Long-term administration and efficacy of oxaliplatin with no neurotoxicity in a patient with rectal cancer: Association between neurotoxicity and the GSTP1 polymorphism.
Neurotoxicity is one of the most frequent side-effects of oxaliplatin. Oxaliplatin-induced cumulative and dose-limiting neurotoxicity either results in dose reduction or decreases the patients' quality of life. However, the symptoms of neurotoxicity often vary among patients. The current study presents the case of a male with rectal cancer, who was administered a cumulative oxaliplatin dose of >5,000 mg/m2without developing neurotoxicity or allergic reactions. Consequently, this patient continued therapy with modified 5-fluorouracil, leucovorin and oxaliplatin treatment for four years, with stabilization of the disease. This case indicates that if oxaliplatin-containing chemotherapy shows efficacy with no toxicity, the long-term administration of oxaliplatin would be effective and tolerable. Previously, the analysis of genomic polymorphisms in drug target genes has been important for explaining interindividual variations in the efficacy and toxicity of anti-cancer drugs. In the present patient, the glutathione S-transferase P1 (GSTP1) gene polymorphism, which is involved in the detoxification of platinum drugs, was analyzed. The genotype of the present case has been revealed as wild type (Ile/Ile) genotype. In addition, the associations between oxaliplatin-induced neurotoxicity and the GSTP1 polymorphism were also assessed. Certain studies have demonstrated that oxaliplatin-induced neurotoxicity occurs more frequently in patients with the Ile/Ile genotype, while others have demonstrated that those patients with the Val/Val or Ile/Val genotypes are more likely to develop neurotoxicity. Therefore, correlation between the GSTP1 polymorphism and oxaliplatin-induced neurotoxicity remains controversial. Overall, further development of individualized chemotherapy with an analysis of genomic polymorphisms in the drug target genes is required for the prophylaxis oxaliplatin-induced neurotoxicity.
Department of Pharmacy, Houju Memorial Hospital, Nomi, Ishikawa 923-1226, Japan.
Hironori
H
Kitade
Outpatient Cancer Chemotherapy Center, Houju Memorial Hospital, Nomi, Ishikawa 923-1226, Japan ; Medicalm Research Institute, Kanazawa Medical University, Kahoku, Ishikawa 920-0293, Japan.
Takeo
T
Shimasaki
Department of Radiology, Houju Memorial Hospital, Nomi, Ishikawa 923-1226, Japan.
Saya
S
Igarashi
Department of Surgery, Houju Memorial Hospital, Nomi, Ishikawa 923-1226, Japan.
Hiroshi
H
Sakuma
Department of Pharmacy, Houju Memorial Hospital, Nomi, Ishikawa 923-1226, Japan.
Mitsue
M
Mori
Medicalm Research Institute, Kanazawa Medical University, Kahoku, Ishikawa 920-0293, Japan.
Naohisa
N
Tomosugi
Department of Surgery, Houju Memorial Hospital, Nomi, Ishikawa 923-1226, Japan.
Masuo
M
Nakai
GSTP1; colorectal cancer; neurotoxicity; oxaliplatin