Association Between ABCC2 -24C>T and Nab-Paclitaxel-induced Peripheral Neuropathy in Japanese Patients With Pancreatic Cancer

Nab-paclitaxel is used to treat patients with pancreatic cancer. However, it frequently induces peripheral neuropathy. Notably, pharmacokinetic factors may be associated with neuropathic symptoms as the onset depends on the cumulative dose. Therefore, we prospectively examined the association betwee...

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Bibliographic Details
Published in:	Anticancer research Vol. 44; no. 11; p. 5023
Main Authors:	Nakayama, Hana, Ishida, Hiroo, Iidaka, Masanori, Kato, Shoko, Nakatani, Kei, Nakayama, Akihiro, Noguchi, Toshihiro, Nishihara, Shigetoshi, Oikawa, Shu, Usami, Tomono, Mitsui, Yuta, Ishii, Y U, Toshima, Hirokazu, Kobayashi, Kouji, Murase, Remi, Matsumoto, Natsumi, Suzuki, Kosuke, Shimada, Ken, Yoshida, Hitoshi, Fujita, Ken-Ichi
Format:	Journal Article
Language:	English
Published:	Greece 01-11-2024
Subjects:	Adult Aged Aged, 80 and over Albumins - administration & dosage Albumins - adverse effects Asian People - genetics East Asian People Female Humans Japan - epidemiology Male Middle Aged Multidrug Resistance-Associated Protein 2 Multidrug Resistance-Associated Proteins - genetics Paclitaxel - administration & dosage Paclitaxel - adverse effects Pancreatic Neoplasms - drug therapy Pancreatic Neoplasms - genetics Peripheral Nervous System Diseases - chemically induced Peripheral Nervous System Diseases - genetics Polymorphism, Single Nucleotide Prospective Studies Japan nab-paclitaxel time of onset ABCC2 genetic polymorphism peripheral neuropathy
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Summary:	Nab-paclitaxel is used to treat patients with pancreatic cancer. However, it frequently induces peripheral neuropathy. Notably, pharmacokinetic factors may be associated with neuropathic symptoms as the onset depends on the cumulative dose. Therefore, we prospectively examined the association between the cumulative dose of nab-paclitaxel at the onset of peripheral neuropathy and polymorphisms of hepatic transporter genes. Patients with pancreatic cancer receiving nab-paclitaxel (125 mg/m ) and gemcitabine (1,000 mg/m ) were enrolled. Peripheral neuropathy was assessed using the Common Terminology Criteria for Adverse Events (CTCAE), Patient-Reported Outcomes CTCAE (PRO-CTCAE), and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), every 2-12 weeks, and every 4 weeks thereafter. solute carrier organic anion transporter family member 1B1 (SLCO1B1) 521T>C, 388A>G; SLCO1B3 rs11045585; ATP-binding cassette transporters, subfamily B, member 1 (ABCB1) 1236C>T, 2677G>T/A, 3435C>T; ABCC1 rs2644983; ABCC2 24C>T; and ABCG2 421C>A were analyzed by direct sequencing. Correlations between transporter genotypes and cumulative dose at symptom onset were assessed using Kaplan-Meier and log-rank tests. In total, 25 patients were enrolled. The lowest median cumulative dose for nab-paclitaxel at peripheral neuropathy onset using PRO-CTCAE was 593 mg. By CTCAE it was 800 mg, and by FACT/GOG-Ntx it was 1,090 mg (p<0.0001). At symptom onset, patients with ABCC2 -24C/T genotype had received a significantly lower median cumulative dose by PRO-CTCAE (540 mg) than those with C/C (720 mg) (p=0.0188). However, the other polymorphisms studied were not associated with symptoms. Herein, we found for the first time that ABCC2 -24C/T genotype was significantly associated with the onset of nab-paclitaxel-induced peripheral neuropathy detected with PRO-CTCAE.
ISSN:	1791-7530
DOI:	10.21873/anticanres.17326