RESUMO
Serous surface papillary borderline ovarian tumors (SSPBOTs) are a rare morphologic variant of serous ovarian tumors that are typically confined to the ovarian surface, while the ovaries themselves tend to appear normal in size and shape. In this report, we describe the findings from five premenopausal women diagnosed with SSPBOTs, in whom ultrasound showed grossly normal ovaries that were partially or wholly covered with irregular solid tumors. In all five cases, histologic examination showed evidence of borderline serous tumors. These findings demonstrate that SSPBOTs can be diagnosed on a preoperative sonographic examination, which could facilitate conservative, fertility-sparing surgery in young women affected by this condition.
Assuntos
Adenocarcinoma Papilar/diagnóstico por imagem , Neoplasias Císticas, Mucinosas e Serosas/diagnóstico por imagem , Neoplasias Ovarianas/diagnóstico por imagem , Adenocarcinoma Papilar/cirurgia , Adulto , Feminino , Humanos , Neoplasias Císticas, Mucinosas e Serosas/cirurgia , Neoplasias Ovarianas/cirurgia , Ovário/diagnóstico por imagem , Ovário/cirurgia , Reprodutibilidade dos Testes , UltrassonografiaRESUMO
IMPORTANCE OF THE FIELD: Ovarian cancer has the highest mortality of all female reproductive tract cancers, which reflects both the absence of proven ovarian cancer screening tests and the development of drug-resistant cancer cell. Apart from varying the dosages, schedules, mode of delivery and combinations of existing drugs, efforts must continue to identify signaling pathways in tumor cells sufficiently different from normal cells that can be a target for maximizing tumor kill and minimizing toxicity. AREAS COVERED IN THIS REVIEW: Some of the most important cellular pathways are analyzed and discussed and the most interesting clinical trials, both closed and ongoing, described. WHAT THE READER WILL GAIN: The reader will gain a panoramic vision of all the most active drugs in clinical investigations in ovarian cancer. The reader will also better understand what the unresolved problems of molecular research are and how complicated the process 'from the bench to the bedside' is. TAKE HOME MESSAGE: It is only with a strong commitment, cooperation and collaboration from the international ovarian cancer community that significant improvement in patient outcomes can be attained beyond the marginal gains achieved so far.
Assuntos
Antineoplásicos/farmacologia , Sistemas de Liberação de Medicamentos , Neoplasias Ovarianas/tratamento farmacológico , Animais , Antineoplásicos/efeitos adversos , Ensaios Clínicos como Assunto , Comportamento Cooperativo , Desenho de Fármacos , Feminino , Humanos , Neoplasias Ovarianas/patologia , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: Ovarian cancer is the fourth cause of death from gynaecological cancer and cervical cancer is the first in women <45 years old in developing countries. The aim of this article is to review the role of topotecan (Hycamtin), a semi-synthetic alkaloid derivative of camptothecin, in ovarian and cervical cancer in monotherapy and in combination. METHODS: This article reviews the mechanism of action, pharmacokinetics, toxicity and efficacy of topotecan. The paper also reports the principal phases II and III studies of topotecan in advanced or recurrent ovarian and cervical cancer. RESULTS: Topotecan (Hycamtin), currently indicated for the treatment of relapsed ovarian cancer, has demonstrated activity both in platinum-sensitive and in platinum-resistant disease. The combination cisplatin-topotecan for the treatment of advanced and recurrent cervical cancer has demonstrated a clinical benefit in terms of response rate, overall survival and progression free survival. Haematological toxicity of topotecan also is easy to manage and not cumulative, especially with the weekly scheduled recently introduced in clinical practice. CONCLUSION: Topotecan (Hycamtin) will continue to play a role in the treatment of advanced ovarian and cervical cancer, in monotherapy or in combination with other cytotoxic agents.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias dos Genitais Femininos/tratamento farmacológico , Topotecan/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Interações Medicamentosas , Feminino , Humanos , Topotecan/administração & dosagem , Topotecan/farmacocinéticaRESUMO
Brostallicin (PNU-166196), a-bromo-acrylamido tetra-pyrrole derivative, showed high cytotoxic potency and myelotoxicity dramatically reduced compared with other minor groove DNA-binding agents. In the presence of high intracellular glutathione concentrations, which are associated with resistance to chemotherapy, brostallicin performs a DNA minor groove attack leading to alkylation of DNA nucleophilic functions. In preclinical models, the antitumor activity of brostallicin has been tested in ovarian cancer xenografts, L1210 murine leukemia models, renal, colon and prostatic cancer cells and glutathione-S-transferase (GST) transfected human breast carcinoma cells. In clinical setting, the antitumor activity of brostallicin has been tested in ovarian cancer and in soft tissue sarcoma patients. A clear therapeutic advantage is also observed in preclinical models when brostallicin is combined with anticancer agents such as cisplatin (CDDP), doxorubicin, irinotecan and docetaxel. Brostallicin was also tested in combination with gefitinib, imatinib and bevacizumab in in vitro and in vivo studies, documenting a synergistic effect and with cetuximab showing an additive effect. Preliminary results of activity and toxicities of brostallicin in Phase I and II studies will be provided.