Bioavailability of Cyclophosphamide in the CMF Regimen

Gheuens, Eric; Slee, P.H.Th.J.

doi:10.1159/000216759

Cited by 12 publications

(10 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This compound is then transported to target tissues and transformed into phosphoramide mustard on entering cells, which produces cytotoxic events by alkylating nuclear DNA 2,3 . For some clinical indications, cyclophosphamide is given in small oral doses repeated once daily in combination with other chemotherapy drugs and supportive care medications 4–6 . Recently, a totally oral combination regimen used in cancer chemotherapy, comprising of daily oral cyclophospamide and capecitabine, has been investigated in clinical trial centres in New Zealand and Australia.…”

Section: Introductionmentioning

confidence: 99%

Application of liquid chromatography–mass spectrometry to monitoring plasma cyclophosphamide levels in phase I trial cancer patients*

Liu¹,

Kestell

Findlay

et al. 2004

Clin Exp Pharma Physio

View full text Add to dashboard Cite

A specific and efficient liquid chromatography-mass spectrometry (LC-MS) method was established for monitoring patient plasma cyclophosphamide levels in a phase I trial of an oral cyclophosphamide-based combination chemotherapy regimen. An Agilent 1100 Series LC-MSD system (Agilent Technologies, Avondale, PA, USA), with a single quadrupole mass detector using a positive atmospheric pressure chemical ionization (APCI) interface and single ion monitoring at m/z 261, was used. Chromatography was performed using a LUNA C8 5 microm 30 x 4.6 mm stainless steel column (Phenomenex, Torrance, CA, USA) and a mobile phase of aqueous acetonitrile pumped at a flow rate of 0.7 mL/min. High-throughput solid-phase sample extraction was performed using a Gilson ASPEC XL4 system (Gilson Medical, Middleton, WI, USA) controlled by prestored programs. The standard curve for cyclophosphamide was linear over the concentration range 0.026-1.08 microg/mL (r(2) > 0.994). Intra- and interassay accuracy and precision were 97-107 and 3-10%, respectively. The limit of detection was determined to be 0.01 microg/mL. Single ion monitoring at m/z 261 provided a high degree of specificity without interference from the matrix or other chemotherapy drugs. Automated sample processing allowed the analysis of a large number of plasma samples from a clinical trial of repeated daily oral dosing of cyclophosphamide. One hour after dosing, cyclophosphamide was detected in 98 of 106 plasma specimens at concentrations ranging between 0.03 and 4.88 microg/mL. Twenty-four hours after dosing, cyclophosphamide was detected in 72 of 77 plasma specimens at concentrations ranging between 0.06 and 3.13 microg/mL. There were no time-dependent changes in cyclophosphamide concentration during the 43 day period of repeated daily oral dosing. There was no correlation between cyclophosphamide dose and plasma concentration, despite the wide range of doses given in the clinical trial (50-125 mg/m(2)). We conclude that a solid-phase extraction LC-MS technique was validated for determining cyclophosphamide in human plasma. Interoccasion variability in the rate of oral absorption and in the clearance of systemically available drug may have contributed to the wide range of cyclophosphamide concentrations found at 1 and 24 h after tablet ingestion.

show abstract

Section: Introductionmentioning

confidence: 99%

Application of liquid chromatography–mass spectrometry to monitoring plasma cyclophosphamide levels in phase I trial cancer patients*

Liu¹,

Kestell

Findlay

et al. 2004

Clin Exp Pharma Physio

View full text Add to dashboard Cite

show abstract

“…MTX, 5-fluorouracil (5-FU) and CY are used in monotherapy, but are also applied in var ious antineoplastic regimens [4][5][6], Undesira ble effects common for these cytostatic agents are bone marrow damage and alimentary tract damage. Nephrotoxicity is revealed when MTX and CY are given, though the mechanism of renal damage is different [7, 8J.…”

mentioning

confidence: 99%

Effect of Some Anticancer Drugs and Combined Chemotherapy on Renal Toxicity

Skrętkowicz

Sekulska²,

Danilewicz³

et al. 1996

Neurosignals

View full text Add to dashboard Cite

The nephrotoxic action of anticancer drugs such as nitrogranulogen (NG), methotrexate (MTX), 5-fluorouracil (5-FU) and cyclophosphamide (CY) administered alone or in combination [MTX+5-FU+CY (CMF)] was evaluated in experiments on Wistar rats. After drug administration, creatinine concentrations in the plasma and in the urine of the rats were determined, as well as creatinine clearance. Histopathologic evaluation of the kidneys was also performed. After MTX administration a significant increase (p = 0.0228) in the plasma creatinine concentration and a significant (p = 0.0001) decrease in creatinine clearance was noted compared to controls. After the administration of NG, 5-FU and CY neither a statistically significant increase in creatinine concentration nor an increase in creatinine clearance was observed compared to the group receiving no cytostatics. Following polytherapy according to the CMF regimen, a statistically significant decrease (p = 0.0343) in creatinine clearance was found, but creatinine concentration did not increase significantly compared to controls. CY caused hemorrhagic cystitis in 40% of rats, but it did not cause this complication when combined with 5-FU and MTX. Histologic changes were found in rat kidneys after administration of MTX, CY and NG, while no such change was observed after 5-FU and joint administration of MTX+5-FU+CY compared to controls. Our studies indicate that nephrotoxicity of MTX + 5-FU+CY administered jointly is lower than in monotherapy.

show abstract

“…In the same study, there was 22% interindividual variability in clearance of the cyclophosphamide metabolite 4-0-hydroxycyclophosphamide 71. It is believed that both body weight and age have an impact on cyclophosphamide PK, with younger patients having a faster cyclophosphamide half-life 72,73. The PG of cyclophosphamide have not been studied extensively because it is commonly used in combination with other chemotherapeutic agents 74…”

Section: Cancer Therapeuticsmentioning

confidence: 99%

Pharmacogenetics in breast cancer: steps toward personalized medicine in breast cancer management

Rofaiel

Muo²,

Mousa

2010

PGPM

View full text Add to dashboard Cite

There is wide individual variability in the pharmacokinetics, pharmacodynamics, and tolerance to anticancer drugs within the same ethnic group and even greater variability among different ethnicities. Pharmacogenomics (PG) has the potential to provide personalized therapy based on individual genetic variability in an effort to maximize efficacy and reduce adverse effects. The benefits of PG include improved therapeutic index, improved dose regimen, and selection of optimal types of drug for an individual or set of individuals. Advanced or metastatic breast cancer is typically treated with single or multiple combinations of chemotherapy regimens including anthracyclines, taxanes, antimetabolites, alkylating agents, platinum drugs, vinca alkaloids, and others. In this review, the PG of breast cancer therapeutics, including tamoxifen, which is the most widely used therapeutic for the treatment of hormone-dependent breast cancer, is reviewed. The pharmacological activity of tamoxifen depends on its conversion by cytochrome P450 2D6 (CYP2D6) to its abundant active metabolite, endoxifen. Patients with reduced CYP2D6 activity, as a result of either their genotype or induction by the coadministration of other drugs that inhibit CYP2D6 function, produce little endoxifen and hence derive limited therapeutic benefit from tamoxifen; the same can be said about the different classes of therapeutics in breast cancer. PG studies of breast cancer therapeutics should provide patients with breast cancer with optimal and personalized therapy.

show abstract

Bioavailability of Cyclophosphamide in the CMF Regimen

Cited by 12 publications

References 5 publications

Application of liquid chromatography–mass spectrometry to monitoring plasma cyclophosphamide levels in phase I trial cancer patients*

Application of liquid chromatography–mass spectrometry to monitoring plasma cyclophosphamide levels in phase I trial cancer patients*

Effect of Some Anticancer Drugs and Combined Chemotherapy on Renal Toxicity

Pharmacogenetics in breast cancer: steps toward personalized medicine in breast cancer management

Contact Info

Product

Resources

About