Effect of renal function on pemetrexed-induced haematotoxicity.
Pemetrexed (PEM) is an anticancer agent used for the treatment of non-small cell lung cancer, malignant pleural mesothelioma and thymoma. Reportedly, PEM has higher efficacy and safety when used in combination with platinum-based agents. However, there are only few reports on the safety of PEM in patients with an eGFR of ≤45 mL/min. We examined the effect of renal function on the safety of regimens containing PEM.



We retrospectively reviewed 221 patients with lung cancer, malignant pleural mesothelioma or thymoma who received treatment with a PEM-containing regimen between 2009 and 2014. Subgroup analyses were performed on the basis of pre-treatment renal function: group A [creatinine clearance (CLcr), <45 mL/min]; group B (CLcr, 45-80 mL/min); and group C (CLcr, ≥80 mL/min). For the purpose of this analysis, the lowest documented blood cell counts and haemoglobin levels, the highest levels of serum creatinine, aspartate aminotransferase, alanine aminotransferase and CLcr from the time of initial administration up to prior to the start of second administration were considered.



Groups A, B and C had 8, 123 and 90 patients, respectively. The incidence of grade 2 thrombocytopaenia was significantly higher in group A as compared to that in groups B (P < 0.01) and C (P < 0.05). On multivariate analysis, only a CLcr of <45 mL/min was an independent risk factor for thrombocytopaenia of ≥grade 2.



When administering a PEM-containing regimen, thrombocytopaenia of ≥grade 2 is more likely to develop in patients with a CLcr of <45 mL/min.
Department of Clinical Pharmacy, School of Medicine, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan.
Yosuke
Y
Ando
Department of Clinical Pharmacy, School of Medicine, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan. taka-h@fujita-hu.ac.jp.
Takahiro
T
Hayashi
College of Pharmacy, Kinjo Gakuin University, 2-1723 Omori, Moriyama, Nagoya, 463-8521, Japan.
Moeko
M
Ujita
College of Pharmacy, Kinjo Gakuin University, 2-1723 Omori, Moriyama, Nagoya, 463-8521, Japan.
Sumie
S
Murai
Department of Clinical Pharmacy, School of Medicine, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan.
Hideki
H
Ohta
Department of Hematology, School of Medicine, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan.
Kaori
K
Ito
Department of Respiratory Medicine, School of Medicine, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan.
Teppei
T
Yamaguchi
College of Pharmacy, Kinjo Gakuin University, 2-1723 Omori, Moriyama, Nagoya, 463-8521, Japan.
Minori
M
Funatsu
College of Pharmacy, Kinjo Gakuin University, 2-1723 Omori, Moriyama, Nagoya, 463-8521, Japan.
Yoshiaki
Y
Ikeda
Department of Respiratory Medicine, School of Medicine, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan.
Kazuyoshi
K
Imaizumi
Department of Medical Oncology, School of Medicine, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan.
Kenji
K
Kawada
College of Pharmacy, Kinjo Gakuin University, 2-1723 Omori, Moriyama, Nagoya, 463-8521, Japan.
Kimio
K
Yasuda
Department of Clinical Pharmacy, School of Medicine, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan.
Shigeki
S
Yamada
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D003404:Creatinine / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D015994:Incidence; D007677:Kidney Function Tests; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D015999:Multivariate Analysis; D000068437:Pemetrexed / Q000008:administration & dosage / Q000009:adverse effects*; D010997:Pleural Neoplasms / Q000188:drug therapy; D012189:Retrospective Studies; D012307:Risk Factors; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000453:epidemiology; D013945:Thymoma / Q000188:drug therapy
D000068437:Pemetrexed; D003404:Creatinine
Malignant pleural mesothelioma; Non-small cell lung cancer; Pemetrexed; Renal dysfunction; Thrombocytopaenia