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NDT Advance Access originally published online on August 25, 2006
Nephrology Dialysis Transplantation 2007 22(1):289-290; doi:10.1093/ndt/gfl498
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Pharmacokinetic analysis of docetaxel during haemodialysis in a patient with locally advanced non-small cell lung cancer

Email: wolfgang.hilbe{at}uibk.ac.at

Sir,

Management of localized stage III non-small cell lung cancer (NSCLC) patients has improved significantly in recent years. Nevertheless, there exist few case reports about chemotherapeutic regimens of patients with end-stage renal disease (ESRD) and NSCLC [1,2]. Docetaxel (DXL) in combination with carboplatin is successfully used in the treatment of NSCLC [3], but there are no reports on the treatment of haemodialysis (HD) patients with NSCLC.

Here, we report on a patient with a NSCLC, who developed ESRD after two cycles of chemotherapy with a gemcitabine/platinum combination. Because of the good performance status of the patient and the chemo-sensitivity of the tumour, treatment was completed with DXL 65 mg/m2 and carboplatin 200 mg/m2 on day 1 and day 21 with sequential radiotherapy. DXL was infused over 1 h, followed by carboplatin infusion over 1 h. HD was immediately performed after the end of carboplatin application. Total plasma concentrations of DXL were evaluated in the blood samples collected 1,3 and 5 h after the end of the DXL infusion, using solid phase extraction and high-performance liquid chromatography. Pharmacokinetic analysis of DXL revealed a rapid decrease of plasma concentrations immediately after administration. Only very low amounts of DXL—comparable with plasma concentrations of patients without renal failure—were detected 1 h after the end of the infusion of 65 mg/m2 DXL (Figure 1), suggesting that DXL is rapidly bound to plasma proteins as described before [4]. DXL was not dialysed, since increased concentrations were found in plasma samples collected from the venous line compared with samples collected from the arterial line (Figure 1A). Interestingly, even lower amounts of DXL in the blood were found after the second cycle of DXL (Figure 1B). This observation could be explained by the rapid half-life of DXL (about 4 min) causing no accumulation of the drug in the central compartment after repeated administration. So these differences in DXL plasma concentrations looked accidental. The observed transient increase of DXL plasma concentrations during HD is probably due to altered protein binding of the drug. To evaluate DXL toxicity, blood-count controls were taken in periodic intervals. Grade 2 leuco- and thrombocytopaenia (National Cancer Institute Common Toxicity Criteria, NCI–CTC) were detected 10–20 days after the second cycle of chemotherapy (data not shown).


Figure 1
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  		Fig. 1. Pharmacokinetic analysis of DXL. Plasma samples taken before and after the HD capillary were taken 1, 3 and 5 h after the end of DXL infusion. Samples were analysed by HPLC for the total plasma concentration of DXL. (A) DXL plasma levels in samples taken from the arterial (white) and venous line (black). (B) DXL plasma levels taken from the venous line during HD after the first (black) and second cycle of chemotherapy (white).

 
Restaging at day 42 revealed further regression of the central tumour and a decreased bronchial wall thickness. The mediastinal lymph nodes remained stable and a restaging mediastinoscopy showed necrosis but also residual tumour cells. Afterwards, sequential radiotherapy of the mediastinum and the primary completed the treatment.

In conclusion, a carboplatin/DXL combination might be a suitable regimen for NSCLC patients undergoing HD.

Conflict of interest statement. None declared.

Kathrin Hochegger1, Karl Lhotta1, Gert Mayer1, Martin Czejka2 and Wolfgang Hilbe3

1Innsbruck Medical University
Clinical Division of Nephrology
Innsbruck
2Vienna Medical University
Department of Clinical Pharmacy and Diagnostics
Vienna
3Innsbruck Medical University
Clinical Division of General Internal Medicine
Innsbruck
Austria

References

  1. Watanabe R, Takiguchi Y, Moriya T, et al. (2003) Feasibility of combination chemotherapy with cisplatin and etoposide for haemodialysis patients with lung cancer. Br J Cancer 88:25–30.[CrossRef][Web of Science][Medline]
  2. Inoue A, Saijo Y, Kikuchi T, et al. (2004) Pharmacokinetic analysis of combination chemotherapy with carboplatin and etoposide in small-cell lung cancer patients undergoing hemodialysis. Ann Oncol 15:51–54.[Abstract/Free Full Text]
  3. Rigas JR and Lara PN Jr. (2005) Current perspectives on treatment strategies for locally advanced, unresectable stage III non-small cell lung cancer. Lung Cancer 50:Suppl 2, S17–S24.
  4. Clarke SJ and Rivory LP. (1999) Clinical pharmacokinetics of docetaxel. Clin Pharmacokinet 36:99–114.[CrossRef][Web of Science][Medline]

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This Article
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