title: A case of metastatic renal cell carcinoma and bile duct carcinoma treated with a combination of sunitinib and gemcitabine.
abstract: BACKGROUND
  Metastatic renal cell carcinoma (mRCC) had been a chemo-refractory disease, but recent advances in multiple kinase inhibitors such as sunitinib have dramatically changed the clinical course of mRCC. Sunitinib is used for mRCC chemotherapy based on the favorable results of a recent clinical trial, but specific biomarkers predicting efficacy and safety are not yet available. Locally advanced bile duct carcinoma (BDC) has generally been treated with single agent gemcitabine or as doublet therapy with cisplatin. Concomitant occurrence of mRCC and BDC is extremely rare, and a standard therapeutic strategy has not been established.
  
  
  METHODS
  A 65-year-old woman was diagnosed as having multiple mRCC and intercurrent, locally advanced BDC. A single course of combination therapy with sunitinib (25 mg/day, day2-15) and gemcitabine (750 mg/m(2), days 1, 8) was administered, and this showed obvious effects, with partial response for mRCC and stable disease for BDC. However, the patient also experienced severe adverse events, including hematological and various non-hematological toxicities; the combination therapy was then terminated on day 13 after its initiation. She recovered on day 28 and is alive 3.5 years after the diagnosis. The plasma trough levels of sunitinib and its active metabolite SU12662 on day 13 were 91.5 ng/mL and 19.2 ng/mL, respectively, which were relatively higher than in previous reports. Analysis of her single nucleotide polymorphisms (SNPs) detected TC in ABCB1 3435C/T, TC in 1236C/T and TT in 2677G/T, suggesting a possible TTT haplotype.
  
  
  CONCLUSIONS
  A rare case of double cancer of mRCC and BDC was treated by combination chemotherapy. Although unknown synergistic mechanisms of these agents may be involved, severe toxicities might be possibly associated with high sunitinib exposure. Further exploration of combination therapy with sunitinib and gemcitabine is required.
authors.affiliation: Department of Medical Oncology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyouhama, Chuo-ku, Fukuoka, 810-8563, Japan. t-kotoe@kyumed.jp.
authors.forename: Kotoe
authors.initials: K
authors.lastname: Takayoshi
authors.affiliation: Department of Medical Oncology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyouhama, Chuo-ku, Fukuoka, 810-8563, Japan. me_llamo_kosuke_sagara@yahoo.co.jp.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Sagara
authors.affiliation: Department of Medical Oncology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyouhama, Chuo-ku, Fukuoka, 810-8563, Japan. keitauch@kyumed.jp.
authors.forename: Keita
authors.initials: K
authors.lastname: Uchino
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan. hkusaba@intmed1.med.kyushu-u.ac.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kusaba
authors.affiliation: Department of Urology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan. sakamo@kyumed.jp.
authors.forename: Naotaka
authors.initials: N
authors.lastname: Sakamoto
authors.affiliation: Department of Urology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan. iguchi@miyakonojo.hosp.go.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Iguchi
authors.affiliation: Department of Comprehensive Clinical Oncology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan. e-baba@c-oncology.med.kyushu-u.ac.jp.
authors.forename: Eishi
authors.initials: E
authors.lastname: Baba
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001650:Bile Duct Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000188:drug therapy*; D049448:Cholangiopancreatography, Magnetic Resonance; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000493:pharmacokinetics; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000556:secondary; D009362:Neoplasm Metastasis; D016609:Neoplasms, Second Primary / Q000175:diagnosis / Q000188:drug therapy*; D020641:Polymorphism, Single Nucleotide; D011758:Pyrroles / Q000008:administration & dosage / Q000493:pharmacokinetics; D000077210:Sunitinib; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D007211:Indoles; D011758:Pyrroles; D003841:Deoxycytidine; D000077210:Sunitinib; D000093542:Gemcitabine