Article:Efficacy and safety of everolimus treatment in a hemodialysis patient with metastatic atypical bronchial carcinoid: case report and literature review. (5861646)

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This page is the ScienceSource HTML version of the scholarly article described at Its title is Efficacy and safety of everolimus treatment in a hemodialysis patient with metastatic atypical bronchial carcinoid: case report and literature review. and the publication date was 2018-03-20. The initial author is M. P. Brizzi.

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Journal Information

Title: BMC Cancer

Efficacy and safety of everolimus treatment in a hemodialysis patient with metastatic atypical bronchial carcinoid: case report and literature review

  • M. P. Brizzi
  • A. La Salvia
  • M. Tampellini
  • C. Sonetto
  • M. Volante
  • G. V. Scagliotti

Publication date (epub): 3/2018

Publication date (pmc-release): 3/2018

Publication date (collection): /2018



Everolimus was recently approved for the treatment of neuroendocrine tumors. However, its efficacy and tolerability in hemodialysis patients with end-stage renal disease is not established.

Case presentation

We describe the case of a 47-year-old man with end-stage renal disease who received everolimus plus Lanreotide for 9 months for the management of metastatic atypical bronchial carcinoid.


Everolimus is a treatment option for hemodialysis patients with metastatic atypical bronchial carcinoid. Based on our case report and review of literature, Everolimus does not require any dose reductions and is overall well tolerated in hemodialysis patients.



In two phase III trials everolimus has been shown to be active against neuroendocrine tumors (NETs) arising from the lung [[1], [2]]. Its tolerability in lung NET patients with concomitant severe renal insufficiency has never been reported. Here we describe the case of a hemodialysis patient with metastatic atypical bronchial carcinoid treated with everolimus.

Case presentation

In February 2011, a 47-year-old white male patient underwent right lung lobectomy for resection of an atypical bronchial carcinoid (pT1pN2). His medical history was significant for end-stage renal disease (ESRD) secondary to focal segmental glomerulosclerosis requiring iterative hemodialysis. In September 2011 a right hepatectomy was performed due to liver metastases; metastatic disease progressed to liver and bone over the next 17 months. Monthly administration of intramuscular Lanreotide 120 mg was initiated and continued for 1 year. In March 2014 further disease progression was noted and oral everolimus was initiated at a dose of 10 mg/day, then reduced to 5 mg/day 1 month later due to persistent grade II mucositis. No grade III-IV toxicities occurred. A computed tomography (CT) scan taken 3 months later showed stabilization of disease. Everolimus therapy was discontinued in November 2014, after a 9-month course of treatment, because of hepatic and bone disease progression. Somatostatin analogue therapy was continued throughout. A CT scan taken 6 months later revealed progression of liver disease and development of peritoneal metastases, for which 5 cycles of chemotherapy with temozolomide were administered from April to August 2015. Liver metastases and peritoneal metastases progressed, and oral metronomic chemotherapy with capecitabine was initiated in November 2015. The patient died in January 2016 due to disease progression.

Discussion and conclusions

Several therapeutic options are available for front-line treatment of metastatic bronchial carcinoids, including somatostatin analogues, chemotherapy, and peptide receptor radionuclide therapy [[3]].

However, comorbidities such as renal failure can limit or even preclude such treatments [[4]].

Unfortunately, there are no established guidelines for the administration of chemotherapeutic or target agents in hemodialysis patients [[5]]. The prevalence of renal insufficiency in cancer patients is growing [[6]], making observations in any tumor setting important.

To the best of our knowledge, this is the first report of a hemodialysis patient with metastatic atypical bronchial carcinoid treated with everolimus. In the one case of a hemodialysis patient with metastatic ileal well differentiated NET (G1) described so far, disease stabilization was achieved without any adverse effects [[7]].

Clinical trials investigating everolimus activity have excluded ESRD patients because the condition is thought to alter drug pharmacokinetics. Indeed, drug clearance may be different in hemodialysis patients, increasing the risk of overdosage and higher toxicities [[8]], or it may be more rapid and thus reduce drug efficacy. Recent reports have documented that everolimus pharmacokinetics is not altered by hemodialysis in patients with metastatic renal cell cancer [[9][13]], probably owing to the absence of diffusion of everolimus through commonly used dialysis membranes and in the dialysate fluid (Table 1). Another explanation for the unchanged tolerability profile of everolimus in patients with renal insufficiency is that the drug is predominantly metabolized by the liver and eliminated in the bile [[14]].Table 1

Everolimus in the treatment of hemodialysis patients with metastatic renal cell carcinomas

Authors/reference Study description No. of patients included No. of prior regimen Everolimus dosage Best responses Duration of response Safety
Thiery-Vuillemin A et al. [[9]] Case reports 2 1; 1 5 mg NA NA Grade II asthenia, diarrhea and mucositis; grade III hyperglycemia
Syrios J et al. [[10]] Case reports 2 1; 1 10 mg SD; CR 4 mo; 40 mo Well tolerated
Adytia V et al. [[11]] Single institution experience 6 NA 10 mg; 1 dosage reduction to 5 mg SD Median duration of therapy 1.9 mo (0.4–17) 5 patients: well tolerated, 1 patient: pneumonitis
Czarnecka AM et al. [[12]] Single institution experience 1 2 10 mg PD 4 mo Well tolerated
Omae K et al. [[13]] Single institution experience 4 1 SD Median duration of therapy 6.7 mo Grade II rash, diarrhea, pneumonitis, and mucositis

Abbreviations: NA Not available, SD Stable disease, PD Progression of disease, mo Months

Moreover, repeated surgery for multiple renal cell carcinoma in patients with von Hippel-Lindau syndrome may lead to ESRD in up to 25% of cases [[15]]. In these young patients, pancreatic NETs occurrence is frequent. Treatment with everolimus may be considered safe in this patient setting. Everolimus therapy is feasible in hemodialysis patients with metastatic bronchial carcinoid. Its observed efficacy and tolerability profile are similar to those reported in patients with normal renal function. To confirm the clinical features of everolimus in NET patients undergoing hemodialysis, data collection from single case or case series is highly envisioned. This will remove any concern about treating this rare patient subgroup with an active treatment allowing their inclusion in prospective trials.





This research did not receive any specific grant from funding agencies in the public, commercial, or not for-profit sectors.

Availability of data and materials

The data used and/or analyzed during the current study are available from the corresponding author on reasonable request.


  1. JC YaoN FazioS SinghR BuzzoniC CarnaghiE WolinEverolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. RAD001 in advanced neuroendocrine Tumours, fourth trial (RADIANT-4) study groupLancet20163871002296897710.1016/S0140-6736(15)00817-X26703889
  2. N FazioD GranbergA GrossmanS SaletanJ KlimovskyA PanneerselvamEverolimus plus octreotide long-acting repeatable in patients with advanced lung neuroendocrine tumors: analysis of the phase 3, randomized, placebo-controlled RADIANT-2 studyChest2013143495596210.1378/chest.12-110823187897
  3. ME CaplinE BaudinP FerollaP FilossoM Garcia-YusteE LimENETS consensus conference participants. Pulmonary neuroendocrine (carcinoid) tumors: European neuroendocrine tumor society expert consensus and recommendations for best practice for typical and atypical pulmonary carcinoidsAnn Oncol20152681604162010.1093/annonc/mdv04125646366
  4. FJ MaoBI RiniThe ineligible patient: how to treat patients not included in clinical studiesWorld J Urol201432191810.1007/s00345-013-1042-223436165
  5. V Launay-VacherS OudardN JanusJ GligorovX PourratO RixePrevalence of renal insufficiency in cancer patients and implications for anticancer drug management: the renal insufficiency and anticancer medications (IRMA) studyCancer20071061376138410.1002/cncr.22904
  6. K CengisIncreased incidence of neoplasia in chronic renal failureInt Urol Nephrol200233112112610.1023/A:101448991115312090317
  7. JM Van RooijenEG De VriesHemodialysis no reason to withhold everolimusCancer Chemother Pharmacol201371127327410.1007/s00280-012-2021-923135528
  8. N JanusJ ThariatH BoulangerG DerayV Launay-VacherProposal for dosage adjustment and timing of chemotherapy in hemodialyzed patientsAnn Oncol20102171395140310.1093/annonc/mdp59820118214
  9. A Thiery-VuilleminE CurtitT MaurinaD MontangeC SucciT NguyenHemodialysis does not affect everolimus pharmacokinetics: two cases of patients with metastatic renal cell cancerAnn Oncol201223112992299310.1093/annonc/mds47723071263
  10. J SyriosG KechagiasN TsavarisTreatment of patients with metastatic renal cell carcinoma undergoing hemodialysis: case report of two patients and short literature reviewBMC Nephrol2013148410.1186/1471-2369-14-8423587009
  11. V AdityaMR MatranaBJ AtkinsonAL FlahertyE JonaschNM TannirOutcomes of patients with metastatic renal cell carcinoma and end-stage renal disease receiving Dialysis and targeted therapies: a single institution experienceClin Genitourin Cancer201412534835310.1016/j.clgc.2014.01.00424565697
  12. AM CzarneckaM KaweckiF LianJ KornilukC SzczylikFeasibility, efficacy and safety of tyrosine kinase inhibitor treatment in hemodialyzed patients with renal cell cancer: 10 years of experienceFuture Oncol201511162267228210.2217/fon.15.11226260806
  13. K OmaeT KondoT TakagiJ IizukaH KobayashiY HashimotoUse of mammalian target of rapamycin inhibitors after failure of tyrosine kinase inhibitors in patients with metastatic renal cell carcinoma undergoing hemodialysis: a single-center experience with four casesHemodial Int2016203E1E510.1111/hdi.1239026833674
  14. T GrgicL MisJM HammondEverolimus: a new mammalian target of rapamycin inhibitor for the treatment of advanced renal cell carcinomaAnn Pharmacother2011451788310.1345/aph.1M28821177421
  15. F SteinbachAC NovickH ZinckeDP MillerRD WilliamsG LundTreatment of renal cell carcinoma in Von Hippel-Lindau disease: a multicenter studyJ Urol199515361812181610.1016/S0022-5347(01)67318-X7752324
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