Skip to main content
Top
Published in: Journal of Ovarian Research 1/2012

Open Access 01-12-2012 | Research

A case series of low dose bevacizumab and chemotherapy in heavily pretreated patients with epithelial ovarian cancer

Authors: Carlotta Defferrari, Sara Campora, Mauro D'Amico, Arnoldo Piccardo, Ennio Biscaldi, Daniela Rosselli, Ambra Pasa, Matteo Puntoni, Alberto Gozza, Alessandra Gennari, Silvia Zanardi, Rita Lionetto, Michela Bandelloni, Andrea DeCensi

Published in: Journal of Ovarian Research | Issue 1/2012

Login to get access

Abstract

Background

The addition of bevacizumab to standard chemotherapy prolongs progression free survival in the first line treatment of epithelial ovarian cancer (EOC), but its cost/effectiveness is debated. We assessed the safety and activity of a lower dose of bevacizumab in pretreated advanced stage EOC.

Methods

We treated 15 patients, mostly with platinum resistant EOC, who had received a median of four prior cytotoxic regimens, with bevacizumab 5–7.5 mg/kg q21 days in combination with either carboplatin (n = 8), oral cyclofosfamide (n = 5) or weekly paclitaxel (n = 2). Bevacizumab was administered until disease progression. Tumor response was assessed by CA125 and fusion 18 F-FDG PET/contrast enhanced CT.

Results

The median number of bevacizumab cycles was 21 (range 3–59). The median baseline CA125 was 272 U/ml and decreased to 15.2 U/ml at nadir. Tumor response was 4 complete response (CR) (26.7%) and 7 partial response (PR) (46.7%) by chemotherapy (CT), with an overall response rate of 73.4% (95% CI, 51.0 – 95.8) according to Response Evaluation Criteria In Solid Tumors (RECIST), and 6 CR (40%) and 4 PR (26.7%) by PET, for an overall metabolic response rate of 67% (95%CI, 42.8 – 90.6) according to PET Response Criteria in Solid Tumors (PERCIST). Median progression free survival (PFS) was 21 months and median overall survival (OS) was 24 months. Grade 3 adverse events related to bevacizumab were hypertension (n = 2), proteinuria (n = 1) and epistaxis (n = 5). Treatment was delayed in five patients for nasal bleeding or uncontrolled hypertension.

Conclusions

Low-dose bevacizumab and chemotherapy was well tolerated and active in a heavily pretreated population of advanced EOC. Further studies should assess the activity of low dose bevacizumab in EOC.
Appendix
Available only for authorised users
Literature
1.
go back to reference Ma WW, Adjei AA: Novel agents on the horizon for cancer therapy. CA Cancer J Lin 2009, 59: 111–137. 10.3322/caac.20003CrossRef Ma WW, Adjei AA: Novel agents on the horizon for cancer therapy. CA Cancer J Lin 2009, 59: 111–137. 10.3322/caac.20003CrossRef
2.
go back to reference Folkman J: Tumor angiogenesis: therapeutic implications. N Engl J Med 1971, 285: 1182–1186. 10.1056/NEJM197111182852108PubMedCrossRef Folkman J: Tumor angiogenesis: therapeutic implications. N Engl J Med 1971, 285: 1182–1186. 10.1056/NEJM197111182852108PubMedCrossRef
3.
go back to reference Hiclin DJ, Ellis LM: Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 2005, 23: 1011–1027.CrossRef Hiclin DJ, Ellis LM: Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 2005, 23: 1011–1027.CrossRef
4.
go back to reference Ishigami SI, Arii S, Furutani M, Niwano M, Harada T, Mizumoto M, Mori A, Onodera H, Imamura M: Predictive value of vascular endothelial growth factor (VEGFR) in metastasis and prognosis of human colorectal cancer. Br J Cancer 1998, 78: 1379–1384. 10.1038/bjc.1998.688PubMedCentralPubMedCrossRef Ishigami SI, Arii S, Furutani M, Niwano M, Harada T, Mizumoto M, Mori A, Onodera H, Imamura M: Predictive value of vascular endothelial growth factor (VEGFR) in metastasis and prognosis of human colorectal cancer. Br J Cancer 1998, 78: 1379–1384. 10.1038/bjc.1998.688PubMedCentralPubMedCrossRef
5.
go back to reference Shimogai R, Kigawa J, Itamochi H, Iba T, Kanamori Y, Oishi T, Shimada M, Sato S, Kawaguchi W, Sato S, Terakawa N: Expression of hypoxia-inducible factor 1alha gene affects the outcome in patients with ovarian cancer. Int J Gynecol Cancer 2008, 18: 499–505. 10.1111/j.1525-1438.2007.01055.xPubMedCrossRef Shimogai R, Kigawa J, Itamochi H, Iba T, Kanamori Y, Oishi T, Shimada M, Sato S, Kawaguchi W, Sato S, Terakawa N: Expression of hypoxia-inducible factor 1alha gene affects the outcome in patients with ovarian cancer. Int J Gynecol Cancer 2008, 18: 499–505. 10.1111/j.1525-1438.2007.01055.xPubMedCrossRef
6.
go back to reference Hiroaki I: Targeted therapies in epithelial ovarian cancer: molecular mechanisms of action. World J Biol Chem 2010,1(7):209–220. 10.4331/wjbc.v1.i7.209CrossRef Hiroaki I: Targeted therapies in epithelial ovarian cancer: molecular mechanisms of action. World J Biol Chem 2010,1(7):209–220. 10.4331/wjbc.v1.i7.209CrossRef
7.
go back to reference Burger RA, Sill MW, Monk BJ, Greer BE, Sorosky JI: Phase II: trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: A Ginecologic Oncology Group study. J Clin Oncol 2007, 25: 5165–5171. 10.1200/JCO.2007.11.5345PubMedCrossRef Burger RA, Sill MW, Monk BJ, Greer BE, Sorosky JI: Phase II: trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: A Ginecologic Oncology Group study. J Clin Oncol 2007, 25: 5165–5171. 10.1200/JCO.2007.11.5345PubMedCrossRef
8.
go back to reference Garcia AA, Hirte H, Fleming G, Yang D, Tsao-Wei DD, Roman L, Groshen S, Swenson S, Markland F, Gandara D, Scudder S, Morgan R, Chen H, Lenz HJ, Oza AM: Phase II clinical trial of bevacizumab and low-dose metronomic oral cyclophosphamide in recurrent ovarian cancer: a trial of the California, Chicago, and Princess Margaret Hospital phase II consortia. J Clin Oncol 2008,26(1):76–82. 10.1200/JCO.2007.12.1939PubMedCrossRef Garcia AA, Hirte H, Fleming G, Yang D, Tsao-Wei DD, Roman L, Groshen S, Swenson S, Markland F, Gandara D, Scudder S, Morgan R, Chen H, Lenz HJ, Oza AM: Phase II clinical trial of bevacizumab and low-dose metronomic oral cyclophosphamide in recurrent ovarian cancer: a trial of the California, Chicago, and Princess Margaret Hospital phase II consortia. J Clin Oncol 2008,26(1):76–82. 10.1200/JCO.2007.12.1939PubMedCrossRef
9.
go back to reference Cannistra SA, Phase II: study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol 2007, 25: 5180–5186. 10.1200/JCO.2007.12.0782PubMedCrossRef Cannistra SA, Phase II: study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol 2007, 25: 5180–5186. 10.1200/JCO.2007.12.0782PubMedCrossRef
10.
go back to reference McGonigle KF, Muntz HG, Vuky J, Paley PJ, Veljovich DS, Greer BE, Goff BA, Gray HJ, Malpass TW: Combined weekly topotecan and biweekly bevacizumab in womenwith platinum-resistant ovarian, peritoneal, or fallopian tube cancer: results of a phase 2 study. Cancer 2011,117(16):3731–3740. 10.1002/cncr.25967PubMedCrossRef McGonigle KF, Muntz HG, Vuky J, Paley PJ, Veljovich DS, Greer BE, Goff BA, Gray HJ, Malpass TW: Combined weekly topotecan and biweekly bevacizumab in womenwith platinum-resistant ovarian, peritoneal, or fallopian tube cancer: results of a phase 2 study. Cancer 2011,117(16):3731–3740. 10.1002/cncr.25967PubMedCrossRef
11.
go back to reference Kudoh K, Takano M, Kouta H, Kikuchi R, Kita T, Miyamoto M, Watanabe A, Kato M, Goto T, Kikuchi Y: Effects of bevacizumab and pegylated liposomal doxorubicin for the patients with recurrent or refractory ovarian cancers. Gynecol Oncol 2011,122(2):233–237. 10.1016/j.ygyno.2011.04.046PubMedCrossRef Kudoh K, Takano M, Kouta H, Kikuchi R, Kita T, Miyamoto M, Watanabe A, Kato M, Goto T, Kikuchi Y: Effects of bevacizumab and pegylated liposomal doxorubicin for the patients with recurrent or refractory ovarian cancers. Gynecol Oncol 2011,122(2):233–237. 10.1016/j.ygyno.2011.04.046PubMedCrossRef
12.
go back to reference Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, Kurzeder C, du Bois A, Sehouli J, Kimmig R, Stähle A, Collinson F, Essapen S, Gourley C, Lortholary A, Selle F, Mirza MR, Leminen A, Plante M, Stark D, Qian W, Parmar MK, Oza AM: A phase 3 trial of bevacizumab in ovarian cancer; ICON 7 Investigators. N Engl J Med 2011,365(26):2484–2496. 10.1056/NEJMoa1103799PubMedCrossRef Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, Kurzeder C, du Bois A, Sehouli J, Kimmig R, Stähle A, Collinson F, Essapen S, Gourley C, Lortholary A, Selle F, Mirza MR, Leminen A, Plante M, Stark D, Qian W, Parmar MK, Oza AM: A phase 3 trial of bevacizumab in ovarian cancer; ICON 7 Investigators. N Engl J Med 2011,365(26):2484–2496. 10.1056/NEJMoa1103799PubMedCrossRef
13.
go back to reference Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, Mannel RS, Homesley HD, Fowler J, Greer BE, Boente M, Birrer MJ, Liang SX: Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 2011,365(26):2473–2483. 10.1056/NEJMoa1104390PubMedCrossRef Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, Mannel RS, Homesley HD, Fowler J, Greer BE, Boente M, Birrer MJ, Liang SX: Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 2011,365(26):2473–2483. 10.1056/NEJMoa1104390PubMedCrossRef
14.
go back to reference Aghajanian C, Finkler NJ, Rutherford T, Smith DA, Yi J, Parmar H, Nycum LR, Sovak MA: OCEANS: A randomized, double-blinded, placebo-controlled phase III trial of chemotherapy with or without bevacizumab (BEV) in patients with platinum- sensitive recurrent epithelial ovarian (EOC), primary peritoneal (PPC), or fallopian tube cancer (FTC). J Clin Oncol 2011, 29: - . suppl; abstr LBA5007 Aghajanian C, Finkler NJ, Rutherford T, Smith DA, Yi J, Parmar H, Nycum LR, Sovak MA: OCEANS: A randomized, double-blinded, placebo-controlled phase III trial of chemotherapy with or without bevacizumab (BEV) in patients with platinum- sensitive recurrent epithelial ovarian (EOC), primary peritoneal (PPC), or fallopian tube cancer (FTC). J Clin Oncol 2011, 29: - . suppl; abstr LBA5007
15.
go back to reference EMA Committee for medicinal products for human use: Summary of positive opinion Avastin, in combination with carboplatin and paclitaxel is indicated for the front-line treatment of advanced (FIGO stages III B, III C and IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer. EMA/CHMP/569545.  ,  ; 2011. EMA Committee for medicinal products for human use: Summary of positive opinion Avastin, in combination with carboplatin and paclitaxel is indicated for the front-line treatment of advanced (FIGO stages III B, III C and IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer. EMA/CHMP/569545.  ,  ; 2011.
16.
go back to reference Randall LM: Bevacizumab toxicities and their management in ovarian cancer. Gynecol Oncol 2010, 117: 497–504. 10.1016/j.ygyno.2010.02.021PubMedCrossRef Randall LM: Bevacizumab toxicities and their management in ovarian cancer. Gynecol Oncol 2010, 117: 497–504. 10.1016/j.ygyno.2010.02.021PubMedCrossRef
17.
go back to reference Cohn DE: At what cost does a potential survival advantage of bevacizumab make sense for the primary treatment of ovarian cancer? A cost-effectiveness analysis. J Clin Oncol 2011, 29: 1247–1251. 10.1200/JCO.2010.32.1075PubMedCrossRef Cohn DE: At what cost does a potential survival advantage of bevacizumab make sense for the primary treatment of ovarian cancer? A cost-effectiveness analysis. J Clin Oncol 2011, 29: 1247–1251. 10.1200/JCO.2010.32.1075PubMedCrossRef
18.
go back to reference Cobleigh MA: A phase I/II dose dose-escalation trial of bevacizumab in previously treated metastatic breast cancer. Semin Oncol 2003,30(5):Suppl 16):117–124.PubMedCrossRef Cobleigh MA: A phase I/II dose dose-escalation trial of bevacizumab in previously treated metastatic breast cancer. Semin Oncol 2003,30(5):Suppl 16):117–124.PubMedCrossRef
19.
go back to reference Dennis S: Efficacy of 1,25 mg versus 2,5 mg intravitreal bevacizumab for diabetic macular edema, Six-mounth results of a randomized controlled trial. Retina 2009,29(3):293–299. Dennis S: Efficacy of 1,25 mg versus 2,5 mg intravitreal bevacizumab for diabetic macular edema, Six-mounth results of a randomized controlled trial. Retina 2009,29(3):293–299.
20.
go back to reference Modarres M: Intravitreal injection of 2,5 mg versus 1,25 mg bevacizumab (avastin) for treatment of CNV associated with AMD. Retina 2009,29(3):319–324. 10.1097/IAE.0b013e318198148ePubMedCrossRef Modarres M: Intravitreal injection of 2,5 mg versus 1,25 mg bevacizumab (avastin) for treatment of CNV associated with AMD. Retina 2009,29(3):319–324. 10.1097/IAE.0b013e318198148ePubMedCrossRef
21.
go back to reference Kinner S, Antoch G, Bockisch A, Veit-Haibach P: Whole-bod PET/CT-colonography: a possible new concept for colorectal cancer staging. Abdom Imaging 2007,32(5):606–611. 10.1007/s00261-007-9202-8PubMedCrossRef Kinner S, Antoch G, Bockisch A, Veit-Haibach P: Whole-bod PET/CT-colonography: a possible new concept for colorectal cancer staging. Abdom Imaging 2007,32(5):606–611. 10.1007/s00261-007-9202-8PubMedCrossRef
22.
go back to reference Wahl RL, Jacene H, Kasamon Y, Lodge MA: From RECIST to PERCIST: Evolving Considerations for PET response criteria in solid tumors. J Nucl Med 2009,50(Suppl 1):122S-150S.PubMedCentralPubMedCrossRef Wahl RL, Jacene H, Kasamon Y, Lodge MA: From RECIST to PERCIST: Evolving Considerations for PET response criteria in solid tumors. J Nucl Med 2009,50(Suppl 1):122S-150S.PubMedCentralPubMedCrossRef
23.
go back to reference Peng LH: Topotecan for ovarian cancer. Cochrane Database Syst Rev 2008,16(2)):CD005589. Peng LH: Topotecan for ovarian cancer. Cochrane Database Syst Rev 2008,16(2)):CD005589.
24.
go back to reference Lorusso D: Review role of topotecan in gynecological cancers: current indications and perspectives. Crit Rev Oncol Hematol 2010,74(3):163–174. 10.1016/j.critrevonc.2009.08.001PubMedCrossRef Lorusso D: Review role of topotecan in gynecological cancers: current indications and perspectives. Crit Rev Oncol Hematol 2010,74(3):163–174. 10.1016/j.critrevonc.2009.08.001PubMedCrossRef
25.
go back to reference Bell-McGuinn K: New drugs for ovarian cancer. Ann Oncol 2011,22(suppl. 8):77–82. Bell-McGuinn K: New drugs for ovarian cancer. Ann Oncol 2011,22(suppl. 8):77–82.
26.
go back to reference Jl W: Targeting genetic and epigenetic alterations in the treatment of serous ovarian cancer. Cancer Genet 2011,204(10):525–535. 10.1016/j.cancergen.2011.09.004CrossRef Jl W: Targeting genetic and epigenetic alterations in the treatment of serous ovarian cancer. Cancer Genet 2011,204(10):525–535. 10.1016/j.cancergen.2011.09.004CrossRef
27.
go back to reference Eskander RN, Randall LM: Bevacizumab in the treatment of ovarian cancer. Biologics: targets and therapy 2011, 5: 1–5. Eskander RN, Randall LM: Bevacizumab in the treatment of ovarian cancer. Biologics: targets and therapy 2011, 5: 1–5.
28.
go back to reference Matulonis UA: Bevacizumab and its use in epithelial ovarian cancer. Futur Oncol 2011, 7: 365–379. 10.2217/fon.10.167CrossRef Matulonis UA: Bevacizumab and its use in epithelial ovarian cancer. Futur Oncol 2011, 7: 365–379. 10.2217/fon.10.167CrossRef
29.
go back to reference O'Malley DM, Richardson DL, Rheaume PS, Salani R, Eisenhauer EL, McCann GA, Fowler JM, Copeland LJ, Cohn DE, Backes FJ: Addition of bevacizumab to weekly paclitaxel significantly improves progression-free survival in heavily pretreated recurrent epithelial ovarian cancer. Gynecol Oncol 2011, 2: 269–272.CrossRef O'Malley DM, Richardson DL, Rheaume PS, Salani R, Eisenhauer EL, McCann GA, Fowler JM, Copeland LJ, Cohn DE, Backes FJ: Addition of bevacizumab to weekly paclitaxel significantly improves progression-free survival in heavily pretreated recurrent epithelial ovarian cancer. Gynecol Oncol 2011, 2: 269–272.CrossRef
30.
go back to reference Prakash P, Cronin CG, Blake MA: Role of PET/CT in ovarian cancer. AJR Am JRoentgenol 2010,194(6):W464-W470. 10.2214/AJR.09.3843CrossRef Prakash P, Cronin CG, Blake MA: Role of PET/CT in ovarian cancer. AJR Am JRoentgenol 2010,194(6):W464-W470. 10.2214/AJR.09.3843CrossRef
31.
go back to reference Schwarz JK, Grigsby PW, Dehdashti F, Delbeke D: The role of 18 F-FDG PET in assessing therapy response in cancer of the cervix and ovaries. J Nucl Med 2009,50(1):64S-73S. 10.2967/jnumed.108.057257PubMedCrossRef Schwarz JK, Grigsby PW, Dehdashti F, Delbeke D: The role of 18 F-FDG PET in assessing therapy response in cancer of the cervix and ovaries. J Nucl Med 2009,50(1):64S-73S. 10.2967/jnumed.108.057257PubMedCrossRef
32.
go back to reference Kitajima K, Murakami K, Yamasaki E, Domeki Y, Kaji Y, Morita S, Suganuma N, Sugimura K: Performance of integrated FDG-PET/contrast-enhanced CT in the diagnosis of recurrent uterine cancer: comparison with PET and enhanced CT. Eur J Nucl Med Mol Imaging 2009,36(3):362–372. 10.1007/s00259-008-0956-1PubMedCrossRef Kitajima K, Murakami K, Yamasaki E, Domeki Y, Kaji Y, Morita S, Suganuma N, Sugimura K: Performance of integrated FDG-PET/contrast-enhanced CT in the diagnosis of recurrent uterine cancer: comparison with PET and enhanced CT. Eur J Nucl Med Mol Imaging 2009,36(3):362–372. 10.1007/s00259-008-0956-1PubMedCrossRef
33.
go back to reference Kitajima K, Murakami K, Yamasaki E, Domeki Y, Kaji Y, Morita S, Suganuma N, Sugimura K: Diagnostic accuracy of integrated FDG-PET/contrast-enhanced CT in staging ovariancancer: comparison with enhanced CT. Eur J Nucl Med Mol Imaging 2008,35(10):1912–1920. 10.1007/s00259-008-0890-2PubMedCrossRef Kitajima K, Murakami K, Yamasaki E, Domeki Y, Kaji Y, Morita S, Suganuma N, Sugimura K: Diagnostic accuracy of integrated FDG-PET/contrast-enhanced CT in staging ovariancancer: comparison with enhanced CT. Eur J Nucl Med Mol Imaging 2008,35(10):1912–1920. 10.1007/s00259-008-0890-2PubMedCrossRef
34.
go back to reference Piccardo A, Biscaldi E, DeCensi A, Bianchi P, Altrinetti V, Barbera F, Cabria M, D'Amico M, Rollandi GA, Villavecchia G: Integrated contrast enhanced 18F-FDG-PET/CTcolonography in reccurent ovarian cancer. Eur J Nucl Med Mol I 2010, 37: 2. Piccardo A, Biscaldi E, DeCensi A, Bianchi P, Altrinetti V, Barbera F, Cabria M, D'Amico M, Rollandi GA, Villavecchia G: Integrated contrast enhanced 18F-FDG-PET/CTcolonography in reccurent ovarian cancer. Eur J Nucl Med Mol I 2010, 37: 2.
35.
go back to reference Piccardo A, Biscaldi E, DeCensi A, Bianchi P, Altrinetti V, Barbera F, Cabria M, D'Amico M, Rollandi GA, Villavecchia G: Integrated contrast enhanced 18F-FDG-PET/CT-colonography: a useful diagnostic tool to improve detection of peritoneal metastases in ovarian cancer. Q J Nucl Med Mol Im 2011, 55: 1. Piccardo A, Biscaldi E, DeCensi A, Bianchi P, Altrinetti V, Barbera F, Cabria M, D'Amico M, Rollandi GA, Villavecchia G: Integrated contrast enhanced 18F-FDG-PET/CT-colonography: a useful diagnostic tool to improve detection of peritoneal metastases in ovarian cancer. Q J Nucl Med Mol Im 2011, 55: 1.
Metadata
Title
A case series of low dose bevacizumab and chemotherapy in heavily pretreated patients with epithelial ovarian cancer
Authors
Carlotta Defferrari
Sara Campora
Mauro D'Amico
Arnoldo Piccardo
Ennio Biscaldi
Daniela Rosselli
Ambra Pasa
Matteo Puntoni
Alberto Gozza
Alessandra Gennari
Silvia Zanardi
Rita Lionetto
Michela Bandelloni
Andrea DeCensi
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2012
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/1757-2215-5-17

Other articles of this Issue 1/2012

Journal of Ovarian Research 1/2012 Go to the issue