A Comparison of Simple SingleItem Measures and the Common Toxicity Criteria in Detecting the Onset o

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A Comparison of Simple Single-Item Measures and
the Common Toxicity Criteria in Detecting the
Onset of Oxaliplatin-Induced Peripheral
Neuropathy in Patients with Colorectal Cancer
R. F. Morton, J. A. Sloan, A. Grothey, D. J.
Sargent, H. McLeod, E. M. Green, C. Fuchs, R. K.
Ramanathan, S. K. Williamson, R. M. Goldberg
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Background

• Peripheral neuropathy (PN) is common during
  treatment with Oxaliplatin
• Assessment of PN is historically done via the
  Common Toxicity Criteria (CTC)
• We developed a single-item numerical analogue
  scale assessment to help measure PN
• We compared the two measures to look at the
  sensitivity of the CTC in detecting the onset of
  PN

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Methods

• 696 patients randomized to FOLFOX4
• PN assesed bi-weekly during treatment
• NAS filled out at baseline and every 12 weeks
  during treatment

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NCCTG/Intergroup Trial N9741
IFL Irinotecan 5-FU/LV
RANDOMI ZAT ION
FOLFOX4 Oxaliplatin 5-FU/LV
IROX Irinotecan Oxaliplatin
Goldberg et al, JCO 2004
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NAS Tools
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An Empirical Anomaly

• According to CTC only 20 of patients experienced
  serious PN
• Clinical knowledge suggested the incidence rate
  should be much higher (about 80)

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Agreement
The agreement of lt 65 indicates CTC and NAS
measure different aspects of PN.
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Dose to 2 Point QOL Change
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Time to 2 Point QOL Change
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Which Comes First?
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Which Comes First?
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Conclusions

• Grade 2 PN is found to be a significant problem
  according to the NAS
• Using CTC, PN is under-reported
• NAS may allow for earlier detection
• NAS should be used in conjunction with CTC

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Abstract
Background Peripheral neuropathy (PN) is a
common and intrusive side effect of chemotherapy.
The assessment of PN is typically done via the
common toxicity criteria (CTC). To date there is
no optimal measure of peripheral neuropathy. We
developed simple single-item numerical analogue
scale (NAS) assessments for the unique
oxaliplatin-induced PN. The purpose of this
investigation was to asses the relative
sensitivity of the CTC and NAS measures in
detecting the onset and severity of PN in
patients receiving oxaliplatin.
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Abstract

• Methods
• 696 patients randomized to the FOLFOX4 arm of the
  practice-changing Intergroup/NCCTG study N9741
  provided data on the incidence and severity of PN
  experienced via
• bi-weekly CTC assessments and NAS measurements
  taken every 12 weeks. The NAS is a simple measure
  from 0 representing no PN to 10 representing PN
  as bad as it can be. A change of 2 points from
  baseline on the NAS was used as a conservative
  estimate of a clinically meaningful change in
  PN.

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Abstract
Results 276 patients (40) reported a 2 point
worsening from baseline in PN via NAS compared to
256 (37) with a CTC reported grade 2 PN and 99
(14) with a CTC reported grade 3 PN. For those
ultimately reporting PN, median dose to onset of
a clinically significant worsening of PN via NAS
was 424 mg/m2 relative to a dose to grade 2 (3)
PN of 765 (961) mg/m2 for CTC criteria. This
means that patients notice an increase in PN
about two or three months earlier via the NAS
relative to the CTC. Agreement between CTC grade
2 (3) PN and NAS assessment was only 65 (63)
with a Cohen's Kappa of 0.26 (0.13). The majority
of patients reported the 2 point decline in PN
via NAS prior to their reported CTC PN event (53
for grade 2, 83 for grade 3).
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Abstract

• Conclusions
• The CTC measurement of PN under-reports the
  incidence and time to onset of PN relative to
  simple single-item NAS measures. Grade 2 PN via
  the CTC is a clinically significant problem
  according to patient ratings on the NAS. In
  future studies, it is recommended that the CTC be
  supplemented by patient-reported measures of PN.