A case of metastatic renal cell carcinoma and bile duct carcinoma treated with a combination of sunitinib and gemcitabine

BMC Cancer, May 2015

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. Case presentation 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/m2, 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. Conclusion 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.

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A case of metastatic renal cell carcinoma and bile duct carcinoma treated with a combination of sunitinib and gemcitabine

Takayoshi et al. BMC Cancer A case of metastatic renal cell carcinoma and bile duct carcinoma treated with a combination of sunitinib and gemcitabine Kotoe Takayoshi 0 Kosuke Sagara 0 Keita Uchino 0 Hitoshi Kusaba Naotaka Sakamoto Atsushi Iguchi Eishi Baba 0 Department of Medical Oncology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center , 1-8-1 Jigyouhama, Chuo-ku, Fukuoka 810-8563 , Japan 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. Case presentation: 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/m2, 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. Conclusion: 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. ABCB1; Adverse event; Bile duct carcinoma; Gemcitabine; Plasma concentration; Renal cell carcinoma; Sunitinib - Background Renal cell carcinoma (RCC) is one of the most serious urological malignancies. mRCC is initially diagnosed in 30 % of RCC patients, and 2040 % of curatively operated RCC patients recur. Recently, new classes of molecular targeted agents, such as tyrosine kinase inhibitors and mTOR inhibitors, have become widely used for mRCC. Sunitinib is an oral tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR)-1, 2 and 3, platelet-derived growth factor receptor (PDGFR)- and -, RET, and c-Kit. It has often been used for mRCC chemotherapy based on the favorable results of a phase III clinical trial showing superiority over interferon alpha [1]. Recent studies, however, have reported some adverse events including fatigue, bone marrow suppression, hand-foot syndrome, stomatitis, hypertension and hypothyroidism [1]. In a pivotal study of sunitinib, 38 % of the patients in the sunitinib group required dose interruptions due to adverse events, and 32 % required dose reductions to continue treatment courses [1]. Identifying biomarkers that can predict the response and adverse events of sunitinib is urgently needed in order to obtain the optimal effects of this drug. Biliary tract cancer is rare in the Western countries, while it is relatively common in Latin America and Asia, including in Japan [2], and 5090 % of patients was diagnosed as having advanced cancer and had a poor prognosis [3]. Combination chemotherapy consisting of fluoropyrimidine and gemcitabine has been given not only for metastatic biliary tract cancer but also for locally advanced disease. A recent clinical study showed the efficacy of the combination of gemcitabine and platinum for metastatic biliary tract cancer [4, 5]. While adverse events of gemcitabine such as myelosuppression, liver dysfunction, general fatigue, alopecia, and nausea were often observed, they were mostly tolerable in the pivotal clinical studies. Concurrent occurrence of RCC and BDC is extremely rare. Only two cases have been reported in the literature, and the biological background of the synchronous primary malignancy was not clarified [6, 7]. Standard therapeutic strategies have generally not been established for cases of unresectable double primary cancers, and no chemotherapy was given to the above two cases. In the present case with concurrent mRCC and BDC, combination therapy of sunitinib and gemcitabine, which are both effective agents for each disease, was used, and both response and various adverse (...truncated)


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Kotoe Takayoshi, Kosuke Sagara, Keita Uchino, Hitoshi Kusaba, Naotaka Sakamoto, Atsushi Iguchi, Eishi Baba. A case of metastatic renal cell carcinoma and bile duct carcinoma treated with a combination of sunitinib and gemcitabine, BMC Cancer, 2015, pp. 426, 15, DOI: 10.1186/s12885-015-1443-2