Skip to main content

Advertisement

SpringerLink
Log in

Phase I trial of vandetanib in combination with gemcitabine and capecitabine in patients with advanced solid tumors with an expanded cohort in pancreatic and biliary cancers

  • PHASE I STUDIES
  • Published:
Investigational New Drugs Aims and scope Submit manuscript

Summary

Background Vandetanib is a multitargeted tyrosine kinase inhibitor that affects vascular endothelial growth factor receptor (VEGF), epidermal growth factor (EGF), and rearranged during transfection (RET) mediated receptors which are important for growth and invasion of biliary and pancreatic cancers. This phase I study evaluated the safety profile of vandetanib in combination with standard doses of gemcitabine and capecitabine in order to determine the maximum tolerated dose (MTD). Methods In this single center phase I trial, patients received gemcitabine intravenously (IV) at 1000 mg/m2 days 1, 8, 15 in a 28 day cycle, capecitabine orally at 850 mg/m2 twice daily on days 1–21, and escalating doses of vandetanib (200 or 300 mg orally daily). Once the MTD was defined, an expansion cohort of patients with advanced biliary cancers and locally advanced or metastatic pancreatic cancer was enrolled. Blood samples were also collected at predetermined time points for biomarker analysis. Results Twenty-three patients were enrolled: 9 in the dose escalation and 14 in the dose expansion cohort. One dose limiting toxicity (DLT), of grade 4 neutropenia, occurred in the 200 mg vandetanib cohort. The most common adverse effects were diarrhea (39 %), nausea and vomiting (34 %), and rash (33 %). There were 3 partial responses and stable disease of >2 months (range 2–45, median 5) was observed in 15/23 patients. There was no association between changes in biomarker analytes and disease response. Conclusion The combination of gemcitabine, capecitabine and vandetanib is well tolerated at the recommended phase II dose of gemcitabine 1000 mg/m2 weekly for three consecutive weeks, capecitabine 850 mg/m2 BID days 1–21, and vandetanib 300 mg daily, every 28 days. This combination demonstrated promising activity in pancreaticobiliary cancers and further evaluation is warranted in these diseases. NCT00551096.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63(1):11–30. doi:10.3322/caac.21166

    Article  PubMed  Google Scholar 

  2. Burris H, Storniolo AM (1997) Assessing clinical benefit in the treatment of pancreas cancer: gemcitabine compared to 5-fluorouracil. Eur J Cancer 33(Suppl 1):S18–22

    Article  CAS  PubMed  Google Scholar 

  3. Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W (2007) Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 25(15):1960–1966. doi:10.1200/JCO.2006.07.9525

    Article  CAS  PubMed  Google Scholar 

  4. Colucci G, Labianca R, Di Costanzo F, Gebbia V, Carteni G, Massidda B, Dapretto E, Manzione L, Piazza E, Sannicolo M, Ciaparrone M, Cavanna L, Giuliani F, Maiello E, Testa A, Pederzoli P, Falconi M, Gallo C, Di Maio M, Perrone F (2010) Randomized phase III trial of gemcitabine plus cisplatin compared with single-agent gemcitabine as first-line treatment of patients with advanced pancreatic cancer: the GIP-1 study. J Clin Oncol: Off J Am Soc Clin Oncol 28(10):1645–1651. doi:10.1200/JCO.2009.25.4433

    Article  CAS  Google Scholar 

  5. Heinemann V, Quietzsch D, Gieseler F, Gonnermann M, Schonekas H, Rost A, Neuhaus H, Haag C, Clemens M, Heinrich B, Vehling-Kaiser U, Fuchs M, Fleckenstein D, Gesierich W, Uthgenannt D, Einsele H, Holstege A, Hinke A, Schalhorn A, Wilkowski R (2006) Randomized phase III trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer. J Clin Oncol: Off J Am Soc Clin Oncol 24(24):3946–3952. doi:10.1200/JCO.2005.05.1490

    Article  CAS  Google Scholar 

  6. Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardiere C, Bennouna J, Bachet JB, Khemissa-Akouz F, Pere-Verge D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364(19):1817–1825. doi:10.1056/NEJMoa1011923

    Article  CAS  PubMed  Google Scholar 

  7. Von Hoff DD, Ervin TJ, Arena FP, Chiorean EG, Infante JR, Moor MJ (2013) Results of a randomized phase III trial (MPACT) of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone for patients with metastatic adenocarcinoma of the pancreas with PET and CA19-9 correlates. J Clin Oncol 31:abstract 4005

  8. Hess V, Salzberg M, Borner M, Morant R, Roth AD, Ludwig C, Herrmann R (2003) Combining capecitabine and gemcitabine in patients with advanced pancreatic carcinoma: a phase I/II trial. J Clin Oncol 21(1):66–68

    Article  CAS  PubMed  Google Scholar 

  9. Cunningham D, Chau I, Stocken DD, Valle JW, Smith D, Steward W, Harper PG, Dunn J, Tudur-Smith C, West J, Falk S, Crellin A, Adab F, Thompson J, Leonard P, Ostrowski J, Eatock M, Scheithauer W, Herrmann R, Neoptolemos JP (2009) Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol 27(33):5513–5518. doi:10.1200/JCO.2009.24.2446

    Article  CAS  PubMed  Google Scholar 

  10. Herrmann R, Bodoky G, Ruhstaller T, Glimelius B, Bajetta E, Schuller J, Saletti P, Bauer J, Figer A, Pestalozzi B, Kohne CH, Mingrone W, Stemmer SM, Tamas K, Kornek GV, Koeberle D, Cina S, Bernhard J, Dietrich D, Scheithauer W (2007) Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group. J Clin Oncol 25(16):2212–2217. doi:10.1200/JCO.2006.09.0886

    Article  CAS  PubMed  Google Scholar 

  11. Scheithauer W, Schull B, Ulrich-Pur H, Schmid K, Raderer M, Haider K, Kwasny W, Depisch D, Schneeweiss B, Lang F, Kornek GV (2003) Biweekly high-dose gemcitabine alone or in combination with capecitabine in patients with metastatic pancreatic adenocarcinoma: a randomized phase II trial. Ann Oncol 14(1):97–104

    Article  CAS  PubMed  Google Scholar 

  12. Woodburn JR (1999) The epidermal growth factor receptor and its inhibition in cancer therapy. Pharmacol Ther 82(2–3):241–250

    Article  CAS  PubMed  Google Scholar 

  13. Petit AM, Rak J, Hung MC, Rockwell P, Goldstein N, Fendly B, Kerbel RS (1997) Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solid tumors. Am J Pathol 151(6):1523–1530

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9(6):669–676. doi:10.1038/nm0603-669

    Article  CAS  PubMed  Google Scholar 

  15. Valsecchi ME, McDonald M, Brody JR, Hyslop T, Freydin B, Yeo CJ, Solomides C, Peiper SC, Witkiewicz AK (2012) Epidermal growth factor receptor and insulinlike growth factor 1 receptor expression predict poor survival in pancreatic ductal adenocarcinoma. Cancer 118(14):3484–3493. doi:10.1002/cncr.26661

    Article  CAS  PubMed  Google Scholar 

  16. Lee CS, Pirdas A (1995) Epidermal growth factor receptor immunoreactivity in gallbladder and extrahepatic biliary tract tumours. Pathol Res Pract 191(11):1087–1091. doi:10.1016/S0344-0338(11)80652-7

    Article  CAS  PubMed  Google Scholar 

  17. Kaufman M, Mehrotra B, Limaye S, White S, Fuchs A, Lebowicz Y, Nissel-Horowitz S, Thomas A (2008) EGFR expression in gallbladder carcinoma in North America. Int J Med Sci 5(5):285–291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Hoffmann AC, Goekkurt E, Danenberg PV, Lehmann S, Ehninger G, Aust DE, Stoehlmacher-Williams J (2013) EGFR, FLT1 and heparanase as markers identifying patients at risk of short survival in cholangiocarcinoma. PLoS ONE 8(5), e64186. doi:10.1371/journal.pone.0064186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Tang D, Nagano H, Yamamoto H, Wada H, Nakamura M, Kondo M, Ota H, Yoshioka S, Kato H, Damdinsuren B, Marubashi S, Miyamoto A, Takeda Y, Umeshita K, Dono K, Wakasa K, Monden M (2006) Angiogenesis in cholangiocellular carcinoma: expression of vascular endothelial growth factor, angiopoietin-1/2, thrombospondin-1 and clinicopathological significance. Oncol Rep 15(3):525–532

    CAS  PubMed  Google Scholar 

  20. Yoshikawa D, Ojima H, Iwasaki M, Hiraoka N, Kosuge T, Kasai S, Hirohashi S, Shibata T (2008) Clinicopathological and prognostic significance of EGFR, VEGF, and HER2 expression in cholangiocarcinoma. Br J Cancer 98(2):418–425. doi:10.1038/sj.bjc.6604129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Zorgetto VA, Silveira GG, Oliveira-Costa JP, Soave DF, Soares FA, Ribeiro-Silva A (2013) The relationship between lymphatic vascular density and vascular endothelial growth factor A (VEGF-A) expression with clinical-pathological features and survival in pancreatic adenocarcinomas. Diagn Pathol 8(1):170. doi:10.1186/1746-1596-8-170

    Article  PubMed  PubMed Central  Google Scholar 

  22. Sawai H, Okada Y, Kazanjian K, Kim J, Hasan S, Hines OJ, Reber HA, Hoon DS, Eibl G (2005) The G691S RET polymorphism increases glial cell line-derived neurotrophic factor-induced pancreatic cancer cell invasion by amplifying mitogen-activated protein kinase signaling. Cancer Res 65(24):11536–11544. doi:10.1158/0008-5472.CAN-05-2843

    Article  CAS  PubMed  Google Scholar 

  23. Iwahashi N, Nagasaka T, Tezel G, Iwashita T, Asai N, Murakumo Y, Kiuchi K, Sakata K, Nimura Y, Takahashi M (2002) Expression of glial cell line-derived neurotrophic factor correlates with perineural invasion of bile duct carcinoma. Cancer 94(1):167–174. doi:10.1002/cncr.10169

    Article  CAS  PubMed  Google Scholar 

  24. Mulligan LM (2014) RET revisited: expanding the oncogenic portfolio. Nat Rev Cancer 14(3):173–186. doi:10.1038/nrc3680

    Article  CAS  PubMed  Google Scholar 

  25. Wedge SR, Ogilvie DJ, Dukes M, Kendrew J, Chester R, Jackson JA, Boffey SJ, Valentine PJ, Curwen JO, Musgrove HL, Graham GA, Hughes GD, Thomas AP, Stokes ES, Curry B, Richmond GH, Wadsworth PF, Bigley AL, Hennequin LF (2002) ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res 62(16):4645–4655

    CAS  PubMed  Google Scholar 

  26. Carlomagno F, Vitagliano D, Guida T, Ciardiello F, Tortora G, Vecchio G, Ryan AJ, Fontanini G, Fusco A, Santoro M (2002) ZD6474, an orally available inhibitor of KDR tyrosine kinase activity, efficiently blocks oncogenic RET kinases. Cancer Res 62(24):7284–7290

    CAS  PubMed  Google Scholar 

  27. Ciardiello F, Caputo R, Damiano V, Troiani T, Vitagliano D, Carlomagno F, Veneziani BM, Fontanini G, Bianco AR, Tortora G (2003) Antitumor effects of ZD6474, a small molecule vascular endothelial growth factor receptor tyrosine kinase inhibitor, with additional activity against epidermal growth factor receptor tyrosine kinase. Clin Cancer Res 9(4):1546–1556

    CAS  PubMed  Google Scholar 

  28. Holden SN, Eckhardt SG, Basser R, de Boer R, Rischin D, Green M, Rosenthal MA, Wheeler C, Barge A, Hurwitz HI (2005) Clinical evaluation of ZD6474, an orally active inhibitor of VEGF and EGF receptor signaling, in patients with solid, malignant tumors. Ann Oncol 16(8):1391–1397. doi:10.1093/annonc/mdi247

    Article  CAS  PubMed  Google Scholar 

  29. Heymach JV, Johnson BE, Prager D, Csada E, Roubec J, Pesek M, Spasova I, Belani CP, Bodrogi I, Gadgeel S, Kennedy SJ, Hou J, Herbst RS (2007) Randomized, placebo-controlled phase II study of vandetanib plus docetaxel in previously treated non small-cell lung cancer. J Clin Oncol 25(27):4270–4277. doi:10.1200/JCO.2006.10.5122

    Article  CAS  PubMed  Google Scholar 

  30. Kovacs MJ, Reece DE, Marcellus D, Meyer RM, Mathews S, Dong RP, Eisenhauer E (2006) A phase II study of ZD6474 (Zactima, a selective inhibitor of VEGFR and EGFR tyrosine kinase in patients with relapsed multiple myeloma--NCIC CTG IND.145. Invest New Drugs 24(6):529–535. doi:10.1007/s10637-006-9022-7

    CAS  PubMed  Google Scholar 

  31. Miller KD, Trigo JM, Wheeler C, Barge A, Rowbottom J, Sledge G, Baselga J (2005) A multicenter phase II trial of ZD6474, a vascular endothelial growth factor receptor-2 and epidermal growth factor receptor tyrosine kinase inhibitor, in patients with previously treated metastatic breast cancer. Clin Cancer Res 11(9):3369–3376. doi:10.1158/1078-0432.CCR-04-1923

    Article  CAS  PubMed  Google Scholar 

  32. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92(3):205–216

    Article  CAS  PubMed  Google Scholar 

  33. Kindler HL, Friberg G, Singh DA, Locker G, Nattam S, Kozloff M, Taber DA, Karrison T, Dachman A, Stadler WM, Vokes EE (2005) Phase II trial of bevacizumab plus gemcitabine in patients with advanced pancreatic cancer. J Clin Oncol: Off J Am Soc Clin Oncol 23(31):8033–8040. doi:10.1200/JCO.2005.01.9661

    Article  CAS  Google Scholar 

  34. Ahn J, Wee WR, Lee JH, Hyon JY (2011) Vortex keratopathy in a patient receiving vandetanib for non-small cell lung cancer. Korean J Ophthalmol 25(5):355–357. doi:10.3341/kjo.2011.25.5.355

    Article  PubMed  PubMed Central  Google Scholar 

  35. Tullo AB, Esmaeli B, Murray PI, Bristow E, Forsythe BJ, Faulkner K (2005) Ocular findings in patients with solid tumours treated with the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib (‘Iressa’, ZD1839) in Phase I and II clinical trials. Eye 19(7):729–738. doi:10.1038/sj.eye.6701630

    Article  CAS  PubMed  Google Scholar 

  36. Herbst RS, Heymach JV, O’Reilly MS, Onn A, Ryan AJ (2007) Vandetanib (ZD6474): an orally available receptor tyrosine kinase inhibitor that selectively targets pathways critical for tumor growth and angiogenesis. Expert Opin Investig Drugs 16(2):239–249. doi:10.1517/13543784.16.2.239

    Article  CAS  PubMed  Google Scholar 

  37. Herbst RS, Sun Y, Eberhardt WE, Germonpre P, Saijo N, Zhou C, Wang J, Li L, Kabbinavar F, Ichinose Y, Qin S, Zhang L, Biesma B, Heymach JV, Langmuir P, Kennedy SJ, Tada H, Johnson BE (2010) Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial. Lancet Oncol 11(7):619–626. doi:10.1016/S1470-2045(10)70132-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Wells SA Jr, Gosnell JE, Gagel RF, Moley J, Pfister D, Sosa JA, Skinner M, Krebs A, Vasselli J, Schlumberger M (2010) Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer. J Clin Oncol 28(5):767–772. doi:10.1200/JCO.2009.23.6604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Saletti P, Sessa C, De Dosso S, Cerny T, Renggli V, Koeberle D (2011) Phase I dose-finding study of vandetanib in combination with gemcitabine in locally advanced unresectable or metastatic pancreatic adenocarcinoma. Oncology 81(1):50–54. doi:10.1159/000330769

    Article  CAS  PubMed  Google Scholar 

  40. Cabebe EC, Fisher GA, Sikic BI (2012) A phase I trial of vandetanib combined with capecitabine, oxaliplatin and bevacizumab for the first-line treatment of metastatic colorectal cancer. Invest New Drugs 30(3):1082–1087. doi:10.1007/s10637-011-9656-y

    Article  CAS  PubMed  Google Scholar 

  41. Blackhall FH, O’Brien M, Schmid P, Nicolson M, Taylor P, Milenkova T, Kennedy SJ, Thatcher N (2010) A phase I study of Vandetanib in combination with vinorelbine/cisplatin or gemcitabine/cisplatin as first-line treatment for advanced non-small cell lung cancer. J Thorac Oncol: Off Publ Int Assoc Study Lung Cancer 5(8):1285–1288. doi:10.1097/JTO.0b013e3181e3a2d1

    Article  Google Scholar 

  42. Saunders MP, Wilson R, Peeters M, Smith R, Godwood A, Oliver S, Van Cutsem E (2009) Vandetanib with FOLFIRI in patients with advanced colorectal adenocarcinoma: results from an open-label, multicentre Phase I study. Cancer Chemother Pharmacol 64(4):665–672. doi:10.1007/s00280-008-0914-4

    Article  CAS  PubMed  Google Scholar 

  43. Kiura K, Nakagawa K, Shinkai T, Eguchi K, Ohe Y, Yamamoto N, Tsuboi M, Yokota S, Seto T, Jiang H, Nishio K, Saijo N, Fukuoka M (2008) A randomized, double-blind, phase IIa dose-finding study of Vandetanib (ZD6474) in Japanese patients with non-small cell lung cancer. J Thorac Oncol: Off Publ Int Assoc Study Lung Cancer 3(4):386–393. doi:10.1097/JTO.0b013e318168d228

    Article  Google Scholar 

  44. Hennequin LF, Stokes ES, Thomas AP, Johnstone C, Ple PA, Ogilvie DJ, Dukes M, Wedge SR, Kendrew J, Curwen JO (2002) Novel 4-anilinoquinazolines with C-7 basic side chains: design and structure activity relationship of a series of potent, orally active, VEGF receptor tyrosine kinase inhibitors. J Med Chem 45(6):1300–1312

    Article  CAS  PubMed  Google Scholar 

  45. Langmuir PB, Yver A (2012) Vandetanib for the treatment of thyroid cancer. Clin Pharmacol Ther 91(1):71–80. doi:10.1038/clpt.2011.272

    Article  CAS  PubMed  Google Scholar 

  46. Ichihara E, Ohashi K, Takigawa N, Osawa M, Ogino A, Tanimoto M, Kiura K (2009) Effects of vandetanib on lung adenocarcinoma cells harboring epidermal growth factor receptor T790M mutation in vivo. Cancer Res 69(12):5091–5098. doi:10.1158/0008-5472.CAN-08-4204

    Article  CAS  PubMed  Google Scholar 

  47. Vitagliano D, De Falco V, Tamburrino A, Coluzzi S, Troncone G, Chiappetta G, Ciardiello F, Tortora G, Fagin JA, Ryan AJ, Carlomagno F, Santoro M (2011) The tyrosine kinase inhibitor ZD6474 blocks proliferation of RET mutant medullary thyroid carcinoma cells. Endocr Relat Cancer 18(1):1–11. doi:10.1677/ERC-09-0292

    Article  CAS  PubMed  Google Scholar 

  48. Verbeek HH, Alves MM, de Groot JW, Osinga J, Plukker JT, Links TP, Hofstra RM (2011) The effects of four different tyrosine kinase inhibitors on medullary and papillary thyroid cancer cells. J Clin Endocrinol Metab 96(6):E991–995. doi:10.1210/jc.2010-2381

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Funding provided by: This research was conducted with support from the Investigator-Sponsored Study Program of AstraZeneca and K12CA086913-10 (SL): K12 Institutional Training Award (Paul Calabresi Award for Clinical Oncology)

Author information

Authors and Affiliations

  1. Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, MS 8117, 12801 E 17th Avenue, Room 8120, Aurora, CO, 80045, USA

    Elizabeth R. Kessler, S. Gail Eckhardt, Todd M. Pitts, Wells A. Messersmith, Sujatha Nallapreddy, Colin Weekes, Christopher H. Lieu, Madeleine A. Kane & Stephen Leong

  2. University of Colorado Cancer Center, Aurora, Colorado, USA

    Elizabeth R. Kessler, S. Gail Eckhardt, Todd M. Pitts, Erica L. Bradshaw-Pierce, Wells A. Messersmith, Sujatha Nallapreddy, Colin Weekes, Christopher H. Lieu, Madeleine A. Kane, Sarah Eppers, Elizabeth Freas & Stephen Leong

  3. Department of Pharmaceutical Sciences, Skaggs School of Pharmacy, Aurora, CO, USA

    Erica L. Bradshaw-Pierce

  4. Department of Clinical Pharmacy, Skaggs School of Pharmacy, Aurora, CO, USA

    Cindy L. O’byrant

  5. Department of Oncology, University of Alberta, Edmonton, AB, Canada

    Jennifer Spratlin

Authors
  1. Elizabeth R. Kessler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Gail Eckhardt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Todd M. Pitts
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Erica L. Bradshaw-Pierce
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Cindy L. O’byrant
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wells A. Messersmith
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sujatha Nallapreddy
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Colin Weekes
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jennifer Spratlin
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Christopher H. Lieu
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Madeleine A. Kane
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Sarah Eppers
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Elizabeth Freas
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Stephen Leong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stephen Leong.

Additional information

Support: The study was supported by AstraZeneca and K12CA086913-10 (SL)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kessler, E.R., Eckhardt, S.G., Pitts, T.M. et al. Phase I trial of vandetanib in combination with gemcitabine and capecitabine in patients with advanced solid tumors with an expanded cohort in pancreatic and biliary cancers. Invest New Drugs 34, 176–183 (2016). https://doi.org/10.1007/s10637-015-0316-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10637-015-0316-5

Keywords

Search

Navigation