Article Data

  • Views 268
  • Dowloads 144

Original Research

Open Access

Bevacizumab for the treatment of recurrent ovarian cancer: a retrospective cohort study

  • S. N. Akers1
  • G. Riebandt2
  • 'A. Miller3
  • A. Groman3
  • K. Odunsi1,*,
  • S. Lele1

1,Division of Gynecologic Oncology

2,Department of Pharmacy

3Department of Biostatistics Roswell Park Cancer Institute, Buffalo, NY (USA).

DOI: 10.12892/ejgo340201 Vol.34,Issue 2,March 2013 pp.113-119

Published: 24 March 2013

*Corresponding Author(s): K. Odunsi E-mail: kunle.odnsi@roswellpark.org

Abstract

Objective: To determine response rates (RR), progression-free survival (PFS), overall survival (OS), and toxicity in patients treated with cytotoxic chemotherapy, in combination with bevacizumab compared to cytotoxic chemotherapy alone, in the setting of recurrent ovarian cancer. Materials and Methods: After obtaining Institutional Review Board approval, two cohorts of patients with recurrent ovarian cancer were identified: 1) patients that received cytotoxic chemotherapy with bevacizumab from January 2006 to June 2009; 2) patients that received cytotoxic chemotherapy alone. RR were measured using RECIST criteria or by CA-125 levels using modified Rustin criteria. RR, OS, and PFS were determined using Kaplan-Meier survival analysis. Results: Thirty-two patients that received bevacizumab in combination with cytotoxic chemotherapy and 32 patients that received cytotoxic chemotherapy alone were identified. The control patients were matched for age, platinum response, histology, surgical outcome, grade, and number of previous chemotherapy regimens. There were no differences between the two cohorts in the rates of venous thromboembolism (VTE) (p = 0.39), bleeding (p = 0.15) or bowel obstruction (p = 0.40). The rate of hypertension in the bevacizumab cohort was greater than in the comparison cohort (p < 0.005). There were no differences in response rates PR/CR vs SD/PD (p = 0.46), OS (p = 0.79) or PFS (p = 0.43). Conclusions: With increased toxicity, increased cost of therapy and no improvement in PFS or OS, the role of bevacizumab in patients with recurrent ovarian cancer warrants further investigation.

Keywords

Squamous cell carcinoma; Endometrial carcinoma; Ichthyosis uteri; Ovarian cancer; Chemotherapy; Bevacizumab.

Cite and Share

S. N. Akers,G. Riebandt,'A. Miller,A. Groman,K. Odunsi,S. Lele. Bevacizumab for the treatment of recurrent ovarian cancer: a retrospective cohort study. European Journal of Gynaecological Oncology. 2013. 34(2);113-119.

References

[1] Jemal A., Siegel R., Xu J., Ward E.: “Cancer statistics, 2010”. CA Cancer J. Clin., 2010, 60, p. 277.

[2] Young R.C. Decker D.G., Wharton J.T., Piver M.S., Sindelar W.F. Edwards B.K. et al.: “Staging laparotomy in early ovarian cancer”. JAMA, 1983, 250, 3072.

[3] Hurt J.D., Richardson D.L., Seamon L.G., Fowler J.F., Copeland L.J., Cohn D.E. et al.: “Sustained progression-free survival with weekly paclitaxel and bevacizumab in recurrent ovarian cancer”. Gynecol. Oncol., 2009, 115, 396.

[4] Markman M.: “Antineoplastic agents in the management of ovarian cancer: current status and emerging therapeutic strategies”. Trends Pharmacol. Sci., 2008, 29, 515.

[5] Stone R.L., Sood A.K., Coleman R.L.: “Collateral damage: toxic effects of targeted antiangiogenic therapies in ovarian cancer”. Lancet Oncol., 2010, 11, 465.

[6] Santin A.D., Hermonat P.L., Ravaggi A., Cannon M.J., Pecorelli S., Parham G.P.: “Secretion of vascular endothelial growth factor in ovarian cancer”. Eur. J. Gynaecol. Oncol., 1999, 20, 177.

[7] Penson R.T., Dizon D.S., Cannistra S.A., Roche M.R., Krasner C.N., Berlin S.T. et al.: “Phase II study of carboplatin, paclitaxel, and bevacizumab with maintenance bevacizumab as first-line chemotherapy for advanced mullerian tumors”. J. Clin. Oncol., 2010, 28, 154.

[8] Alvarez A.A., Krigman H.R., Whitaker R.S., Dodge R.K., Rodriguez G.C.: “The prognostic significance of angiogenesis in epithelial ovarian carcinoma”. Clin. Cancer Res., 1999, 5, 587.

[9] Gasparini G., Weidner N., Bevilacqua P., Maluta S., Dalla Palma P., Caffo O. et al.: “Tumor microvessel density, p53 expression, tumor size, and peritumoral lymphatic vessel invasion are relevant prognostic markers in node-negative breast carcinoma”. J. Clin. Oncol., 1994, 12, 454.

[10] Hollingsworth H.C., Kohn E.C., Steinberg S.M., Rothenberg M.L., Merino M.J.: “Tumor angiogenesis in advanced stage ovarian carcinoma”. Am. J. Pathol., 1995, 147, 33.

[11] Nakanishi Y., Kodama J., Yoshinouchi M., Tokumo K., Kamimura S., Okuda H. et al.: “The expression of vascular endothelial growth factor and transforming growth factor-beta associates with angiogenesis in epithelial ovarian cancer”. Int. J. Gynecol. Pathol., 1997, 16, 256.

[12] Paley P.J., Staskus K.A., Gebhard K., Mohanraj D., Twiggs L.B., Carson L.F. et al.: “Vascular endothelial growth factor expression in early stage ovarian carcinoma”. Cancer, 1997, 80, 98.

[13] Cooper B.C., Ritchie J.M., Broghammer C.L., Coffin J., Sorosky J.K., Buller R.E. et al.: “Preoperative serum vascular endothelial growth factor levels: significance in ovarian cancer”. Clin. Cancer Res., 2002, 8, 3193.

[14] Dvorak H.F.: “Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy”. J. Clin. Oncol., 2002, 20, 4368.

[15] Ferrara N.: “Molecular and biological properties of vascular endothelial growth factor”. J. Mol. Med., 1999, 77, 527

[16] Yoneda J., Kuniyasu H., Crispens M.A., Price J.E., Bucana C.D., Fidler I.J.: “Expression of angiogenesis-related genes and progression of human ovarian carcinomas in nude mice”. J. Natl. Cancer Inst., 1998, 90, 447.

[17] Richardson D.L., Backes F.J., Seamon L.G., Zanagnolo V., O’Malley D.M., Cohn D.E. et al.: “Combination gemcitabine, platinum, and bevacizumab for the treatment of recurrent ovarian cancer”. Gynecol. Oncol., 2008, 111, 461.

[18] Cannistra S.A., Matulonis U.A., Penson R.T., Hambleton J., Dupont J., Mackey H. et al.: “Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer”. J. Clin. Oncol., 2007, 25, 5180.

[19] Cohn D.E., Valmadre S., Resnick K.E., Eaton L.A., Copeland L.J., Fowler J.M.: “Bevacizumab and weekly taxane chemotherapy demonstrates activity in refractory ovarian cancer”. Gynecol. Oncol., 2006, 102, 134.

[20] Sfakianos G.P., Numnum T.M., Halverson C.B., Panjeti D., Kendrick J.Et., Straughn J.M. Jr.: “The risk of gastrointestinal perforation and/or fistula in patients with recurrent ovarian cancer receiving bevacizumab compared to standard chemotherapy: a retrospective cohort study”. Gynecol. Oncol., 2009, 114, 424.

[21] Cohen M.H. Gootenberg J., Keegan P., Pazdur R.: “FDA drug approval summary: bevacizumab (Avastin) plus Carboplatin and Paclitaxel as first-line treatment of advanced/metastatic recurrent nonsquamous non-small cell lung cancer”. Oncologist, 2007, 12, 713.

[22] Kabbinavar F., Hurwitz H.I., Fehrenbacher L., Meropol N.J., Novotny W.F., Lieberman G. et al.: “Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer”. J. Clin. Oncol., 2003, 21, 60.

[23] Miller K., Wang M., Gralow J., Dickler M., Cobleigh M., Perez E.A. et al.: “Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer”. N. Engl. J. Med., 2007, 357, 2666.

[24] Sandler A., Gray R., Perry M.C., Brahmer J., Schiller J.H., Dowlati A. et al.: “Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer”. N. Engl. J. Med., 2006, 355, 2542.

[25] Yang J.C. Haworth L., Sherry R.M., Hwu P., Schwartzentruber D.J., Topalian S.L. et al.: “A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer”. N. Engl. J. Med., 2003, 349, 427.

[26] Burger R.A. Sill M.W., Monk B.J., Greer B.E., Sorosky J.I.: Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group Study”. J. Clin. Oncol., 2007, 25, 5165.

[27] Garcia, A.A., Hirte H., Fleming G., Yang D., Tsao-Wei D.D., Roman L. et al.: “Phase II clinical trial of bevacizumab and lowdose 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, 76.

[28] Wright J.D. Secord A.A., Numnum T.M., Rocconi R.P., Powell M.A., Berchuck A. et al.: “A multi-institutional evaluation of factors predictive of toxicity and efficacy of bevacizumab for recurrent ovarian cancer”. Int. J. Gynecol. Cancer, 2008, 18, 400.

[29] Burger R., Brady M., Bookman M., Walker J., Homesley H., Fowler J. et al.: “Phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC): A Gynecologic Oncology Group study”. J. Clin. Oncol., 2010, 28, 18s.

[30] Pfisterer J., Perren T., Smart A.M., Ledermann J., Selle F., Kristensen G., et al.: “On behalf of ICON7 GCIG collaborators. A randomised controlled trial of bevacizumab in women with newly diagnosed epithelial ovarian, primary peritoneal or fallopian tube cancer”. Int. J. Gynecol. Oncol., 2010, 20, 2.

[31] Perren T., Swart A.M., Pfisterer J., Ledermann J., Lortholary A., Kristensen G. et al.: “On behalf of GCIG ICON7 collaborators. A phase III randomized gynecologic cancer intergroup trial of concurrent bevacizumab and chemotherapy followed by maintenance bevacizumab, versus chemotherapy alone in women with newly diagnosed epithelial ovarian (EOC), primary peritoneal (PPC), or fallopian tube cancer (FTC)”. ESMO, 2010, Abstract LBA4.

[32] Burger R.A., Brady M.F., Bookman M.A. et al.: “Phase II trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC) or fallopian tube cancer (FTC): A Gynecologic Oncology Group study”. J. Clin. Oncol., 2010, 28, 5s.

[33] Aghajanian C., Finkler N., Rutherford T., Smith D., Yi J., Parmar H. et al.: “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, LBA5007.

[34] Randall L.M., Monk B.J.: “Bevacizumab toxicities and their management in ovarian cancer”. Gynecol. Oncol., 2010, 117, 497.

[35] Therasse P., Arbuck S.G., Eisenhauer E.A., Wanders J., Kaplan R.S., Rubinstein L. et al.: “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., 2000, 92, 205.

[36] Guppy A.E., Rustin G.J.: “CA125 response: can it replace the traditional response criteria in ovarian cancer”. Oncologist, 2002, 7, 437.

[37] Nimeiri H.S., Oza A.M., Morgan R.J., Friberg G., Kasza K., Faoro L. et al.: “Efficacy and safety of bevacizumab plus erlotinib for patients with recurrent ovarian, primary peritoneal, and fallopian tube cancer: a trial of the Chicago, PMH, and California Phase II Consortia”. Gynecol. Oncol., 2008, 110, 49.

[38] McGonigle K.F., Muntz H.G., Vuky J.L., Paley P.J., VD S., Gray H.J. et al.: “Phase II prospective study of weekly topotecan and bevacizumab in platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer”. Gynecol. Oncol., 2009, 112, 145.

[39] Loizzi V., Cormio G., Resta L., Rossi C.A., Di Gilio A.R., Cuccovillo A. et al.: “Neoadjuvant chemotherapy in advanced ovarian cancer: a case-control study”. Int. J. Gynecol. Cancer, 2005, 15, 217.

[40] Allegra C.J., Yothers G., O’Connell M.J., Sharif S., Colangelo L.H., Lopa S.H. et al.: “Initial safety report of NSABP C-08: A randomized phase III study of modified FOLFOX6 with or without bevacizumab for the adjuvant treatment of patients with stage II or III colon cancer”. J. Clin. Oncol., 2009, 27, 3385.

[41] Escudier B., Pluzanska A., Koralewski P., Ravaud A., Bracarda S., Szczylik C. et al.: “Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, doubleblind phase III trial”. Lancet, 2007, 370, 2103.

[42] Giantonio B.J., Catalano P.J., Meropol N.J., O’Dwyer P.J., Mitchell E.P., Alberts S.R. et al.: “Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200”. J. Clin. Oncol., 2007, 25, 1539.

[43] Hurwitz H., Fehrenbacher L., Novotny W., Cartwright T., Hainsworth J., Heim W. et al.: “Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer”. N. Engl. J. Med., 2004, 350, 2335.

[44] Miller K.D., Chap L.I., Holmes F.A., Cobleigh M.A., Marcom P.K., Fehrenbacher L. et al.: “Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer”. J. Clin. Oncol., 2005, 23, 792.

[45] Reck M., von Pavel J., Zatloukal P., Ramlau R., Gorbounova V., Hirsh V. et al.: “Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil”. J. Clin. Oncol., 2009, 27, 1227.

[46] Saltz L.B. Clarke S., Diaz-Rubio E., Scheithauer W., Figer A., Wong R. et al.: “Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study”. J. Clin. Oncol., 2008, 26, 2013.

[47] Burger R.A., Brady M.F., Bookman M.A., Fleming G.F., Monk B.J., Huang H. et al.: “Incorporation of bevacizumab in the primary treatment of ovarian cancer”. N. Engl. J. Med., 2011, 365, 2473.

Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.

Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.

JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.

Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.

BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Submission Turnaround Time

Conferences

Top