Greg Yothers, Stephanie R. Land, Greg Yothers, Stephanie R. Land, Clifford Y. Ko, D. Lawrence Wickerham, Clifford Y. Ko, D. Lawrence Wickerham, Louis Fehrenbacher, Jeffrey K. Giguere,Louis Fehrenbacher, Jeffrey K. Giguere,Norman Wolmark, and Patricia A. GanzNorman Wolmark, and Patricia A. Ganz

Neurotoxicity is an important acute toxicity associated with oxaliplatin therapy, yet little is known about neurotoxicity in long term colon cancer survivors treated with oxaliplatin as part of adjuvant therapy. NSABP LTS-01 is a comprehensive study examining patient reported outcomes in long term survivors of colon and rectal cancer previously treated on NSABP adjuvant trials. We report preliminary neurotoxicity patient reported outcomes results from LTS-01 for patients accrued to C-07 from 2000-2002.

BackgroundBackground

Eligible patients from NSABP Protocol C-07 were recruited and consented by NSABP investigators providing regular follow-up. After consent, telephone interviews were used to collect patient reported outcomes including neurotoxicity by the validated FACT/GOG Oxaliplatin-Specific neurotoxicity questionnaire (NTX-12). A subset of patients completed the NTX-12 as part of the original C-07 trial. Patients were analyzed according to their randomly assigned treatment in the earlier C-07 trial. Statistical comparisons of neurotoxicity across treatments used the Wilcoxon test.

MethodsMethods

Patient CharacteristicsPatient CharacteristicsCharacteristic

CategoryFULV

(N=136) (%)FLOX

(N=151) (%)P-

Value*

Median time to LTS-01 Interview (Years) 5.8 5.9 0.08

Year C-07 Entry 2000 23.5 34.4

2001 33.8 30.5 0.12

2002 42.7 35.1

Stage II 37.5 29.80.17

III 62.5 70.2

Gender Female 33.8 41.7 0.18

Male 66.2 58.3

Race White 92.6 91.4

0.69 Black 3.7 2.7

Asian/Pacific Isle 1.5 1.3

Other/Unknown 2.2 4.6

Age at Interview < 50 11.8 7.3

50-59 24.3 27.8

60-69 36.8 35.1 0.72

70-79 23.5 25.8

≥ 80 3.7 4.0

* Wilcoxon, Chi Square, or Fisher’s Exact test

CharacteristicCategory

FULV(N=136) (%)

FLOX(N=151) (%)

P-Value*

Marital Stat Married 76.5 75.5 0.98

Not Married 23.5 24.5

Education < College Grad 52.9 55.6

College Grad + 45.6 42.4 0.83

Other/Unk 1.5 2.0

Dis. Status Disease-free 86.8 87.4

Colon Recur 8.1 8.6 0.89

2nd Primary 5.2 4.0

C07 NTX Sbstdy Baseline 25.7 29.8 0.51

Data Available 18 mos. 24.3 23.8 1.00

•LTS-01 opened in October 2006 and, as of March 2008, neurotoxicity (NT) patient reported outcomes data are available from 287 pts (53% on FLOX). •Characteristics were similar across treatments with 50% of pts over age 65, 92% white, 8% with CC recurrence, and 5% with new primary cancer. •Median time from C-07 randomization to LTS-01 interview was 6 years. •FLOX pts had more NT than FULV pts (p = 0.046), but the mean difference in NTX-12 score was 1.4, less than the 4 points considered clinically important. •Individual item scores with significantly more NT on FLOX were: trouble buttoning buttons (8 v 17% with any severity, p = 0.033), numbness/tingling in feet (22 v 44%, p < 0.0001), and pain in hands/feet when exposed to cold (26 v 42%, p = 0.006). •In the subset of 80 pts with baseline (BL) NTX-12 data (56% FLOX), the change from BL score was similar for both treatments. •In a subset of 36 FLOX pts with 18- month data, NT was similar at 18 months and the LTS assessment at 5-7 years.

ResultsResults

NTX-12 Score at LTS-01 InterviewNTX-12 Score at LTS-01 Interview

0

5

10

15

20

25

30

FULVFLOX

NTX12 Score

Per

cen

t of

Pat

ien

ts

FULV FLOX Delta

N 136 151 15

Median 4 6 2 p=0.046

Mean 6.0 7.4 1.4

Wilcoxon rank-sum test

0

10

20

30

40

50

60

Drop 11+ Drop 4-10 0 +/- 3 Incr 4-10 Incr 11+

FULVFLOX

Change in NTX-12 Score at LTS-01 InterviewChange in NTX-12 Score at LTS-01 Interview

0

10

20

30

40

50

Drop 4-5 0 +/- 3 Incr 4-10 Incr 11+

FULVFLOX

NTX-12 Score, Change from Baseline Score

Per

cen

t of

Pat

ien

ts

Wilcoxon signed-rank test

NTX-12 Score, Change from 18 Month Score

Per

cen

t of

Pat

ien

ts

Wilcoxon rank-sum test

FULV FLOX Delta

N 35 45 10

Median 4 4 0 p=0.90

Mean 5.0 4.6 -0.4

FULV FLOX Delta

N 33 36 3

Median 2 p<0.01 0 p=0.5 2

Mean 3.6 1.0 -2.6

0.5 1 1.5 2 2.5

Relative Risk of Symptom (95% Conf. Int.)Joint pain or muscle cramps

Weak all over

Trouble hearing

Discomfort in hands

Ringing or buzzing in ears

Discomfort in feet

Trouble feeling shapeof small objects in hand

Numbness or tingling in hands

Pain in hands/feet with cold temps

Numbness or tingling in feet

Trouble buttoning buttons

Trouble walking

←FavorsFLOX

→FavorsFULV

Individual symptoms from NTX-12 ScaleIndividual symptoms from NTX-12 Scale

This work is supported by grants from the National Cancer Institute and the American Cancer Society. We wish to thank the membership of the NSABP, the staff of the NSABP Biostatistical and Operations Centers and the Jonsson Comprehensive Cancer Center at UCLA, and especially the trial participants without whom this research would not have been possible.

AcknowledgementsAcknowledgements

ASCO Saturday May 31, 2008Patient and Survivor Care Poster Session

Poster 39H, Abstract 9575