Greg Yothers, Stephanie R. Land, Clifford Y. Ko, D. Lawrence Wickerham, Louis Fehrenbacher, Jeffrey K. Giguere, Norman 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 Background

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. Methods

Patient Characteristics Characteristic Category FULV (N=136) (%) FLOX (N=151) (%) P- Value* Median time to LTS-01 Interview (Years) Year C-07 Entry Stage II III Gender Female Male Race White Black Asian/Pacific Isle Other/Unknown Age at Interview < ≥ * Wilcoxon, Chi Square, or Fisher’s Exact test Characteristic Category FULV (N=136) (%) FLOX (N=151) (%) P- Value* Marital Stat Married Not Married Education < College Grad College Grad Other/Unk Dis. Status Disease-free Colon Recur nd Primary C07 NTX Sbstdy Baseline Data Available 18 mos

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 < ), 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.Results

NTX-12 Score at LTS-01 Interview NTX12 Score Percent of Patients FULVFLOXDelta N Median462 p=0.046 Mean Wilcoxon rank-sum test

Change in NTX-12 Score at LTS-01 Interview NTX-12 Score, Change from Baseline Score Percent of Patients Wilcoxon signed-rank test NTX-12 Score, Change from 18 Month Score Percent of Patients Wilcoxon rank-sum test FULVFLOXDelta N Median440 p=0.90 Mean FULVFLOXDelta N33363 Median2 p<0.010 p=0.52 Mean

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 shape of 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 ← Favors FLOX → Favors FULV Individual 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. Acknowledgements

ASCO Saturday May 31, 2008 Patient and Survivor Care Poster Session Poster 39H, Abstract 9575