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
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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)