2011/7/29

Validation of self-reported questionnaire (PNQ) inneurotoxicity of oxaliplatin with comparing
physician's and patient's assessments:CSP-HOR 16
Katsunori Shinozaki5),
Toraji Amano1)2), Yasuhiro Shimada3), Tomohiro Nishina4),
Taito Esaki6),
Yoshito Komatsu7), Akihito Tsuji8),
Yasushi Tsuji9),
Kenji Amagai10), Taro Sato11),
Keiichiro Ishibashi12),
Kojiro Shimozuma13),
Hirotoshi Akita1), Yasuo Ohashi2)14), Frederick H. Hausheer15)
1 ) Dept. of Medical Oncology, Hokkaido University, Graduate School of Medicine
2 ) Public Health Research Foundation3 ) Dept. of Gastrointestinal Oncology, National Cancer Center Hospital4 ) Dept. of Gastroenterology, Shikoku Cancer Center5 ) Dept. of Clinical Oncology, Hiroshima Prefectural Hospital6 ) Gastrointestinal and Medical Oncology Division, National Kyushu Cancer Center7 ) Dept. of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center8 ) Medical Oncology, Kochi Health Sciences Center9 ) Dept. of Medical Oncology, Tonan Hospital10) Dept. of Gastroenterology, Ibaraki Prefectural Central Hospital11) Dept. of Medical Oncology, Kinki University, Faculty of Medicine
12) Dept. of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University
13) Lab. of Health Services Res., Dpt. of Biomedical Sciences, College of Life Sciences, Ritsumeikan Univ.
14) Dept. of Biostatistics, School of Public Health, Graduate School of Medicine, University of Tokyo
15) BioNumerik Pharmaceuticals, Inc,JSMO Jul. 21, 2011

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研究費の財源□受託 ■寄付 □科学研究費 □その他（発表者氏名

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財団法人パブリックヘルスリサーチセンター

北海道大学病院 腫瘍内科/医 員

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島田安博
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国立がん研究センター中央病院 消化管内科

該当有りの場合：企業名等

1

2011/7/29

BACKGROUND● Oxaliplatin-containing regimens is standard

chemotherapy for colorectal cancer patients.

● Neurotoxicity is the most common adverse

event .

● There are two types of the toxicity, acute andchronic. Chronic neurotoxicity is dose-dependentand persistent, known as dose-limiting toxicity.
JSMO Jul. 21, 2011

BACKGROUND● Common Terminology Criteria for Adverse Events (CTCAE)

is generally used to evaluate the degree of neurotoxicity.

● Physician's evaluation with CTCAE is subjective, and it has

a tendency toward down grading.

● Patient-reported outcomes are important tools forevaluating adverse effects.

● Patient Neurotoxicity Questionnaire (PNQ) for theneurotoxicity of oxaliplatin is a self-reported and simple
questionnaire with only two items.
JSMO Jul. 21, 2011

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2011/7/29

OBJECTIVESThis study prospectively investigates the chronic
neurotoxicity of oxaliplatin with physician-based CTCAE
grading and self-reported questionnaires.
Instruments evaluated● CTCAE : Common Terminology Criteria for Adverse Events v3.0
● FACT/GOG-Ntx: Ntx-subscale : Functional Assessment ofCancer Therapy / Gynecologic Oncology Group Neurotoxicity questionnaire● PNQ : Patient Neurotoxicity Questionnaire for theneurotoxicity of oxaliplatin

JSMO Jul. 21, 2011

PNQ-oxaliplatin

JSMO Jul. 21, 2011

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2011/7/29

PATIENTS AND MAIN ELIGIBILITY CRITERIA● Patients (pts)120 pts enrolled in 10 centers （Jan.2008 – Oct.2009)● Main Eligibility Criteria* Performance Status ( ECOG ) : 0, 1
* Age : 20 – 75* Pathologically confirmed colorectal adenocarcinoma* To be treated with FOLFOX4 or modified FOLFOX6* Oxaliplatin naive
JSMO Jul. 21, 2011

ASSESSMENT METHODS
Neurotoxicity Assessments
Baseline

Every 2 cycle

Every 8 weeks

FOLFOX4 or modified FOLFOX6Baseline
QOL Assessments

3rd Assessment

5th Assessment

Test-Retest
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EVALUATION METHODS
Evaluation properties● Compliance of the instruments● Criterion validity: Correlation of the PNQ with the other instruments● Reproducibility : Test-Retest correlation● Clinical validity : Change of the scores over time
● Frequency and severity of neurotoxicity● Cumlative oxaliplatin dose and neurotoxicity
JSMO 2011/07/21

RESULTS

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2011/7/29

PATIENTS CHARACTERISTICS
Variables

N=113

(%)
( 57.5 )( 39.8 )( 2.6 )

Sex

Male
FemaleUnknown

65
453AgeMedian ( range )62 ( 34 – 74 )

PS

0
12-4
Unknown

921605

No. disease site

Median ( range )2(0-6)

Disease status

Primary
Recurrence
Unknown

5160
2( 81.4 )( 14.2 )( 0.0 )
( 4.4 )
( 45.1 )( 53.1 )( 1.8 )
JSMO Jul. 21, 2011

PATIENTS CHARACTERISTICS
Variables
Prior Surgery

RadicalNon-radical
Unknown

Prior Radiation

N=113(%)

52
264( 46.0 )( 23.0 )( 3.5 )

4( 3.5 )PriorChemotherapy

FU - containing
others52
7( 46.0 )( 6.2 )

Treatment line

12Unknown

7725
11( 68.1 )( 22.1 )( 9.7)

Assessment
pointsMedian ( range )5.4 ( 1- 13)

Cumlative
dose/cycle

Median( range )1148 mg / 9.7 cycle( 140 – 2240 / 1 – 25 )JSMO Jul. 21, 2011

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2011/7/29

PHYSICIAN & PATIENT COMPLIANCE
Baseline

3rdAssessment

5thAssessment( Post 4 cycles ) ( Post 8 cycles )No. of patients

11310873

PNQ

97.3

94.0

95.9

Ntx

95.6

90.7

97.3

CTCAE

98.2

97.7

97.9

ResponseRate (%)

JSMO 2011/07/21

CORRELATION BETWEEN THE INSTRUMENT
Sensory
Component

PNQ

CTCAE

Ntx-subscale

PNQ

1.0--

CTCAE

0.596

1.0-

Ntx-subscale

0.597

0.522

1.0

Spearman's correlation coefficient : Overall Assessment
JSMO 2011/07/21

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CORRELATION BETWEEN THE INSTRUMENT
MotorComponent

PNQCTCAE

Ntx-subscale

PNQ

1.0--CTCAE

0.391

1.0-

Ntx-subscale

0.445

0.294

1.0

Spearman's correlation coefficient : Overall Assessment
JSMO 2011/07/21

REPRODUCIBILITY ( PNQ & Ntx )N = 72

Test-Retest
Correlation Coefficient

Sensory-Component

0.808

Motor-Component

0.589

Ntx-subscale

0.583

Spearman's correlation coefficient :All Cases
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FREQUENCY AND SEVERITY
Percentage ( % )Grade 2 <Baseline
JSMO 2011/07/21

Mean Score ( Max 4 )CHANGE OF THE SCORES

Baseline

JSMO 2011/07/21

92011/7/29

CUMLATIVE DOSE AND NEUROTOXICITY

Cumulative Probability

Sensory
Component

Grade 1 <Grade 2 <N=97
Oxaliplatin Cumulative Dose ( mg/㎡ )

PNQ
CTCAE
JSMO 2011/07/21

CUMLATIVE DOSE AND NEUROTOXICITY
N=97

Cumulative Probability

Motor
Component

PNQ
CTCAE
Grade 1<

Grade 2<

Oxaliplatin Cumulative Dose ( mg/㎡ )JSMO 2011/07/21

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CONCLUSIONS● PNQ shows high response rate similar to CTCAE.
● Sensory component of PNQ shows moderatecorrelation, but Motor component shows weekcorrelation with the others.
●Reproducibility of PNQ is higher in Sensory than Motor
component.
●In this study, oxaliplatin neurotoxicity has worse dose
dependent tendency.
●In Motor component, patient-based PNQ shows worse
neurotoxicity than physician-based CTCAE.
JSMO 2011/07/21

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