PharmPK Discussion - Inability to reach high dose carboplatin AUC

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On 17 Feb 2000 at 16:59:19, Tong_William/mskcc_MOL.-a-.mskmail.mskcc.org sent the message


      Dear Collegues,

      We have a clinical trial using serum creatinine to targetted
high dose carboplatin AUC, together with cytoxan and etoposide.
Measured AUC is lower than expected at high doses. Possible due to 1.
saturated reabsorption, 2. measurment error due to hydration(urine
output 4-5 liters a day, 2 liters in the first 4 hours)

      Since we measure "concentration" in plasma, if we rapid hydrate
with 1 liter of fluid, the blood volume may change from 5 to 6 liter,
the drug concentration will be about 15% lower than without
hydration. It  is correct if we add a correction factor such as serum
albumin before/after infusion.

      Any suggestion is appreciated.
      Thanks

      Bill Tong
      Memorial Sloan Kettering Cancer Center

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On 18 Feb 2000 at 21:02:36, David_Bourne (david.aaa.boomer.org) sent the message

[Two replies - db]

X-Sender: slowis.-at-.pop3.nildram.co.uk
Date: Fri, 18 Feb 2000 08:46:35 +0000
To: PharmPK.at.boomer.org
From: Stephen Lowis 
Subject: Re: PharmPK Inability to reach high dose carboplatin AUC

Bill,
Isn't it also possible Carboplatin clearance is not being predicted
accurately by serum Creatinine, especially if your patients are
underweight? Do you have data to allow you to compare the Calvert equation
or one of the other GFR based methods?

Stephen Lowis
Macmillan Consultant in
Paediatric and Adolescent Oncology
Department of Paediatric Oncology

Bristol Royal Hospital for Sick Children
St Michael's Hill
Bristol
United Kingdom

Tel     (44)117 928 5521 (Sec)
         (44)117 928 5490 (Direct or Fax)
         (44)117 923 0000 (Bleep)
	(44)13991133 ask for 735115 (Radiopage)
Fax     (44)117 928 5682

spl.aaa.lowis.nildram.co.uk
S.P.Lowis.-a-.bristol.ac.uk

---

X-Sender: n7950211.aaa.popin.ncl.ac.uk
Date: Fri, 18 Feb 2000 16:33:10 +0000
To: PharmPK.-a-.boomer.org
From: James 
Subject: Re: PharmPK Inability to reach high dose carboplatin AUC

Dear Dr Tong,

Assuming you are using the Calvert formula, it is possible that the problem
arises from how you estimate renal function in order to decide what dose to
give.  For example if you are using the Cockcroft & Gault formula, which
estimates creatinine clearance in healthy males rather than GFR in cancer
patients, you will be systematically underdosing and this percentage error
becomes more obvious at high doses.

James Wright

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On 21 Feb 2000 at 22:36:28, Tong_William/mskcc_MOL.at.mskmail.mskcc.org sent the message


     Dear Steve and James,

     There are two systems going on. First is the measurement of
carboplatin AUC. We may have error in measurment, calculation or
sampling problem, but the trend is the AUC starts to be lower at
higher doses. Second is the GFR calculation. We used C and G as well
as Jeliff method using serum creatinine. Since serum creatinine can
be  a function of muscle mass, hepatic function and protein loading.
Are there updated GFR formula? Is there any experience with cystatin
C with carboplatin? There are two publications on CDDP and one on
CDBCA renal reabsroption.

     Bill Tong, MSKCC

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