ࡱ > } | y )J bjbj . { { )B > > > > > R R R R $ v R 0 J \ \ \ \ 7 7 7 $ P F > 7 7 7 7 7 > > \ \ _ _ _ 7 > \ > \ _ 7 _ _ _ \ = _ 0 _ H H _ H > _ , 7 7 _ 7 7 7 7 7 _ 7 7 7 7 7 7 7 H 7 7 7 7 7 7 7 7 7 : Supplementary Table 1 : Phase II/III trials of chemotherapeutic regimes in neuroendocrine tumours.
Phase II/III trials from year 2000. The number of gastric NETs or tumours of unknown site was recorded where specified.
StudyPhaseAgent NNumber of gastric NETsResultsOtherRinke et al, 2009 ADDIN EN.CITE Rinke200913313313317Rinke, AnjaMller, Hans-HelgeSchade-Brittinger, CarmenKlose, Klaus-JochenBarth, PeterWied, MatthiasMayer, ChristinaAminossadati, BehnazPape, Ulrich-FrankBlker, MichaelHarder, JanArnold, ChristianGress, ThomasArnold, RudolfPlacebo-Controlled, Double-Blind, Prospective, Randomized Study on the Effect of Octreotide LAR in the Control of Tumor Growth in Patients With Metastatic Neuroendocrine Midgut Tumors: A Report From the PROMID Study GroupJournal of Clinical OncologyJournal of Clinical Oncology4656-466327282009October 1, 2009http://jco.ascopubs.org/content/27/28/4656.abstract10.1200/jco.2009.22.851094III (RCT)Octreotide LAR8521 unknown site, all others were midgutStable disease 66.7% versus 37.2% with placeboYao et al, 2008 ADDIN EN.CITE ADDIN EN.CITE.DATA 112
IIBevacizumab
PEG Interferon Alpha-2b
(Monotherapy)446 foregut
1 gastric (2.3%)Bevacizumab
: 18% partial response
77% stable disease
5% disease progression
PEG Intron:
68% stable disease
27% disease progression
Progression free survival at the end of 18weeks monotherapy therapy:
95% Bevacizumab
68% PEG Interferon
Kulke et al, 2008 ADDIN EN.CITE Kulke200816216216217Kulke, Matthew H.Lenz, Heinz-JosefMeropol, Neal J.Posey, JamesRyan, David P.Picus, JoelBergsland, EmilyStuart, KeithTye, LesleyHuang, XinLi, Jim Z.Baum, Charles M.Fuchs, Charles S.Activity of Sunitinib in Patients With Advanced Neuroendocrine TumorsJournal of Clinical OncologyJournal of Clinical Oncology3403-341026202008July 10, 2008http://jco.ascopubs.org/content/26/20/3403.abstract10.1200/jco.2007.15.9020132IISunitinib10714 foregut (lung and stomach); 1 unknownExcluding pancreatic NETs: 2.4% partial response
83% stable diseaseYao et al, 2007 ADDIN EN.CITE Yao200711211211217Yao, James C.Zhang, Jun X.Rashid, AsifYeung, Sai-Ching J.Szklaruk, JanioHess, KennethXie, KepingEllis, LeeAbbruzzese, James L.Ajani, Jaffer A.Clinical and In vitro Studies of Imatinib in Advanced Carcinoid TumorsClinical Cancer ResearchClinical Cancer Research234-2401312007January 1, 2007http://clincancerres.aacrjournals.org/content/13/1/234.abstract10.1158/1078-0432.ccr-06-1618113IIImatinib272 gastric, 7 site unknown1 partial response
17 stable diseaseBajetta et al, 2007 ADDIN EN.CITE Bajetta200716516516517Bajetta, EmilioCatena, LauraProcopio, GiuseppeDe Dosso, SaraBichisao, EttoreFerrari, LeonardoMartinetti, AntoniaPlatania, MarcoVerzoni, ElenaFormisano, BarbaraBajetta, RobertoAre capecitabine and oxaliplatin (XELOX) suitable treatments for progressing low-grade and high-grade neuroendocrine tumours?Cancer Chemotherapy and PharmacologyCancer Chemotherapy and Pharmacology637-642595Medicine2007Springer Berlin / Heidelberg0344-5704http://dx.doi.org/10.1007/s00280-006-0306-610.1007/s00280-006-0306-6133IICapecitabine and oxaliplatin (XELOX)407 site not specified11 partial response
14 stable diseaseDuran et al, 2006 ADDIN EN.CITE Duran200616416416417Duran, I.Kortmansky, J.Singh, D.Hirte, H.Kocha, W.Goss, G.Le, L.Oza, A.Nicklee, T.Ho, J.Birle, D.Pond, G. R.Arboine, D.Dancey, J.Aviel-Ronen, S.Tsao, M. S.Hedley, D.Siu, L. L.A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomasBr J CancerBr J Cancer1148-11549592006Cancer Research UK0007-0920http://dx.doi.org/10.1038/sj.bjc.6603419134IITemsirolimus3621 carcinoids, site not specified1 partial response
12 stable diseasemTOR pathway downregulated; Activity does not warrant further single agent evaluationKulke et al, 2004 ADDIN EN.CITE Kulke200415915915917Kulke, M. H.Kim, H.Clark, J. W.Enzinger, P. C.Lynch, T. J.Morgan, J. A.Vincitore, M.Michelini, A.Fuchs, C. S.Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. matthew_kulke@dfci.harvard.eduA Phase II trial of gemcitabine for metastatic neuroendocrine tumorsCancerCancer934-910152004/08/27AdultAgedAntimetabolites, Antineoplastic/ therapeutic useDeoxycytidine/ analogs & derivatives/ therapeutic useFemaleHumansMaleMiddle AgedNeuroendocrine Tumors/ drug therapy/secondaryPrognosisSurvival RateTreatment Outcome2004Sep 10008-543X (Print)
0008-543X (Linking)1532990010.1002/cncr.20466 [doi]Nlmeng135
IIGemcitabine
(Monotherapy)183 NETs site not specifiedNo partial responses
11 stable disease
Kulke et al, 2006 ADDIN EN.CITE ADDIN EN.CITE.DATA 136
IIIrinotecan
Cisplatin
(Combination therapy)182 site unknown1 partial response
11 stable diseaseRegimen effective in poorly differentiated NETs rather than well differentiated NETsSun et al, 2005 ADDIN EN.CITE Sun200515715715717Sun, WeijingLipsitz, StuartCatalano, PaulMailliard, James A.Haller, Daniel G.Phase II/III Study of Doxorubicin With Fluorouracil Compared With Streptozocin With Fluorouracil or Dacarbazine in the Treatment of Advanced Carcinoid Tumors: Eastern Cooperative Oncology Group Study E1281Journal of Clinical OncologyJournal of Clinical Oncology4897-490423222005August 1, 2005http://jco.ascopubs.org/content/23/22/4897.abstract10.1200/jco.2005.03.616137
II/IIIDoxorubicin with fluorouracil (FU/DOX) or streptozocin with fluorouracil (FU/STZ). [Crossover to dacarbazine (DTIC) after disease progression following first-line treatment] 24930 site not specifiedObjective response rate: FU/DOX 15.9%
FU/STZ 16%
(Not statistically significant P=0.82)
Crossover to DTIC 8.2%Progression free survival statistically significant difference between FU/DOX and FU/STZ on substratified analysis based on performance status. p= 0.013Kulke et al, 2006 ADDIN EN.CITE ADDIN EN.CITE.DATA 110
II/IIITemozolomide
Thalidomide
(Combination therapy)2915 NETs site not specified40% Biochemical response (CgA)
25% overall radiological responseRegimen more active in pancreatic endocrine tumours (45% radiological response rate) than other NETs (7% radiological response rate)Ekeblad et al, 2007 ADDIN EN.CITE Ekeblad200716316316317Ekeblad, SaraSundin, AndersJanson, Eva TiensuuWelin, StaffanGranberg, DanKindmark, HenrikDunder, KristinaKozlovacki, Gordanarlefors, HkanSigurd, Mattiasberg, KjellEriksson, BarbroSkogseid, BrittTemozolomide as Monotherapy Is Effective in Treatment of Advanced Malignant Neuroendocrine TumorsClinical Cancer ResearchClinical Cancer Research2986-299113102007May 15, 2007http://clincancerres.aacrjournals.org/content/13/10/2986.abstract10.1158/1078-0432.ccr-06-2053138Retro-spectiveTemozolomide361 gastric, 1 foregut53% stable diseaseAnsell et al, 2001 ADDIN EN.CITE Ansell200116616616617Ansell, Stephen M.Pitot, Henry C.Burch, Patrick A.Kvols, Larry K.Mahoney, Michelle R.Rubin, JosephA Phase II study of high-dose paclitaxel in patients with advanced neuroendocrine tumorsCancerCancer1543-1548918paclitaxelneuroendocrine tumorscarcinoid tumorislet cell tumor2001John Wiley & Sons, Inc.1097-0142http://dx.doi.org/10.1002/1097-0142(20010415)91:8<1543::AID-CNCR1163>3.0.CO;2-N10.1002/1097-0142(20010415)91:8<1543::aid-cncr1163>3.0.co;2-n139IIPaclitaxel2414 NETs site not specified2 partial response
Disease progressed in remainderActivity does not warrant further single agent evaluationFjallstog et al, 2001 ADDIN EN.CITE Fjllskog200116716716717Fjllskog, Marie-Louise H.Granberg, Dan P. K.Welin, Staffan L. V.Eriksson, ChristopherKjell, E. bergJanson, Eva T.Eriksson, Barbro K.Treatment with cisplatin and etoposide in patients with neuroendocrine tumorsCancerCancer1101-1107925metastatic neuroendocrine tumorschemotherapycisplatinetoposidenephrotoxicity2001John Wiley & Sons, Inc.1097-0142http://dx.doi.org/10.1002/1097-0142(20010901)92:5<1101::AID-CNCR1426>3.0.CO;2-V10.1002/1097-0142(20010901)92:5<1101::aid-cncr1426>3.0.co;2-v140IICisplatin and etoposide3618 foregutOf foregut: 10 partial response
6 stable disease
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