A phase i trial of bortezomib in combination with epirubicin, carboplatin and capecitabine (ECarboX) in advanced oesophagogastric adenocarcinoma

Investigational New Drugs

Volumn 32, Issue 2, 2014, Pages 250-260

  Turkington, R C ^a,c   Purcell, C ^a   James, C R ^a   Millar, J ^a   Napier, E ^a   Law, D ^a,b   Gallagher, R ^b,c   Morris, M ^b,c   Wilson, R H ^a,b,c   Eatock, M M ^a,c  

^a BELFAST CITY HOSPITAL   (United Kingdom)

^b Northern Ireland Cancer Centre   (United Kingdom)

^c QUEEN'S UNIVERSITY BELFAST   (United Kingdom)

Author keywords

Adenocarcinoma; Bortezomib; Chemotherapy; Oesophago gastric cancer

Indexed keywords

BORTEZOMIB; CAPECITABINE; CARBOPLATIN; CISPLATIN; EPIRUBICIN; FLUOROURACIL;

ABDOMINAL PAIN; ADENOCARCINOMA; ADULT; AGED; ALOPECIA; ANEMIA; ANOREXIA; ANTINEOPLASTIC ACTIVITY; ARTICLE; BACKACHE; CANCER COMBINATION CHEMOTHERAPY; CLINICAL ARTICLE; CONSTIPATION; DIARRHEA; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG SAFETY; DRUG TOLERABILITY; DYSPEPSIA; DYSPNEA; ESOPHAGOGASTRIC ADENOCARCINOMA; FATIGUE; FEMALE; FEVER; HAND FOOT SYNDROME; HUMAN; HYPOKALEMIA; HYPOMAGNESEMIA; MALE; MAXIMUM TOLERATED DOSE; MUCOSA INFLAMMATION; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUROPATHY; NEUTROPENIA; PARTIAL GASTRECTOMY; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; TASTE DISORDER; THORAX PAIN; THROMBOCYTOPENIA; TREATMENT RESPONSE; VERTIGO; VOMITING; XEROSTOMIA;

ADENOCARCINOMA; AGED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BORONIC ACIDS; CARBOPLATIN; DEOXYCYTIDINE; EPIRUBICIN; FEMALE; GASTROINTESTINAL NEOPLASMS; HUMANS; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; NEUTROPENIA; PROTEASOME INHIBITORS; PYRAZINES;

EID: 84896377353     PISSN: 01676997     EISSN: 15730646     Source Type: Journal    
DOI: 10.1007/s10637-013-9970-7     Document Type: Article

References (59)

1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127(12):2893-2917
2. CRUK (2012) Cancer Research UK. Cancer Stats Report- Incidence 2009, Cancer Research UK
3. Glimelius B, Ekstrom K, Hoffman K, Graf W, Sjoden PO, Haglund U, Svensson C, Enander LK, Linne T, Sellstrom H, Heuman R (1997) Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Ann Oncol 8(2):163-168
4. Murad AM, Santiago FF, Petroianu A, Rocha PR, Rodrigues MA, Rausch M (1993) Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer. Cancer 72(1):37-41
5. Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR (2008) Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 358(1):36-46
6. Webb A, Cunningham D, Scarffe JH, Harper P, Norman A, Joffe JK, Hughes M, Mansi J, Findlay M, Hill A, Oates J, Nicolson M, Hickish T, O'Brien M, Iveson T, Watson M, Underhill C, Wardley A, Meehan M (1997) Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol 15(1):261-267
7. Wagner AD, Unverzagt S, Grothe W, Kleber G, Grothey A, Haerting J, Fleig WE (2010) Chemotherapy for advanced gastric cancer. Cochrane database of systematic reviews (Online) (3):CD004064
8. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Ruschoff J, Kang YK (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376(9742):687-697
9. Sasaki N, Morisaki T, Hashizume K, Yao T, Tsuneyoshi M, Noshiro H, Nakamura K, Yamanaka T, Uchiyama A, Tanaka M, Katano M (2001) Nuclear factor-kappaB p65 (RelA) transcription factor is constitutively activated in human gastric carcinoma tissue. Clin Cancer Res 7(12):4136-4142
10. Maeda S, Yoshida H, Ogura K, Mitsuno Y, Hirata Y, Yamaji Y, Akanuma M, Shiratori Y, Omata M (2000) H. pylori activates NF-kappaB through a signaling pathway involving IkappaB kinases, NF-kappaB-inducing kinase, TRAF2, and TRAF6 in gastric cancer cells. Gastroenterology 119(1):97-108
11. O'Riordan JM, Abdel-latif MM, Ravi N, McNamara D, Byrne PJ, McDonald GS, Keeling PW, Kelleher D, Reynolds JV (2005) Proinflammatory cytokine and nuclear factor kappa-B expression along the inflammation-metaplasia-dysplasia- adenocarcinoma sequence in the esophagus. Am J Gastroenterol 100(6):1257-1264
12. Wang W, Luo HS, Yu BP (2004) Expression of NF-kappaB and human telomerase reverse transcriptase in gastric cancer and precancerous lesions. World J Gastroenterol 10(2):177-181
13. Cao HJ, Fang Y, Zhang X, Chen WJ, Zhou WP, Wang H, Wang LB, Wu JM (2005) Tumor metastasis and the reciprocal regulation of heparanase gene expression by nuclear factor kappa B in human gastric carcinoma tissue. World J Gastroenterol 11(6):903-907
14. Wu L, Pu Z, Feng J, Li G, Zheng Z, Shen W (2008) The ubiquitin-proteasome pathway and enhanced activity of NF-kappaB in gastric carcinoma. J Surg Oncol 97(5):439-444
15. Izzo JG, Malhotra U, Wu TT, Ensor J, Luthra R, Lee JH, Swisher SG, Liao Z, Chao KS, Hittelman WN, Aggarwal BB, Ajani JA (2006) Association of activated transcription factor nuclear factor kappab with chemoradiation resistance and poor outcome in esophageal carcinoma. J Clin Oncol 24(5):748-754
16. Pahl HL (1999) Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene 18(49):6853-6866
17. Camp ER, Li J, Minnich DJ, Brank A, Moldawer LL, MacKay SL, Hochwald SN (2004) Inducible nuclear factor-kappaB activation contributes to chemotherapy resistance in gastric cancer. J Am Coll Surg 199(2):249-258
18. Li J, Minnich DJ, Camp ER, Brank A, Mackay SL, Hochwald SN (2006) Enhanced sensitivity to chemotherapy in esophageal cancer through inhibition of NF-kappaB. J Surg Res 132(1):112-120
19. Adams J, Palombella VJ, Sausville EA, Johnson J, Destree A, Lazarus DD, Maas J, Pien CS, Prakash S, Elliott PJ (1999) Proteasome inhibitors: a novel class of potent and effective antitumor agents. Cancer Res 59(11):2615-2622
20. Almond JB, Cohen GM (2002) The proteasome: a novel target for cancer chemotherapy. Leukemia 16(4):433-443
21. Cusack JC (2003) Rationale for the treatment of solid tumors with the proteasome inhibitor bortezomib. Cancer Treat Rev 29(Suppl 1):21-31
22. Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, Harousseau JL, Ben-Yehuda D, Lonial S, Goldschmidt H, Reece D, San-Miguel JF, Blade J, Boccadoro M, Cavenagh J, Dalton WS, Boral AL, Esseltine DL, Porter JB, Schenkein D, Anderson KC (2005) Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 352(24):2487-2498
23. Teicher BA, Ara G, Herbst R, Palombella VJ, Adams J (1999) The proteasome inhibitor PS-341 in cancer therapy. Clin Cancer Res 5(9):2638-2645
24. Cusack JC Jr, Liu R, Houston M, Abendroth K, Elliott PJ, Adams J, Baldwin AS Jr (2001) Enhanced chemosensitivity to CPT-11 with proteasome inhibitor PS-341: implications for systemic nuclear factor-kappaB inhibition. Cancer Res 61(9):3535-3540
25. San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, Spicka I, Petrucci MT, Palumbo A, Samoilova OS, Dmoszynska A, Abdulkadyrov KM, Schots R, Jiang B, Mateos MV, Anderson KC, Esseltine DL, Liu K, Cakana A, van de Velde H, Richardson PG (2008) Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 359(9):906-917
26. Nawrocki ST, Sweeney-Gotsch B, Takamori R, McConkey DJ (2004) The proteasome inhibitor bortezomib enhances the activity of docetaxel in orthotopic human pancreatic tumor xenografts. Mol Cancer Ther 3(1):59-70
27. Williams S, Pettaway C, Song R, Papandreou C, Logothetis C, McConkey DJ (2003) Differential effects of the proteasome inhibitor bortezomib on apoptosis and angiogenesis in human prostate tumor xenografts. Mol Cancer Ther 2(9):835-843
28. Fujita T, Doihara H, Washio K, Ino H, Murakami M, Naito M, Shimizu N (2007) Antitumor effects and drug interactions of the proteasome inhibitor bortezomib (PS341) in gastric cancer cells. Anti-Cancer Drugs 18(6):677-686
29. Bae SH, Ryoo HM, Kim MK, Lee KH, Sin JI, Hyun MS (2008) Effects of the proteasome inhibitor bortezomib alone and in combination with chemotherapeutic agents in gastric cancer cell lines. Oncol Rep 19(4):1027-1032
30. Nakata W, Hayakawa Y, Nakagawa H, Sakamoto K, Kinoshita H, Takahashi R, Hirata Y, Maeda S, Koike K (2011) Anti-tumor activity of the proteasome inhibitor bortezomib in gastric cancer. Int J Oncol 39(6):1529-1536
31. Dy GK, Thomas JP, Wilding G, Bruzek L, Mandrekar S, Erlichman C, Alberti D, Binger K, Pitot HC, Alberts SR, Hanson LJ, Marnocha R, Tutsch K, Kaufmann SH, Adjei AA (2005) A phase I and pharmacologic trial of two schedules of the proteasome inhibitor, PS-341 (bortezomib, velcade), in patients with advanced cancer. Clin Cancer Res 11(9):3410-3416
32. Davies AM, Ruel C, Lara PN, Lau DH, Gumerlock PH, Bold R, Shibata S, Lenz HJ, Schenkein DP, Gandara DR (2008) The proteasome inhibitor bortezomib in combination with gemcitabine and carboplatin in advanced non-small cell lung cancer: a California Cancer Consortium Phase I study. J Thorac Oncol 3(1):68-74
33. Ma C, Mandrekar SJ, Alberts SR, Croghan GA, Jatoi A, Reid JM, Hanson LJ, Bruzek L, Tan AD, Pitot HC, Erlichman C, Wright JJ, Adjei AA (2007) A phase I and pharmacologic study of sequences of the proteasome inhibitor, bortezomib (PS-341, Velcade), in combination with paclitaxel and carboplatin in patients with advanced malignancies. Cancer Chemother Pharmacol 59(2):207-215
34. Cohen SJ, Engstrom PF, Lewis NL, Langer CJ, McLaughlin S, Beard M, Weiner LM, Meropol NJ (2008) Phase I study of capecitabine and oxaliplatin in combination with the proteasome inhibitor bortezomib in patients with advanced solid tumors. Am J Clin Oncol 31(1):1-5
35. Cresta S, Sessa C, Catapano CV, Gallerani E, Passalacqua D, Rinaldi A, Bertoni F, Vigano L, Maur M, Capri G, Maccioni E, Tosi D, Gianni L (2008) Phase I study of bortezomib with weekly paclitaxel in patients with advanced solid tumours. Eur J Cancer 44(13):1829-1834
36. LoConte NK, Thomas JP, Alberti D, Heideman J, Binger K, Marnocha R, Utecht K, Geiger P, Eickhoff J, Wilding G, Kolesar J (2008) A phase I pharmacodynamic trial of bortezomib in combination with doxorubicin in patients with advanced cancer. Cancer Chemother Pharmacol 63(1):109-115
37. Iqbal SC, Cole S, Yang P, Lara N, Gumerlock PH (2004) Phase I study of PS-341 (bortezomib) with 5-fluorouracil/leucovorin (5-FU/LV) in advanced solid tumors: A California Cancer Consortium study. J Clin Oncol 22(14s):2057
38. Shah MA, Power DG, Kindler HL, Holen KD, Kemeny MM, Ilson DH, Tang L, Capanu M, Wright JJ, Kelsen DP (2011) A multicenter, phase II study of bortezomib (PS-341) in patients with unresectable or metastatic gastric and gastroesophageal junction adenocarcinoma. Invest New Drugs 29(6):1475-1481
39. Ocean AS-S, Schnoll-Sussman R, Keresztes X, Chen S, Holloway N, Matthews P, Mazumdar M, Wright J, Wadler S (2006) Phase II study of PS-341 (bortezomib) with or without irinotecan in patients (pts) with advanced gastric adenocarcinomas (AGA). J Clin Oncol 24(18S):14040
40. Jatoi A, Dakhil SR, Foster NR, Ma C, Rowland KM Jr, Moore DF Jr, Jaslowski AJ, Thomas SP, Hauge MD, Flynn PJ, Stella PJ, Alberts SR (2008) Bortezomib, paclitaxel, and carboplatin as a first-line regimen for patients with metastatic esophageal, gastric, and gastroesophageal cancer: phase II results from the North Central Cancer Treatment Group (N044B). J Thorac Oncol 3(5):516-520
41. Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA, Mannel RS, DeGeest K, Hartenbach EM, Baergen R (2003) Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol 21(17):3194-3200
42. Taylor AE, Wiltshaw E, Gore ME, Fryatt I, Fisher C (1994) Long-term follow-up of the first randomized study of cisplatin versus carboplatin for advanced epithelial ovarian cancer. J Clin Oncol 12(10):2066-2070
43. Rothermundt C, Hubner R, Ahmad T, Gibbens I, Keyzor C, Habeshaw T, Kaye S, Gore M (2006) Combination chemotherapy with carboplatin, capecitabine and epirubicin (ECarboX) as second- or third-line treatment in patients with relapsed ovarian cancer: a phase I/II trial. Br J Cancer 94(1):74-78
44. Rao S, Starling N, Cunningham D, Benson M, Wotherspoon A, Lupfert C, Kurek R, Oates J, Baselga J, Hill A (2008) Phase I study of epirubicin, cisplatin and capecitabine plus matuzumab in previously untreated patients with advanced oesophagogastric cancer. Br J Cancer 99(6):868-874
45. Duek A, Feldberg E, Haran M, Berrebi A (2007) Pulmonary fibrosis in a myeloma patient on bortezomib treatment. A new severe adverse effect of a new drug. Am J Hematol 82(6):502-503
46. Schnetzler B, Popova N, Collao Lamb C, Sappino AP (2001) Coronary spasm induced by capecitabine. Ann Oncol 12(5):723-724
47. Frickhofen N, Beck FJ, Jung B, Fuhr HG, Andrasch H, Sigmund M (2002) Capecitabine can induce acute coronary syndrome similar to 5-fluorouracil. Ann Oncol 13(5):797-801
48. El-Rayes BF, Shields A, Zalupski M, Heilbrun LK, Jain V, Terry D, Ferris A, Philip PA (2004) A phase II study of carboplatin and paclitaxel in esophageal cancer. Ann Oncol 15(6):960-965
49. Philip PA, Zalupski MM, Gadgeel S, Hussain M, Shields A (1997) A phase II study of carboplatin and paclitaxel in the treatment of patients with advanced esophageal and gastric cancer. Semin Oncol 24(6 Suppl 19):S19-86-S19-88
50. Keresztes RS, Port JL, Pasmantier MW, Korst RJ, Altorki NK (2003) Preoperative chemotherapy for esophageal cancer with paclitaxel and carboplatin: results of a phase II trial. J Thorac Cardiovasc Surg 126(5):1603-1608
51. Wang CY, Mayo MW, Baldwin AS Jr (1996) TNF- and cancer therapy-induced apoptosis: potentiation by inhibition of NF-kappaB. Science (New York, NY) 274(5288):784-787
52. Wang CY, Cusack JC Jr, Liu R, Baldwin AS Jr (1999) Control of inducible chemoresistance: enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-kappaB. Nat Med 5(4):412-417
53. Wang CY, Guttridge DC, Mayo MW, Baldwin AS Jr (1999) NF-kappaB induces expression of the Bcl-2 homologue A1/Bfl-1 to preferentially suppress chemotherapy-induced apoptosis. Mol Cell Biol 19(9):5923-5929
54. DiDonato JA, Mercurio F, Karin M (2012) NF-kappaB and the link between inflammation and cancer. Immunol Rev 246(1):379-400
55. Chaturvedi MM, Sung B, Yadav VR, Kannappan R, Aggarwal BB (2011) NF-kappaB addiction and its role in cancer: 'one size does not fit all'. Oncogene 30(14):1615-1630
56. Markovina S, Callander NS, O'Connor SL, Kim J, Werndli JE, Raschko M, Leith CP, Kahl BS, Kim K, Miyamoto S (2008) Bortezomib-resistant nuclear factor-kappaB activity in multiple myeloma cells. Mol Cancer Res 6(8):1356-1364
57. Dolcet X, Llobet D, Encinas M, Pallares J, Cabero A, Schoenenberger JA, Comella JX, Matias-Guiu X (2006) Proteasome inhibitors induce death but activate NF-kappaB on endometrial carcinoma cell lines and primary culture explants. J Biol Chem 281(31):22118-22130
58. Hideshima T, Ikeda H, Chauhan D, Okawa Y, Raje N, Podar K, Mitsiades C, Munshi NC, Richardson PG, Carrasco RD, Anderson KC (2009) Bortezomib induces canonical nuclear factor-kappaB activation in multiple myeloma cells. Blood 114(5):1046-1052
59. Li C, Chen S, Yue P, Deng X, Lonial S, Khuri FR, Sun SY (2010) Proteasome inhibitor PS-341 (bortezomib) induces calpain-dependent IkappaB(alpha) degradation. J Biol Chem 285(21):16096-16104