DOSECHECK™

Improved efficacy and safety of fluorouraciltherapy with the help of a simple blood test

DoseCheck™ is a blood testing service intended to aid optimisation of Fluorouracil (5-FU) based treatment of cancer patients. DoseCheck™ is used when 5-FU is administered as continuous infusion.

5-FU is included in several continuous infusion regimens to treat different solid tumour cancers, e.g. bowel and stomach cancers. The aim is to reach blood levels that are as high as possible, but without causing high grade toxicity. In the absence of a suitable method in clinical practice for measurement of 5-FU plasma levels, the dosing has traditionally been based on Body Surface Area (BSA). However, it is well established  that 5-FU dosing based on BSA can result in >10 -fold differences in plasma 5-FU levels between different individuals.
This results from a variety of factors including patient's genetic makeup, diet, general health, concomitant medications, etc. The reliance on BSA is a cause for concern for many oncologists responsible for chemotherapy because incorrect plasma 5-FU level may result in suboptimal efficacy or toxicity. Studies have shown that > 80% of cancer patients may
receive suboptimal levels of 5-FU.

Table 1. Examples of chemotherapy regimens that include continuous infusion of 5-FU.

*  Also called the deGramont Regimen

DoseCheck™ can now change this. DoseCheck™ is available to measure patients' 5-FU plasma levels at a reasonable cost, and with a typical turnaround time of only 5-7 days. DoseCheck™ service, which uses a CE marked test, is exclusively available from Lab21 Healthcare in the UK, Ireland and the Middle East.

 

Benefits of using DoseCheck™
How does DoseCheck™ work?
DoseCheck™ sample collection
How to order DoseCheck ™
Published references

 

Benefits of using DoseCheck™ back to top

Adjusted dosing of 5-FU has been shown to achieve improved efficacy and reduced toxicity compared to fixed, BSA-based dosing.

A recent study, published by Gamelin et al, 2008, is a good example. In this study, patients with metastatic colorectal cancer were treated with weekly 8-hour infusions of 5-FU, combined with leucovorin. Patients were either given a fixed, BSA-based 1,500 mg/m² dosage of 5-FU throughout the treatment, or their 5-FU dosage was adjusted after each cycle until the plasma 5- FU level reached the optimal range. This study showed that adjustment of 5-FU dosage based on measurement of its level in the plasma achieved significantly improved efficacy and reduced toxicity of the infusion treatment (Figures 1-3).

Figure 1. The 5-FU dosage required to achieve the optimal 5-FU level in plasma ranged from 765 to 2,200 mg/m², with a mean dosage of 1,790 mg/m².

Figure 2. Adjusted 5-FU dosage achieved improved overall response rate and survival compared to fixed 5-FU dosage based on BSA.

Figure 3. Adjusted 5-FU dosage reduced some side effects, especially diarrhea, compared to fixed dosage of 5-FU.

 

How does DoseCheck™ work? back to top

DoseCheck™ is used to adjust 5-FU dosage after the first treatment cycle.

1st treatment cycle:

• 5-FU dosage is calculated based on BSA. DoseCheck™ Steady State blood sample is taken for 5-FU measurement.

• DoseCheck™ report is used to adjust 5-FU dosage for the next cycle.

                 

Further treatment cycles:

The initial 5-FU dosage is adjusted based on DoseCheck™ results, until optimal 5-FU blood level is reached.

 

DoseCheck™ report:

The report includes 5-FU concentration (µg/L) in the Steady State plasma sample. It also includes the Area Under the Curve (mg•h/L) for total 5-FU dosage in the treatment cycle.

AUC (mg•h/L) = 5-FU (µg/L) x h

AUC = Area Under the Curve
5-FU = 5-FU plasma concentration
h = Total 5-FU infusion time in the treatment cycle

Based on several studies, the optimal AUC for
5-FU is 20-24 mg•h/L (Gamelin et al, 1999 &
1998; Ychou et al, 2003).

Please click here to see a DoseCheck™ report.

DoseCheck™ report includes a chart to aid follow-up of patients’ 5-FU dosing and the corresponding 5-FU AUC values (Figure 4).

Figure 4. Example of a follow-up chart for a patient’s 5-FU dosing and the corresponding 5-FU AUC values during cancer treatment.

DoseCheck™ report also includes a table (Table 1), for guidance on how the 5-FU dose may be adjusted based on the 5-FU AUC result given by DoseCheck™.  The table is based on a 5-FU AUC target range of 20-24 mg•h/L, based on studies on colorectal cancer (Gamelin et al, 2008; Ychou et al, 2003; Gamelin et al, 1998; Gamelin et al, 1996).

Table 1.  A guidance table for 5-FU dose adjustment. 5-FU dose adjustment is always the responsibility of the doctor. This table below is adjusted from Gamelin et al, 2008.

DoseCheck™ sample collection back to top

Please click here for DoseCheck™ Sample Collection Guide.

Only one Steady State sample is required in one treatment cycle, even if 5-FU infusion is split into two sessions.

How to order DoseCheck™ back to top
To order DoseCheck™, please contact Lab21
customer services by telephone: +44 (0)1223
395450), fax: +44 (0)1223 395451 or email:
dosecheck@lab21.com.

Published references back to top

• Gamelin E, Delva R, Jacob J, et al. Individual fluorouracil dose adjustment based on pharmacokinetic follow-up compared with conventional dosage: Results of a multicenter randomized trial of patients with metastatic colorectal cancer. J Clin Oncol. 2008; 26(13): 2099-2104.
• Gamelin E and Boisdron-Celle M. Dose monitoring of 5-Fluorouracil in patients with colorectal or head and neck cancers - status of the art. Critic Rev Oncol/Hematol, 1999; 30: 71-79.
• Undevia SD et al. Pharmacokinetic variability of anticancer agents. Nature Rev Cancer  2005; 5: 447-458.
• Gamelin E et al. Long-term weekly treatment of colorectal metastatic cancer with fluorouracil and leucovorin: results of a multicentric prospective trial of fluorouracil dosage optimization by pharmacokinetic monitoring in 152 patients. J Clin Oncol, 1998: 16:1470-1478.
• Ychou M et al. Individual 5-FU dose adaptation in metastatic colorectal cancer: results of a phase II study using a bimonthly pharmacokinetically intensified L V5FU2 regimen. Cancer Chemother Pharmacol 2003;52(4):282-90.
• LymanGH, Dale DC, Crawford J.

• Incidence and predictors of low dose-intensity in adjuvant breast cancer chemotherapy: a nationwide study of community practices. J Clin Oncol. 2003; 21 (24): 4524-4531.

• McDonald GB, Slattery JT, Bouvier ME, et al. Cyclophosphamide metabolism, liver toxicity, and mortality following hematopoietic stem cell transplantation. Blood. 2003; 101(5): 2043-2048.
• Partridge AH, Avorn J, Wang PS, Winer EP.

• Adherence to therapy with oral antineoplastic agents. J Nat Cancer Inst. 2002; 94(9): 652-661.

• Hon YY, Evans WE. Making TOM work to optimize cancer chemotherapy: a multidisciplinary team approach. Clin Chern. 1998; 44(2): 388-400.
• Krynetski EY, Evans WE. Pharmacogenetics of cancer therapy: getting personal. Am J Hum Genet. 1998; 63(1):11-16.
• Milano G et al. Relationship between fluorouracil systemic exposure and tumor response and patient survival. J Clin Oncol. 1994; 12 (6): 1291 -1295.