Second mobilization of peripheral blood progenitor cells in patients with poor first mobilization

Majado, Maria Juliana; Gonzalez, Celia; Marı́n, Luis; Morales, Alfonso; Moya, María Rosa; Candel, R

doi:10.1016/s0041-1345(03)00710-3

Cited by 5 publications

(4 citation statements)

References 9 publications

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“…Although its role in the treatment for ovarian cancer and small-cell lung cancer is declining, CPA continues to be used in treatment of breast cancer as a critical component of the CMF, CEF (CPA, epirubicin, and 5-fluorouracil), MVC (mitoxantrone, vinblastine, and CPA) and TAC (docetaxel, doxorubicin and CPA) regimen [289,290,[309][310][311][312]. Higher doses of CPA are used in the treatment prior to bone marrow transplantation for aplastic anemia, leukemia and other malignancies [11][12][13][14][15][16].…”

Section: Antitumor Activitymentioning

confidence: 99%

“…Recently, CPA given at low doses has gained increased interest as either an antiangiogenic or an immunostimulatory agent in combination with immunotherapies in the treatment of cancer [6][7][8][9][10]. CPA is also used for the mobilization of hematopoietic progenitor cells from the bone marrow into peripheral blood [11][12][13][14][15][16]. Moreover, CPA has been widely used as an immunosuppressive drug in combination with other immunosuppressants such as prednisone, mycophenolic acid, or azathioprine to treat some autoimmune diseases including systemic lupus erythematosus (SLE) [17][18][19][20][21][22][23] and rheumatoid arthritis [24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

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Clinical Pharmacology of Cyclophosphamide and Ifosfamide

Zhang¹,

Tian²,

Zhou³

2006

CDTH

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The oxazaphosphorine cyclophosphamide (CPA) and ifosfamide (IFO) are two commonly used DNAalkylating agents in cancer chemotherapy. This review highlights the pharmacokinetics and pharmacodynamics of the two important agents. As alkylating agents, CPA and IFO are usually combined with other anticancer drugs in the chemotherapy of solid tumors and hematological malignancies to obtain synergistic or additive anticancer effect due to complementary mechanism of action. Both compounds are prodrugs that are activated via 4-hydroxylation by cytochrome P450s such as CYP2B6 and CYP3A4 to generate alkylating nitrogen mustards (phosphoramide mustard and ifosforamide mustard) and the byproduct acrolein. The resultant mustards can alkylate DNA to form DNA-DNA cross-links, leading to inhibition of DNA synthesis and cell apoptosis. Both CPA and IFO are also inactivated by N-dechloroethylation, resulting in N-dechloroethylated metabolites and the byproduct chloroacetaldehyde. Acrolein is the causative agent for hemorrhagic cystitis, whereas chloroacetaldehyde induces nephrotoxicity and neurotoxicity. Pharmacokinetics of CPA and IFO is markedly influenced by route of administration and duration of treatment, age, comedication, liver and renal function. Large interpatient variability in pharmacokinetics, clinical response rate and toxicity has been observed in cancer patients treated with CPA or IFO. Resistance to CPA or IFO occurs due to decreased activation by CYP3A4 and CYP2B6, increased deactivation of the agents, decreased entry into or increased efflux from tumor cells, increased cellular thiol level, increased DNA repair capacity, and/or deficient apoptotic response to DNA damage. A full understanding of factors affecting the pharmacokinetics, pharmacodynamics, toxicology and pharmacogenetics of CPA and IFO is important to optimize the dose and regimens of CPA and IFO in cancer chemotherapy.

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Section: Antitumor Activitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical Pharmacology of Cyclophosphamide and Ifosfamide

Zhang¹,

Tian²,

Zhou³

2006

CDTH

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“…Cyclophosphamide (Cytoxan; CTX) is one of the most widely used alkylating agents in the treatment of haematological malignancies and a variety of solid tumours, including leukaemia, ovarian cancer, and small‐cell lung cancer [1]. In addition, high‐dose regimens of CTX are frequently used prior to bone marrow transplantation in patients with aplastic anaemia, leukaemia, or other malignancies for mobilization of haematopoietic progenitor cells from the bone marrow into peripheral blood [2, 3]. Moreover, CTX has been widely used as an immunosuppressive agent in the treatment of several autoimmune diseases, including systemic lupus erythematosus (SLE) [4] and rheumatoid arthritis [5].…”

Section: Introductionmentioning

confidence: 99%

Relationship of glutathione S‐transferase genotypes with side‐effects of pulsed cyclophosphamide therapy in patients with systemic lupus erythematosus

Zhong

Huang

Yang

et al. 2006

Brit J Clinical Pharma

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AimsCyclophosphamide (CTX) is an established treatment of severe systemic lupus erythematosus (SLE). Cytotoxic CTX metabolites are mainly detoxified by multiple glutathione S-transferases (GSTs). However, data are lacking on the relationship between the short-term side-effects of CTX therapy and GST genotypes. In the present study, the effects of common GSTM1 , GSTT1, and GSTP1 genetic mutations on the severity of myelosuppression, gastrointestinal (GI) toxicity, and infection incidences induced by pulsed CTX therapy were evaluated in patients SLE.Methods DNA was extracted from peripheral leucocytes in patients with confirmed SLE diagnosis ( n = 102). GSTM1 and GSTT1 null mutations were analyzed by a polymerase chain reaction (PCR)-multiplex procedure, whereas the GSTP1 codon 105 polymorphism (Ile → Val) was analyzed by a PCR-restriction fragment length polymorphism (RFLP) assay. ResultsOur study demonstrated that SLE patients carrying the genotypes with GSTP1 codon 105 mutation [ GSTP1 *-105I/V (heterozygote) and GSTP1 *-105 V/V (homozygote)] had an increased risk of myelotoxicity when treated with pulsed high-dose CT X therapy (Odds ratio (OR) 5.00, 95% confidence interval (CI) 1.96, 12.76); especially in patients younger than 30 years (OR 7.50, 95% CI 2.14, 26.24), or in patients treated with a total CTX dose greater than 1.0 g (OR 12.88, 95% CI 3.16, 52.57). Similarly, patients with these genotypes ( GSTP1 *I/V and GSTP1 *V/V) also had an increased risk of GI toxicity when treated with an initial pulsed high-dose CT X regimen (OR 3.33, 95% CI 1.03, 10.79). However, GSTM1 and GSTT1 null mutations did not significantly alter the risks of these short-term side-effects of pulsed high-dose CTX therapy in SLE patients. ConclusionsThe GSTP1 codon 105 polymorphism, but not GSTM1 or GSTT1 null mutations, significantly increased the risks of short-term side-effects of pulsed high-dose CTX therapy in SLE patients. Because of the lack of selective substrates for a GST enzyme phenotyping study, timely detection of this mutation on codon 105 may assist in optimizing pulsed high-dose CTX therapy in SLE patients. Correspondence

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“…Recently, CPA given at low doses has gained increased interest as either an antiangiogenic or an immuno-stimulatory agent in combination with immunotherapies in treatment of cancer [44][45][46][47][48]. CPA given at high doses is also used in treatment of aplastic anemia, leukemia and other malignancies for the mobilization of hematopoietic progenitor cells from the bone marrow into peripheral blood prior to bone marrow transplantation [13,14,[49][50][51][52]. The tumor cell killing and apoptosis-inducing effects of oxazaphosphorines are generally considered to result from DNA crosslink formation through covalent bonding of highly reactive alkyl groups of the alkylating nitrogen mustards, resulting from oxazaphosphorines with specific nucleophilic groups of DNA molecules [53][54][55][56][57][58][59][60].…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Design of New Oxazaphosphorine Anticancer Drugs

Liang¹,

Huang²,

Duan³

et al. 2007

CPD

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The oxazaphosphorines including cyclophosphamide (CPA, Cytoxan, or Neosar), ifosfamide (IFO, Ifex) and trofosfamide (Ixoten) represent an important group of therapeutic agents due to their substantial antitumor and immunomodulating activity. However, several intrinsic limitations have been uncounted during the clinical use of these oxazaphosphorines, including substantial pharmacokinetic variability, resistance and severe host toxicity. To circumvent these problems, new oxazaphosphorines derivatives have been designed and evaluated with an attempt to improve the selectivity and response with reduced host toxicity. These include mafosfamide (NSC 345842), glufosfamide (D19575, beta-D-glucosylisophosphoramide mustard), S-(-)-bromofosfamide (CBM-11), NSC 612567 (aldophosphamide perhydrothiazine) and NSC 613060 (aldophosphamide thiazolidine). Mafosfamide is an oxazaphosphorine analog that is a chemically stable 4-thioethane sulfonic acid salt of 4-hydroxy-CPA. Glufosfamide is IFO derivative in which the isophosphoramide mustard, the alkylating metabolite of IFO, is glycosidically linked to a beta-D-glucose molecule. Phase II studies of glufosfamide in the treatment of pancreatic cancer, non-small cell lung cancer (NCSLC), and recurrent glioblastoma multiform (GBM) have recently completed and Phase III trials are ongoing, while Phase I studies of intrathecal mafosfamide have recently completed for the treatment of meningeal malignancy secondary to leukemia, lymphoma, or solid tumors. S-(-)-bromofosfamide is a bromine-substituted IFO analog being evaluated in a few Phase I clinical trials. The synthesis and development of novel oxazaphosphorine analogs with favourable pharmacokinetic and pharmacodynamic properties still constitutes a great challenge for medicinal chemists and cancer pharmacologists.

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Second mobilization of peripheral blood progenitor cells in patients with poor first mobilization

Cited by 5 publications

References 9 publications

Clinical Pharmacology of Cyclophosphamide and Ifosfamide

Clinical Pharmacology of Cyclophosphamide and Ifosfamide

Relationship of glutathione S‐transferase genotypes with side‐effects of pulsed cyclophosphamide therapy in patients with systemic lupus erythematosus

Design of New Oxazaphosphorine Anticancer Drugs

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