatric solid tumors and can be given with acceptable hematopoietic toxicity with the use of filgrastim support. We recommend that pediatric phase II trials use cyclophosphamide 250 mg/m2 followed by topotecan 0.75 mg/m2 daily for 5 days with filgrastim for amelioration of neutropenia.

Adolescent↗