Radioimunoterapia: uma abordagem terapêutica promissora no tratamento do carcinoma do ovário
DOI:
https://doi.org/10.25758/set.1244Palavras-chave:
Carcinoma epitelial do ovário, Anticorpos monoclonais, Radioimunoterapia, Antigénios, Marcadores tumoraisResumo
O cancro do ovário é a neoplasia ginecológica com maior índice de mortalidade entre a população do sexo feminino apesar dos consideráveis progressos verificados no seu tratamento. Caso o diagnóstico seja precoce, a taxa de sobrevida é bastante elevada, mas o cancro do ovário primário é assintomático e na maioria das vezes só é diagnosticado numa fase avançada da doença, resultando num prognóstico pouco favorável. A falta de especificidade das modalidades terapêuticas associada à heterogeneidade das células oncológicas tem limitado a terapia do cancro do ovário. Alguns dos avanços clínicos mais promissores no tratamento do cancro são as terapêuticas dirigidas a alvos específicos, especialmente proteínas sobre expressas em vários tipos de células epiteliais. Neste contexto, a radioimunoterapia com anticorpos monoclonais tem sido explorada nos carcinomas epiteliais que constituem cerca de 90% das neoplasias do ovário. Esta estratégia terapêutica, que tira partido da ação combinada da radiotoxicidade associada aos radionuclídeos para terapia e dos efeitos citotóxicos do anticorpo, pode constituir uma alternativa às terapias convencionais, potenciando a eficácia do tratamento. Neste artigo são abordados aspetos relacionados com o cancro do ovário, nomeadamente o seu diagnóstico e terapia. São ainda revistos, de forma breve, alguns estudos clínicos em que a eficácia de anticorpos monoclonais marcados com radionuclídeos para terapêutica foi avaliada no cancro do ovário.
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Referências
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359-86.
Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013 [cited 2015 Sep 2]. Available from: http://globocan.iarc.fr
Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013;49(6):1374-403.
Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, editors.Harrison’s principles of internal medicine. 18thed. New York: McGraw-Hill; 2012. ISBN 9780071748896
Hennessy BT, Coleman RL, Markman M. Ovarian cancer. Lancet. 2009;374(9698):1371-82.
Oliveira CF, editor. Manual de ginecologia (vol. II). Lisboa: Permayer Portugal; 2009. ISBN9789727332540
Prat J, FIGO Committee on Gynecologic Oncology. Staging classification for cancer of the ovary, fallopian tube and peritoneum. Int J Gynaecol Obstet. 2014;124(1):1-5.
Bast RC Jr, Badgwell D, Lu Z, Marquez R, Rosen D, Liu J, et al. New tumor markers: CA125 and beyond. Int J Gynecol Cancer. 2005;15Suppl 3:274-81.
Gu P, Pan LL, Wu SQ, Sun L, Huang G. CA 125, PET alone, PET-CT, CT and MRI in diagnosing recurrent ovarian carcinoma: a systematic review and meta-analysis. Eur J Radiol. 2009;71(1):164-74.
Canevari S, Gariboldi M, Reid JF, Bongarzone I, Pierotti MA. Molecular predictors of response and outcome in ovarian cancer. Crit Rev OncolHematol. 2006;60(1):19-37.
Giuntoli RL 2nd, Rodriguez GC, Whitaker RS, Dodge R, Voynow JA. Mucin gene expression in ovarian cancers. Cancer Res. 1998;58(23):5546-50.
Thor A, Gorstein F, Ohuchi N, Szpak CA, Johnston WW, Schlom J. Tumor-associated glycoprotein (TAG-72) in ovarian carcinomas defined by monoclonal antibody B72.3. J Natl Cancer Inst. 1986;76(6):995-1006.
Rosen DG, Wang L, Atkinson JN, Yu Y, Lu KH, Diamandis EP, et al. Potential markers that complement expression of CA125 in epithelial ovarian cancer. GynecolOncol. 2005;99(2):267-77.
Rustin GJ, Marples M, Nelstrop AE, Mahmoudi M, Meyer T. Use of CA-125 to define progression of ovarian cancer in patients with persistently elevated levels. J ClinOncol. 2001;19(20):4054-7.
Sociedade Portuguesa de Ginecologia. Cancro ginecológico: consensos nacionais 2013 [Internet]. Coimbra: 2012 Nov 24 [cited 2015 Aug 21]. Available from: http://www.spginecologia.pt/uploads/livro-cancro-Ginecol-gico-com-logo_set13.pdf
Ledermann JA, Raja FA, Fotopoulou C, Gonzalez-Martin A, Colombo N, Sessa C, et al. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. AnnOncol. 2013;24Suppl 6:vi24-32.
Iyer VR, Lee SI. MRI, CT, and PET/CT for ovarian cancer detection and adnexal lesion characterization. AJR Am J Roentgenol. 2010;194(2):311-21.
Rieber A, Nüssle K, Stöhr I, Grab D, Fenchel S, Kreienberg R, et al.Preoperative diagnosis of ovarian tumors with MR imaging: comparison with transvaginal sonography, positron emission tomography, and histologic findings. AJR Am J Roentgenol.2001;177(1):123-9.
Yoshida Y, Kurokawa T, Kawahara K, Tsuchida T, Okazawa H, Fujibayashi Y, et al. Incremental benefits of FDG positron emission tomography over CT alone for the preoperative staging of ovarian cancer. AJR Am J Roentgenol. 2004;182(1):227-33.
Sebastian S, Lee SI, Horowitz NS, Scott JA, Fischman AJ, Simeone JF, et al. PET-CT vs. CT alone in ovarian cancer recurrence. Abdom Imaging. 2008;33(1):112-8.
Hauth EA, Antoch G, Stattaus J, Kuehl H, Veit P, Bockisch A, et al. Evaluation of integrated whole-body PET/CT in the detection of recurrent ovarian cancer. Eur J Radiol. 2005;56(2):263-8.
Berek JS, Hacker NF. Practical gynecologic oncology. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2000. ISBN 9780683307191
Lambert HE, Rustin GJ, Gregory WM, Nelstrop AE. A randomized trial comparing single-agent carboplatin with carboplatin followed by radiotherapy for advanced ovarian cancer: a North Thames Ovary Group study. J Clin Oncol. 1993;11(3):440-8.
Harries M, Gore M. Part I: Chemotherapy for epithelial ovarian cancer–treatment at first diagnosis. Lancet Oncol. 2002;3(9):529-36.
Howell SB, Zimm S, Markman M, Abramson IS, Cleary S, Lucas WE, et al. Long-term survival of advanced refractory ovarian carcinoma patients with small-volume disease treated with intraperitoneal chemotherapy. J Clin Oncol. 1987;5(10):1607-12.
Rothenberg ML, Liu PY, Braly PS, Wilczynski SP, Hannigan EV, Wadler S, et al. Combined intraperitoneal and intravenous chemotherapy for women with optimally debulked ovarian cancer: results from an intergroup phase II trial. J Clin Oncol. 2003;21(7):1313-9.
Yap TA, Carden CP Kaye SB. Beyond chemotherapy: targeted therapies in ovarian cancer. Nat Rev Cancer. 2009;9(3):167-81.
Ledermann JA, Perren T, Raja FA, Embleton AC, Rustin GJ, Jayson G, et al. Randomised double-blind phase III trial of cediranib (AZD 2171) in relapsed platinum sensitive ovarian cancer: results of the ICON6 trial. In 10th NCRI Cancer Conference, Liverpool (UK), 2-5 November 2014.
duBois A, Floquet A, Kim JW, Rau J, Del Campo JM, Friedlander M. et al. Randomized, double-blind, phase III trial of pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (AEOC): results of an international Intergroup trial (AGO-OVAR16). J Clin Oncol. 2013;31(Suppl):abstr LBA5503.
Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011;365(26):2484-96.
Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365(26):2473-83.
Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: the AURELIA open-label randomized phase III trial. J Clin Oncol. 2014;32(13):1302-8.
Koppe MJ, Postema EJ, Aarts F, Oyen WJ, Bleichrodt RP, Boerman OC. Antibody-guided radiation therapy of cancer. Cancer Metastasis Rev. 2005;24(4):539-67.
Mansi L, Kitson SL, Cuccurullo V, Ciarmiello A. Basic premises to molecular imaging and radionuclide therapy – Part 1. J Diagn Imaging Ther. 2014;1(1):137-56.
Macey DJ, Meredith RF. A strategy to reduce red marrow dose for intraperitoneal radioimmunotherapy. Clin Cancer Res. 1999;5(10 Suppl):3044s-7s.
Taylor-Papadimitriou J, Peterson JA, Arklie J, Burchell J, Ceriani RL, Bodmer WF. Monoclonal antibodies to epithelium-specific components of the human milk fat globule membrane: production and reaction with cells in culture. Int J Cancer. 1981;28(1):17-21.
Epenetos AA, Munro AJ, Stewart S, Rampling R, Lambert HE, McKenzie CG, et al. Antibody-guided irradiation of advanced ovarian cancer with intraperitoneally administered radiolabeled monoclonal antibodies. J Clin Oncol. 1987;5(12):1890-9.
Hird V, Maraveyas A, Snook D, Dhokia B, Soutter WP, Meares C, et al. Adjuvant therapy of ovarian cancer with radioactive monoclonal antibody. Br J Cancer. 1993;68(2):403-6.
Stewart JS, Hird V, Snook D, Dhokia B, Sivolapenko G, Hooker G, et al. Intraperitoneal yttrium-90-labeled monoclonal antibody in ovarian cancer. J Clin Oncol. 1990;8(12):1941-50.
Maraveyas A, Snook D, Hird V, Kosmas C, Meares CF, Lambert HE, et al. Pharmacokinetics and toxicity of an yttrium-90-CITC-DTPA-HMFG1 radioimmunoconjugate for intraperitoneal radioimmunotherapy of ovarian cancer. Cancer. 1994;73(3 Suppl):1067-75.
Nicholson S, Gooden CS, Hird V, Maraveyas A, Mason P, Lambert HE, et al. Radioimmunotherapy after chemotherapy compared to chemotherapy alone in the treatment of advanced ovarian cancer: a matched analysis. Oncol Rep. 1998;5(1):223-6.
Epenetos AA, Hird V, Lambert H, Mason P, Coulter C. Long-term survival of patients with advanced ovarian cancer treated with intraperitoneal radioimmunotherapy. Int J Gynecol Cancer. 2000;10(1 Suppl):44-6.
Nicholson S, Bell S, McCormack M, Bomphray CC, Ganesan T, Gore ME, et al. A randomised phase III trial of adjuvant intraperitoneal radioimmunotherapy in ovarian cancer. In 2000 ASCO Ann Meeting Proc. 2000:abstr 1514.
Clark A. PhD study costs Antisoma £44m. The Guardian. 2000 May 23. Available from: http://www.theguardian.com/business/2000/may/23/7
Verheijen RH, Massuger LF, Benigno BB, Epenetos AA, Lopes A, Soper JT, et al. Phase III trial of intraperitoneal therapy with yttrium-90-labeled HMFG1 murine monoclonal antibody in patients with epithelial ovarian cancer after a surgically defined complete remission. J Clin Oncol. 2006;24(4):571-8.
Oei AL, Verheijen RH, Seiden MV, Benigno BB, Lopes A, Soper JT, et al. Decreased intraperitoneal disease recurrence in epithelial ovarian cancer patients receiving intraperitoneal consolidation treatment with yttrium-90-labeled murine HMFG1 without improvement in overall survival. Int J Cancer. 2007;120(12):2710-4.
Muto MG, Finkler NJ, Kassis AI, Howes AE, Anderson LL, Lau CC, et al. Intraperitoneal radioimmunotherapy of refractory ovarian carcinoma utilizing iodine-131-labeled monoclonal antibody OC125. Gynecol Oncol. 1992;45(3):265-72.
Mahé MA, Fumoleau P, Fabbro M, Guastalla JP, Faurous P, Chauvot P, et al. A phase II study of intraperitoneal radioimmunotherapy with iodine-131-labeled monoclonal antibody OC-125 in patients with residual ovarian carcinoma. Clin Cancer Res. 1999;5(10 Suppl):3249s-53s.
Rosenblum MG, Verschraegen CF, Murray JL, Kudelka AP, Gano J, Cheung L, et al. Phase I study of 90Y-labeled B72.3 intraperitoneal administration in patients with ovarian cancer: effect of dose and EDTA coadministration on pharmacokinetics and toxicity. Clin Cancer Res. 1999;5(5):953-61.
Meredith RF, Partridge EE, Alvarez RD, Khazaeli MB, Plott G, Russell CD, et al. Intraperitoneal radioimmunotherapy of ovarian cancer with lutetium-177-CC49. J Nucl Med. 1996;37(9):1491-6.
Alvarez RD, Partridge EE, Khazaeli MB, Plott G, Austin M, Kilgore L, et al. Intraperitoneal radioimmunotherapy of ovarian cancer with 177Lu-CC49: a phase I/II study. Gynecol Oncol. 1997;65(1):94-101.
Meredith RF, Alvarez RD, Partridge EE, Khazaeli MB, Lin CY, Austin JM, et al. Intraperitoneal radioimmunochemotherapy of ovarian cancer: a phase I study. Cancer Biother Radiopharm. 2001;16(4):305-15.
Steren A, Sevin BU, Perras J, Angioli R, Nguyen H, Guerra L, et al. Taxol sensitizes human ovarian cancer cells to radiation. Gynecol Oncol. 1993;48(2):252-8.
Roselli M, Guadagni F, Buonomo O, Belardi A, Vittorini V, Mariani-Costantini R, et al. Systemic administration of recombinant interferon alfa in carcinoma patients upregulates the expression of the carcinoma-associated antigens tumor-associated glycoprotein-72 and carcinoembryonic antigen. J Clin Oncol. 1996;14(7):2031-42.
Alvarez RD, Huh WK, Khazaeli MB, Meredith RF, Partridge EE, Kilgore LC, et al. Phase I study of combined modality (90)Yttrium-CC49 intraperitoneal radioimmunotherapy for ovarian cancer. Clin Cancer Res. 2002;8(9):2806-11.
Campbell IG, Jones TA, Foulkes WD, Trowsdale J. Folate-binding protein is a marker for ovarian cancer. Cancer Res. 1991;51(19):5329-38.
Molthoff CF, Buist MR, Kenemans P, Pinedo HM. Boven E. Experimental and clinical analysis of the characteristics of a chimeric monoclonal antibody, MOv18, reactive with an ovarian cancer-associated antigen. J Nucl Med. 1992;33(11):2000-5.
Crippa F, Bolis G, Seregni E, Gavoni N, Scarfone G, Ferraris C, et al. Single-dose intraperitoneal radioimmunotherapy with the murine monoclonal antibody I-131 MOv18: clinical results in patients with minimal residual disease of ovarian cancer. Eur J Cancer. 1995;31A(5):686-90.
Andersson H, Lindegren S, Bäck T, Jacobsson L, Leser G, Horvath G. The curative and palliative potential of the monoclonal antibody MOv18 labelled with 211At in nude mice with intraperitoneally growing ovarian cancer xenografts: a long-term study. Acta Oncol. 2000;39(6):741-5.
Andersson H, Lindegren S, Bäck T, Jacobsson L, Leser G, Horvath G. Radioimmunotherapy of nude mice with intraperitoneally growing ovarian cancer xenograft utilizing 211At-labelled monoclonal antibody MOv18. Anticancer Res. 2000;20(1A):459-62.
Andersson H, Palm S, Lindegren S, Bäck T, Jacobsson L, Leser G, et al. Comparison of the therapeutic efficacy of 211At- and 131I-labelled monoclonal antibody MOv18 in nude mice with intraperitoneal growth of human ovarian cancer. Anticancer Res. 2001;21(1A):409-12.
Mattes MJ, Look K, Furukawa K, Pierce VK, Old LJ, Lewis JL Jr, et al. Mouse monoclonal antibodies to human epithelial differentiation antigens expressed on the surface of ovarian carcinoma ascites cells. Cancer Res. 1987;47(24 Pt 1):6741-50.
Yin BW, Kiyamova R, Chua R, Caballero OL, Gout I, Gryshkova V, et al. Monoclonal antibody MX35 detects the membrane transporter NaPi2b (SLC34A2) in human carcinomas. Cancer Immun. 2008;8:3.
Finstad CL, Lloyd KO, Federici MG, Divgi C, Venkatraman E, Barakat RR, et al. Distribution of radiolabeled monoclonal antibody MX35 F(ab’)2 in tissue samples by storage phosphor screen image analysis: evaluation of antibody localization to micrometastatic disease in epithelial ovarian cancer. Clin Cancer Res. 1997;3(8):1433-42.
Rubin SC, Kostakoglu L, Divgi C, Frederici MG, Finstad CL, Lloyd KO, et al. Biodistribution and intraoperative evaluation of radiolabeled monoclonal antibody MX35 in patients with epithelial ovarian cancer. Gynecol Oncol. 1993;51(1):61-6.
Elgqvist J, Andersson H, Bäck T, Hultborn R, Jensen H, Karlsson B, et al. Therapeutic efficacy and tumor dose estimations in radioimmunotherapy of intraperitoneally growing OVCAR-3 cells in nude mice with 211At-labeled monoclonal antibody MX35. J Nucl Med. 2005;46(11):1907-15.
Elgqvist J, Andersson H, Bäck T, Claesson I, Hultborn R, Jensen H, et al. α-radioimmunotherapy of intraperitoneally growing OVCAR-3 tumors of variable dimensions: outcome related to measured tumor size and mean absorbed dose. J Nucl Med. 2006;47(8):1342-50.
Andersson H, Cederkrantz E, Bäck T, Divgi C, Elgqvist J, Himmelman J, et al. Intraperitoneal alpha-particle radioimmunotherapy of ovarian cancer patients: pharmacokinetics and dosimetry of (211)At-MX35 F(ab’)2: a phase I study. J Nucl Med. 2009;50(7):1153-60.
Teplinsky E, Muggia F. Targeting HER2 in ovarian and uterine cancers: challenges and future directions. Gynecol Oncol. 2014;135(2):364-70.
Milenic DE, Brady ED, Garmestani K, Albert PS, Abdulla A, Brechbiel MW. Improved efficacy of alpha-particle-targeted radiation therapy: dual targeting of human epidermal growth factor receptor-2 and tumor-associated glycoprotein 72. Cancer. 2010;116(4 Suppl):1059-66.
Milenic DE, Baidoo KE, Shih JH, Wong KJ, Brechbiel MW. Evaluation of platinum chemotherapy in combination with HER2-targeted a-particle radiation. Cancer Biother Radiopharm. 2013;28(6):441-9.
Meredith RF, Torgue J, Azure MT, Shen S, Saddekni S, Banaga E, et al. Pharmacokinetics and imaging of 212Pb-TCMC-trastuzumab after intraperitoneal administration in ovarian cancer patients. Cancer Biother Radiopharm. 2014;29(1):12-7.
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