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Published in: Cancer Cell International 1/2014

Open Access 01-12-2014 | Primary research

Safety and efficacy of bevacizumab combined with R-CHOP regimen in seven Chinese patients with untreated diffuse large B-cell lymphoma

Authors: Zhiying Fu, Jun Zhu, Wen Zheng, Weiping Liu, Zhitao Ying, Yan Xie, Xiaopei Wang, Ningjing Lin, Meifeng Tu, Lingyan Ping, Lijuan Deng, Chen Zhang, Ning Ding, Yuqin Song

Published in: Cancer Cell International | Issue 1/2014

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Abstract

Background

Rituximab plus CHOP (R-CHOP) significantly improved the outcome of diffuse large B cell lymphoma (DLBCL), a common sub-type of non-Hodgkin lymphoma. But 40% – 50% of DLBCL patients cannot be cured by this regimen. Some clinical trials showed that bevacizumab might be useful in the treatment of DLBCL. This study evaluated the safety and efficacy of bevacizumab combined with the R-CHOP (A-R-CHOP) regimen in Chinese patients with previously untreated DLBCL.

Methods

Patients with previously untreated DLBCL received A-R-CHOP regimen therapy. All patients with complete response (CR)/ unconfirmed complete response(CRu) after 8 cycles of A-R-CHOP received the bevacizumab maintenance therapy once every 3 weeks. The remained bulky disease was treated with radiotherapy.

Results

Seven Chinese patients were treated. All of them had bulky diseases. One patient had progressive disease after 4 cycles of A-R-CHOP therapy. The rest six patients completed 8 cycles of A-R-CHOP treatment. All of these six patients reached CR/CRu (5 CR, 1 CRu). Bevacizumab maintenance therapy was given to 4 CR patients. All 7 patients experienced Grade 3/4 hematologic adverse events; additionally, one had Grade 3 gastrointestinal toxicity and one had Grade 1 epistaxis. During bevacizumab maintenance therapy, one patient had Grade 1 gingival bleeding, another experienced Grade 1 proteinuria and then Grade 3 congestive heart failure 4 months after completion of maintenance therapy. At the end of July 2013, the patient who had progressive disease after 4 cycles of A-R-CHOP died of progressive disease, the other six remained CR response.

Conclusions

The A-R-CHOP regimen is effective for untreated DLBCL, but may cause bevacizumab-specific toxicities, which should be monitored.
Literature
1.
go back to reference Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM: Estimates of worldwide burden of cancer in 2008. Int J Cancer. 2010, 127: 2293-2917.CrossRef Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM: Estimates of worldwide burden of cancer in 2008. Int J Cancer. 2010, 127: 2293-2917.CrossRef
2.
go back to reference Tilly H, Drey LM, ESMO Guidelines Working Group: Diffuse large B-cell non-Hodgkin’s lymphoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010, 21: 172-174. 10.1093/annonc/mdq203.CrossRef Tilly H, Drey LM, ESMO Guidelines Working Group: Diffuse large B-cell non-Hodgkin’s lymphoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010, 21: 172-174. 10.1093/annonc/mdq203.CrossRef
3.
go back to reference Martelli M, Ferreri AJ, Agostinelli C, Di Rocco A, Pfreundschuh M, Pileri SA: Diffuse large B-cell lymphoma. Crit Rev Oncol Hematol. 2013, 87 (2): 146-171. 10.1016/j.critrevonc.2012.12.009.CrossRefPubMed Martelli M, Ferreri AJ, Agostinelli C, Di Rocco A, Pfreundschuh M, Pileri SA: Diffuse large B-cell lymphoma. Crit Rev Oncol Hematol. 2013, 87 (2): 146-171. 10.1016/j.critrevonc.2012.12.009.CrossRefPubMed
4.
go back to reference Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, Lefort S, Marit G, Macro M, Sebban C, Belhadj K, Bordessoule D, Fermé C, Tilly H: Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d’Etudes des Lymphomes de l’Adulte. Blood. 2010, 116 (12): 2040-2045. 10.1182/blood-2010-03-276246.CrossRefPubMedCentralPubMed Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, Lefort S, Marit G, Macro M, Sebban C, Belhadj K, Bordessoule D, Fermé C, Tilly H: Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d’Etudes des Lymphomes de l’Adulte. Blood. 2010, 116 (12): 2040-2045. 10.1182/blood-2010-03-276246.CrossRefPubMedCentralPubMed
5.
go back to reference Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trümper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, Schmitz N, Ruebe C, Feller AC, Loeffler M, German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL): Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomized controlled trial (RICOVER-60). Lancet Oncol. 2008, 9: 105-116. 10.1016/S1470-2045(08)70002-0.CrossRefPubMed Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trümper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, Schmitz N, Ruebe C, Feller AC, Loeffler M, German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL): Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomized controlled trial (RICOVER-60). Lancet Oncol. 2008, 9: 105-116. 10.1016/S1470-2045(08)70002-0.CrossRefPubMed
6.
go back to reference Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N, MabThera InternationalTrial (MInT) Group: CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial Group. Lancet Oncol. 2011, 2: 1013-1022.CrossRef Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N, MabThera InternationalTrial (MInT) Group: CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial Group. Lancet Oncol. 2011, 2: 1013-1022.CrossRef
7.
go back to reference Potti A, Ganti AK, Kargas S, Koch M: Immunohistochemical detection of C-kit (CD117) and vascular endothelial growth factor (VEGF) overexpression in mantle cell lymphoma. Anticancer Res. 2002, 22: 2899-2901.PubMed Potti A, Ganti AK, Kargas S, Koch M: Immunohistochemical detection of C-kit (CD117) and vascular endothelial growth factor (VEGF) overexpression in mantle cell lymphoma. Anticancer Res. 2002, 22: 2899-2901.PubMed
8.
go back to reference Mori F, Ishida T, Ito A, Sato F, Masaki A, Takino H, Ri M, Kusumoto S, Komatsu H, Ueda R, Inagaki H, Iida S: Potent antitumor effects of bevacizumab in a microenvironment-dependent human lymphoma mouse model. Blood Cancer J. 2012, 2 (4): e67-10.1038/bcj.2012.12.CrossRefPubMedCentralPubMed Mori F, Ishida T, Ito A, Sato F, Masaki A, Takino H, Ri M, Kusumoto S, Komatsu H, Ueda R, Inagaki H, Iida S: Potent antitumor effects of bevacizumab in a microenvironment-dependent human lymphoma mouse model. Blood Cancer J. 2012, 2 (4): e67-10.1038/bcj.2012.12.CrossRefPubMedCentralPubMed
10.
go back to reference Stopeck AT, Bellamy W, Unger J, Rimsza L, Iannone M, Fisher RI, Miller TP: Phase II trial of single agent bevacizumab in patients with relapsed, aggressive non-Hodgkin’s lymphoma (NHL): Southwest Oncology Group Study S0108. J Clin Oncol. 2005, 23 (16S): 6592- Stopeck AT, Bellamy W, Unger J, Rimsza L, Iannone M, Fisher RI, Miller TP: Phase II trial of single agent bevacizumab in patients with relapsed, aggressive non-Hodgkin’s lymphoma (NHL): Southwest Oncology Group Study S0108. J Clin Oncol. 2005, 23 (16S): 6592-
11.
go back to reference Stopeck AT, Unger JM, Rimsza LM, Bellamy WT, Iannone M, Persky DO, Leblanc M, Fisher RI, Miller TP: A phase II trial of single agent bevacizumab in patients with relapsed, aggressive non-Hodgkin lymphoma: Southwest Oncology Group Study S0108. Leuk Lymphoma. 2009, 50: 728-735. 10.1080/10428190902856808.CrossRefPubMedCentralPubMed Stopeck AT, Unger JM, Rimsza LM, Bellamy WT, Iannone M, Persky DO, Leblanc M, Fisher RI, Miller TP: A phase II trial of single agent bevacizumab in patients with relapsed, aggressive non-Hodgkin lymphoma: Southwest Oncology Group Study S0108. Leuk Lymphoma. 2009, 50: 728-735. 10.1080/10428190902856808.CrossRefPubMedCentralPubMed
12.
go back to reference Ganjoo KN, An CS, Robertson MJ, Gordon LI, Sen JA, Weisenbach J, Li S, Weller EA, Orazi A, Horning SJ: Rituximab, bevacizumab and CHOP (RA-CHOP) in untreated diffuse large B cell lymphoma: Safety, biomarker and pharmacokinetic analysis. Leuk Lymphoma. 2006, 47: 998-1005. 10.1080/10428190600563821.CrossRefPubMed Ganjoo KN, An CS, Robertson MJ, Gordon LI, Sen JA, Weisenbach J, Li S, Weller EA, Orazi A, Horning SJ: Rituximab, bevacizumab and CHOP (RA-CHOP) in untreated diffuse large B cell lymphoma: Safety, biomarker and pharmacokinetic analysis. Leuk Lymphoma. 2006, 47: 998-1005. 10.1080/10428190600563821.CrossRefPubMed
13.
go back to reference WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue. International Agency for Research on Cancer. Edited by: Swerdlow S, Campo E, Harris NL. 2008, Geneva, Switzerland: World Health Organization WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue. International Agency for Research on Cancer. Edited by: Swerdlow S, Campo E, Harris NL. 2008, Geneva, Switzerland: World Health Organization
14.
go back to reference Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP: Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphomas. J Clin Oncol. 1999, 17: 2351-2352. Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP: Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphomas. J Clin Oncol. 1999, 17: 2351-2352.
16.
go back to reference Geiger-Gritsch S, Stollenwerk B, Miksad R, Guba B, Wild C, Siebert U: Safety of bevacizumab in patients with advanced cancer:a meta-analysis of randomized controlled trial. Oncologist. 2010, 15 (12): 1179-1191.CrossRefPubMedCentralPubMed Geiger-Gritsch S, Stollenwerk B, Miksad R, Guba B, Wild C, Siebert U: Safety of bevacizumab in patients with advanced cancer:a meta-analysis of randomized controlled trial. Oncologist. 2010, 15 (12): 1179-1191.CrossRefPubMedCentralPubMed
17.
go back to reference Ganjoo K, Hong F, Horning SJ, Gascoyne RD, Natkunam Y, Swinnen LJ, Habermann TM, Kahl BS, Advani RH: Bevacizumab and CHOP (a-CHOP) in combination for patients with peripheral T-cell or natural killer cell neoplasms: an Eastern Cooperative group study (E2404). Leuk Lymphoma. in press Ganjoo K, Hong F, Horning SJ, Gascoyne RD, Natkunam Y, Swinnen LJ, Habermann TM, Kahl BS, Advani RH: Bevacizumab and CHOP (a-CHOP) in combination for patients with peripheral T-cell or natural killer cell neoplasms: an Eastern Cooperative group study (E2404). Leuk Lymphoma. in press
18.
go back to reference Stopeck AT, Unger JM, Rimsza LM, LeBlanc M, Farnsworth B, Iannone M, Glenn MJ, Fisher RI, Miller TP: A phase 2 trial of standard-dose cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and rituximab plus bevacizumab for patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: SWOG 0515. Blood. 2012, 120: 1210-1217. 10.1182/blood-2012-04-423079.CrossRefPubMedCentralPubMed Stopeck AT, Unger JM, Rimsza LM, LeBlanc M, Farnsworth B, Iannone M, Glenn MJ, Fisher RI, Miller TP: A phase 2 trial of standard-dose cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and rituximab plus bevacizumab for patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: SWOG 0515. Blood. 2012, 120: 1210-1217. 10.1182/blood-2012-04-423079.CrossRefPubMedCentralPubMed
19.
go back to reference Hapani S, Sher A, Chu D, Wu S: Increased risk of serious hemorrhage with bevacizumab in cancer patients: a meta-analysis. Oncology. 2010, 79: 27-38. 10.1159/000314980.CrossRefPubMed Hapani S, Sher A, Chu D, Wu S: Increased risk of serious hemorrhage with bevacizumab in cancer patients: a meta-analysis. Oncology. 2010, 79: 27-38. 10.1159/000314980.CrossRefPubMed
20.
go back to reference Miles D: Management of toxicity in patients receiving therapy with bevacizumab. EJC. 2008, 6: 9-39. Miles D: Management of toxicity in patients receiving therapy with bevacizumab. EJC. 2008, 6: 9-39.
21.
go back to reference Wu S, Kim C, Baer L, Zhu X: Bevacizumab increases risk for severe proteinuria in cancer patients. J Am Soc Nephrol. 2010, 21: 1381-1389. 10.1681/ASN.2010020167.CrossRefPubMedCentralPubMed Wu S, Kim C, Baer L, Zhu X: Bevacizumab increases risk for severe proteinuria in cancer patients. J Am Soc Nephrol. 2010, 21: 1381-1389. 10.1681/ASN.2010020167.CrossRefPubMedCentralPubMed
22.
go back to reference Eremina V, Jefferson JA, Kowalewska J, Hochster H, Haas M, Weisstuch J, Richardson C, Kopp JB, Kabir MG, Backx PH, Gerber HP, Ferrara N, Barisoni L, Alpers CE, Quaggin SE: VEGF inhibition and renal thrombotic microangiopathy. N Eng J Med. 2008, 358 (11): 1129-1136. 10.1056/NEJMoa0707330.CrossRef Eremina V, Jefferson JA, Kowalewska J, Hochster H, Haas M, Weisstuch J, Richardson C, Kopp JB, Kabir MG, Backx PH, Gerber HP, Ferrara N, Barisoni L, Alpers CE, Quaggin SE: VEGF inhibition and renal thrombotic microangiopathy. N Eng J Med. 2008, 358 (11): 1129-1136. 10.1056/NEJMoa0707330.CrossRef
23.
go back to reference Cheng H, Force T: Molecular mechanisms of cardiovascular toxicity of targeted cancer therapeutics. Circ Res. 2010, 106 (1): 21-34. 10.1161/CIRCRESAHA.109.206920.CrossRefPubMed Cheng H, Force T: Molecular mechanisms of cardiovascular toxicity of targeted cancer therapeutics. Circ Res. 2010, 106 (1): 21-34. 10.1161/CIRCRESAHA.109.206920.CrossRefPubMed
24.
25.
go back to reference Vaklavas C, Lenihan D, Kurarock R, Tsimberidou AM: Anti-vascular endothelial growth factor therapies and cardiovascular toxicity: what are the important clinical markers to target?. Oncologist. 2010, 15: 130-141. 10.1634/theoncologist.2009-0252.CrossRefPubMedCentralPubMed Vaklavas C, Lenihan D, Kurarock R, Tsimberidou AM: Anti-vascular endothelial growth factor therapies and cardiovascular toxicity: what are the important clinical markers to target?. Oncologist. 2010, 15: 130-141. 10.1634/theoncologist.2009-0252.CrossRefPubMedCentralPubMed
26.
go back to reference Hawkes EA, Okines AF, Plummer C, Cunningham D: Cardiotoxicity in patients treated with bevacizumab is potentially reversible. J Clin Oncol. 2011, 29: 560-562. 10.1200/JCO.2011.35.5008.CrossRef Hawkes EA, Okines AF, Plummer C, Cunningham D: Cardiotoxicity in patients treated with bevacizumab is potentially reversible. J Clin Oncol. 2011, 29: 560-562. 10.1200/JCO.2011.35.5008.CrossRef
Metadata
Title
Safety and efficacy of bevacizumab combined with R-CHOP regimen in seven Chinese patients with untreated diffuse large B-cell lymphoma
Authors
Zhiying Fu
Jun Zhu
Wen Zheng
Weiping Liu
Zhitao Ying
Yan Xie
Xiaopei Wang
Ningjing Lin
Meifeng Tu
Lingyan Ping
Lijuan Deng
Chen Zhang
Ning Ding
Yuqin Song
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2014
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/1475-2867-14-5

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