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Predicting Acute and Persistent Neuropathy Associated With Oxaliplatin

Alejandro, Linh M., PharmD*; Behrendt, Carolyn E., PhD; Chen, Kim, PharmD*; Openshaw, Harry, MD; Shibata, Stephen, MD§

American Journal of Clinical Oncology: August 2013 - Volume 36 - Issue 4 - p 331–337
doi: 10.1097/COC.0b013e318246b50d
Original Articles: Normal Tissue Effects
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Objectives: We sought to predict oxaliplatin-associated peripheral neuropathy during modified FOLFOX6 (mFOLFOX6) therapy.

Methods: Equal numbers of male and female patients with previously untreated, primary or recurrent colorectal cancer were followed through a first course of mFOLFOX6 with 85 mg/m2 oxaliplatin every 2 weeks. Accounting for correlation among a subject’s cycle, logistic regression estimated per cycle risk of acute (under 14 d) and persistent (14 d or more) neuropathy. Proportional hazards regression predicted time to persistent neuropathy.

Results: Among mFOLFOX6 recipients (n=50, age 58.9±10.1 y), 36% received concomitant bevacizumab. Of the total number of cycles, 94.2% (422/448) were evaluable. Most (84%) subjects reported neuropathy at least once; 74% reported acute and 48% reported persistent symptoms. On multivariate analysis, risk factors shared by acute and persistent neuropathy were body surface area >2.0, acute neuropathy in a past cycle, and lower body weight. In addition, risk of acute neuropathy decreased with age (adjusted for renal function and winter season), whereas risk of persistent neuropathy increased with cumulative dose of oxaliplatin and persistent neuropathy in a past cycle. Concomitant bevacizumab was not a risk factor when administered in stage IV disease but was associated with persistent neuropathy when administered experimentally in stage III. Females had no increased risk of either form of neuropathy. After 3 cycles, weight, body surface area, and prior acute neuropathy predicted time to persistent neuropathy.

Conclusions: Routinely available clinical factors predict acute and persistent neuropathy associated with oxaliplatin. When validated, the proposed prognostic score for persistent neuropathy can help clinicians counsel patients about chemotherapy.

Departments of *Pharmacy

Biostatistics

Neurology

§Medical Oncology, City of Hope National Medical Center, Duarte, CA

L.N., C.E.B. contributed equally to the design, conduct, and reporting of the study.

Present address: Linh M. Alejandro, PharmD, Department of Pharmacy, San Diego Cancer Center, UC San Diego Health System, Encinitas, CA.

The authors declare no conflicts of interest.

Presented at the Hematology/Oncology Pharmacy Association Conference, New Orleans, LA, March 24-27, 2010.

Reprints: Linh M. Alejandro, PharmD, Department of Pharmacy, San Diego Cancer Center, UC San Diego Health System, 1200 Garden View Road, Suite 200, Encinitas, CA 92094. E-mail: lalejandro@ucsd.edu.

© 2013 by Lippincott Williams & Wilkins, Inc