Bevacizumab combined with gemcitabine and capecitabine for advanced pancreatic cancer: a phase II study

M Javle, J Yu, C Garrett, A Pande, B Kuvshinoff, A Litwin, J Phelan 3rd, J Gibbs, R Iyer, M Javle, J Yu, C Garrett, A Pande, B Kuvshinoff, A Litwin, J Phelan 3rd, J Gibbs, R Iyer

Abstract

A total of 50 patients with advanced pancreatic cancer were enrolled in a phase II study of bevacizumab 15 mg kg(-1), capecitabine 1300 mg m(-2) daily for 2 weeks and gemcitabine 1000 mg m(-2) weekly 2 times; cycles were repeated every 21 days. Radiological response rate was 22%; progression-free survival and over survival were 5.8 and 9.8 months respectively. Grade 3 or 4 toxicities included neutropaenia (22%), thrombocytopaenia (14%), thromboembolic events (12%), hypertension (8%) and haemorrhage (6%).

Figures

Figure 1
Figure 1
PFS curve (red) with 95% CI (black).
Figure 2
Figure 2
OS curve (red) with 95% CI (black).

References

    1. az-Rubio E, Schmoll HJ (2005) The future development of bevacizumab in colorectal cancer. Oncology 69(Suppl 3): 34–45
    1. Baxter NN, Whitson BA, Tuttle TM (2007) Trends in the treatment and outcome of pancreatic cancer in the United States. Ann Surg Oncol 14: 1320–1326
    1. Black PC, Dinney CP (2007) Bladder cancer angiogenesis and metastasis – translation from murine model to clinical trial. Cancer Metastasis Rev 26: 623–634
    1. Bremnes RM, Camps C, Sirera R (2006) Angiogenesis in non-small cell lung cancer: the prognostic impact of neoangiogenesis and the cytokines VEGF and bFGF in tumours and blood. Lung Cancer 51: 143–158
    1. Bria E, Milella M, Gelibter A, Cuppone F, Pino MS, Ruggeri EM, Carlini P, Nistico C, Terzoli E, Cognetti F, Giannarelli D (2007) Gemcitabine-based combinations for inoperable pancreatic cancer: have we made real progress? A meta-analysis of 20 phase 3 trials. Cancer 110: 525–533
    1. Burris III HA, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, Von Hoff DD (1997) Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15: 2403–2413
    1. Chen HX (2004) Expanding the clinical development of bevacizumab. Oncologist 9(Suppl 1): 27–35
    1. Deryugina EI, Soroceanu L, Strongin AY (2002) Up-regulation of vascular endothelial growth factor by membrane-type 1 matrix metalloproteinase stimulates human glioma xenograft growth and angiogenesis. Cancer Res 62: 580–588
    1. Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9: 669–676
    1. Halm U, Schumann T, Schiefke I, Witzigmann H, Mossner J, Keim V (2000) Decrease of CA 19-9 during chemotherapy with gemcitabine predicts survival time in patients with advanced pancreatic cancer. Br J Cancer 82: 1013–1016
    1. 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 24: 3946–3952
    1. 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: 2212–2217
    1. Huang SM, Lee JC, Wu TJ, Chow NH (2001) Clinical relevance of vascular endothelial growth factor for thyroid neoplasms. World J Surg 25: 302–306
    1. Hurwitz H, Saini S (2006) Bevacizumab in the treatment of metastatic colorectal cancer: safety profile and management of adverse events. Semin Oncol 33: S26–S34
    1. Kindler HL, Friberg G, Singh DA, Locker G, Nattam S, Kozloff M, Taber DA, Karrison T, Dachman A, Stadler WM, Vokes EE (2005b) Phase II trial of bevacizumab plus gemcitabine in patients with advanced pancreatic cancer. J Clin Oncol 23: 8033–8040
    1. Kindler HL, Friberg G, Singh DA, Locker G, Nattam S, Kozloff M, Taber DA, Karrison T, Dachman A, Stadler WM, Vokes EE (2005a) Phase II trial of bevacizumab plus gemcitabine in patients with advanced pancreatic cancer. J Clin Oncol 23: 8033–8040
    1. Kindler HL, Niedzwiecki D, Hollis D, Oraefo E, Schrag D, Hurwitz H, McLeod HL, Mulcahy MF, Schilsky RL, Goldberg RM, Cancer and Leukemia Group (2007) A double-blind, placebo-controlled, randomized phase III trial of gemcitabine (G) plus bevacizumab (B) versus gemcitabine plus placebo (P) in patients (pts) with advanced pancreatic cancer (PC): a preliminary analysis of Cancer and Leukemia Group B (CALGB). J Clin Oncol (Meeting Abstracts) 25: 4508
    1. Ko AH, Hwang J, Venook AP, Abbruzzese JL, Bergsland EK, Tempero MA (2005) Serum CA 19-9 response as a surrogate for clinical outcome in patients receiving fixed-dose rate gemcitabine for advanced pancreatic cancer. Br J Cancer 93: 195–199
    1. Louvet C, Labianca R, Hammel P, Lledo G, Zampino MG, Andre T, Zaniboni A, Ducreux M, Aitini E, Taieb J, Faroux R, Lepere C, de GA (2005) Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol 23: 3509–3516
    1. Margolin K, Gordon MS, Holmgren E, Gaudreault J, Novotny W, Fyfe G, Adelman D, Stalter S, Breed J (2001) Phase Ib trial of intravenous recombinant humanized monoclonal antibody to vascular endothelial growth factor in combination with chemotherapy in patients with advanced cancer: pharmacologic and long-term safety data. J Clin Oncol 19: 851–856
    1. Ozdemir F, Akdogan R, Aydin F, Reis A, Kavgaci H, Gul S, Akdogan E (2006) The effects of VEGF and VEGFR-2 on survival in patients with gastric cancer. J Exp Clin Cancer Res 25: 83–88
    1. Rocha Lima CM, Green MR, Rotche R, Miller Jr WH., Jeffrey GM, Cisar LA, Morganti A, Orlando N, Gruia G, Miller LL (2004) Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate. J Clin Oncol 22: 3776–3783
    1. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355: 2542–2550
    1. Soh EY, Eigelberger MS, Kim KJ, Wong MG, Young DM, Clark OH, Duh QY (2000) Neutralizing vascular endothelial growth factor activity inhibits thyroid cancer growth in vivo. Surgery 128: 1059–1065
    1. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van GM, 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: 205–216
    1. Van Cutsem E, Vervenne WL, Bennouna J, Humblet Y, Gill S, Van Laethem JL, Verslype C, Scheithauer W, Shang A, Cosaert J, Moore MJ (2009) Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. J Clin Oncol 27(13): 2231–2237
    1. Yoshiji H, Gomez DE, Shibuya M, Thorgeirsson UP (1996) Expression of vascular endothelial growth factor, its receptor, and other angiogenic factors in human breast cancer. Cancer Res 56: 2013–2016

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa