RESUMO
IMPORTANCE: The efficacy of taxane plus platinum regimens has been demonstrated for advanced or recurrent endometrial cancer; however, it has not been assessed in postoperative adjuvant chemotherapy for endometrial cancer. OBJECTIVE: To evaluate the clinical benefit of taxane plus platinum compared with standard doxorubicin plus cisplatin as postoperative adjuvant chemotherapy in endometrial cancer. DESIGN, SETTING, AND PARTICIPANTS: In this multicenter, open-label, phase 3 randomized clinical trial, patients with endometrial cancer at high-risk stage I or II or stage III or IV that did not extend beyond the abdominal cavity and had 2 cm or greater residual tumor were included from 118 institutions in Japan from November 24, 2006, to January 7, 2011. Data was analyzed from March 15, 2017, to June 30, 2017. INTERVENTIONS: Eligible patients were randomly assigned (1:1:1) to receive 6 cycles of doxorubicin, 60 mg/m2, plus cisplatin, 50 mg/m2, on day 1; docetaxel, 70 mg/m2, plus cisplatin, 60 mg/m2, on day 1; or paclitaxel, 180 mg/m2, plus carboplatin (area under the curve, 6.0 mg/mL × min) on day 1 every 3 weeks. MAIN OUTCOMES AND MEASURES: The primary end point was progression-free survival. Secondary end points were overall survival, occurrence of adverse events, tolerability, and status of lymph node dissection. RESULTS: Among 788 eligible patients, the median (SD) age was 59 (22-74) years; 263 patients were assigned to doxorubicin plus cisplatin treatment, 263 patients to docetaxel plus cisplatin treatment, and 262 patients to paclitaxel plus carboplatin treatment. The number of patients who did not complete 6 cycles was 53 (20.1%) for the doxorubicin plus cisplatin group, 45 (17.1%) for the docetaxel plus cisplatin group, and 63 (24.0%) for the paclitaxel plus carboplatin group. Tolerability of these regimens were not statistically different. After a median follow-up period of 7 years, there was no statistical difference of progression-free survival (doxorubicin plus cisplatin, 191; docetaxel plus cisplatin, 208; paclitaxel plus carboplatin, 187; P = .12) or overall survival (doxorubicin plus cisplatin, 217; docetaxel plus cisplatin, 223; paclitaxel plus carboplatin, 215; P = .67) among the 3 groups. The 5-year progression-free survival rate was 73.3% for the doxorubicin plus cisplatin group, 79.0% for the docetaxel plus cisplatin group, and 73.9% for the paclitaxel plus carboplatin group, while the 5-year overall survival rates were 82.7%, 88.1%, and 86.1%, respectively. CONCLUSIONS AND RELEVANCE: There was no significant difference of survival among patients receiving doxorubicin plus cisplatin, docetaxel plus cisplatin, or paclitaxel plus carboplatin as postoperative adjuvant chemotherapy for endometrial cancer. Because each regimen showed adequate tolerability but different toxic effects, taxane plus platinum regimens may be a reasonable alternative to treatment with doxorubicin plus cisplatin. TRIAL REGISTRATION: UMIN-CTR identifier: UMIN000000522.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Carboplatina/administração & dosagem , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Neoplasias do Endométrio/tratamento farmacológico , Paclitaxel/administração & dosagem , Taxoides/administração & dosagem , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Carboplatina/efeitos adversos , Quimioterapia Adjuvante , Cisplatino/efeitos adversos , Progressão da Doença , Doxorrubicina/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Risco , Taxoides/efeitos adversos , Resultado do TratamentoRESUMO
OBJECTIVE: Recently, we established new histopathological subtypes of high-grade serous ovarian cancer (HGSOC) that include the mesenchymal transition (MT) type, the immune reactive (IR) type, the solid and proliferative (SP) type and the papillo-glandular (PG) type. Furthermore, we identified that the mesenchymal transcriptome subtype might be sensitive to taxane. We investigated whether these different histopathological subtypes of HGSOC require individualized chemotherapy for optimal treatment. METHODS: We conducted the Japanese Gynecologic Oncology Group (JGOG) 3016A1 study, wherein we collected hematoxylin and eosin slides (total nâ¯=â¯201) and performed a histopathological analysis of patients with HGSOC registered in the JGOG3016 study, which compared the efficacy of conventional paclitaxel and carboplatin (TC) and dose-dense TC (ddTC). We analyzed the differences in progression-free survival (PFS) and overall survival (OS) among the four histopathological subtypes. We then compared the PFS between the TC group and the ddTC group for each histopathological subtype. RESULTS: There were significant differences in both PFS and OS among the four histopathological subtypes (pâ¯=â¯0.001 and pâ¯<â¯0.001, respectively). Overall, the MT subtype had the shortest PFS (median 1.4â¯y) and OS (median 3.6â¯y). In addition, the MT subtype had a longer PFS in the ddTC group (median 1.8â¯y) than in the TC group (median 1.2â¯y) (pâ¯=â¯0.01). Conversely, the other types had no significant difference in PFS when the two regimens were compared. CONCLUSIONS: The MT type of HGSOC is sensitive to taxane; therefore, the ddTC regimen is recommended for this histopathological subtype.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cistadenocarcinoma Seroso/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/patologia , Feminino , Perfilação da Expressão Gênica , Humanos , Japão , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Ovário/patologia , Intervalo Livre de Progressão , Análise de SobrevidaAssuntos
Adenocarcinoma/etiologia , Adenocarcinoma/patologia , Adenomiose/complicações , Neoplasias da Mama/cirurgia , Neoplasias do Endométrio/etiologia , Neoplasias do Endométrio/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/terapia , Adenomiose/diagnóstico por imagem , Adenomiose/terapia , Anastrozol/administração & dosagem , Inibidores da Aromatase/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/terapia , Feminino , Humanos , Imageamento por Ressonância Magnética , Mastectomia , Pessoa de Meia-IdadeRESUMO
The therapeutic value of para-aortic lymphadenectomy (PAL) in women with endometrial cancer (EC) remains uncertain. We retrospectively analysed 25 patients with stage IIIc EC (17 stage IIIC1; 8 IIIC2) who were treated in our institution. All subjects had undergone pelvic lymphadenectomies in which para-aortic nodes were sampled, or removed only when these nodes were enlarged. Sampling of para-aortic nodes or PAL was performed in all patients with stage IIIC2 disease and one of 17 with stage IIIC1 disease. Para-aortic lymph nodes were the most frequent site of recurrence in stage IIIC1 patients, but no such recurrences occurred in stage IIIC2 patients. Overall survival tended to be shorter in stage IIIC1 patients than stage IIIC2 patients. Our findings indicate that PAL improves the outcomes of patients with EC and high risk of para-aortic lymph node metastasis, such as those with positive pelvic lymph nodes or enlargement of para-aortic lymph nodes. Impact statement Para-aortic lymph node (PALN) metastases are important prognostic factors in endometrial cancer. Overall survival of patients with stage IIIC1 disease is generally longer than for those with stage IIIC2 disease. Retrospective studies - but no prospective studies - have suggested that para-aortic lymphadenectomy (PAL) provides a survival benefit. In our institution, we had performed PAL or para-aortic sampling for patients with enlarged PALNs; therefore, as most IIIC1 patients had no enlarged PALNs, they underwent pelvic lymphadenectomy only, whereas all IIIC2 patients had enlarged PALNs and underwent pelvic lymphadenectomy and PAL or PALN sampling in addition to pelvic lymphadenectomy. However, under this policy, survival of stage IIIC1 patients was not better than for stage IIIC2 patients. Our retrospective study indicates a survival benefit for PAL in patients with pelvic node-positive or enlarged PALN. PAL warrants a prospective randomised trial to see whether it should be a standard treatment in these patients.
Assuntos
Adenocarcinoma/cirurgia , Neoplasias do Endométrio/cirurgia , Excisão de Linfonodo , Recidiva Local de Neoplasia/patologia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Aorta , Intervalo Livre de Doença , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Humanos , Metástase Linfática/patologia , Recidiva Local de Neoplasia/mortalidade , Estadiamento de Neoplasias , Estudos RetrospectivosRESUMO
OBJECTIVES: The adenocarcinoma of the uterine cervix tends to arise in women of childbearing age. Conservative treatment by conization is an alternative to a hysterectomy that allows future pregnancy; however, much less is known about the management of adenocarcinoma because of its rarity and relatively short time frame of follow-up. The purpose of this study was to determine the long-term outcome of patients treated by conization alone. METHODS: All patients diagnosed to have FIGO (International Federation of Gynecology and Obstetrics) stage IA1 cervical adenocarcinoma between 1990 and 2004 with more than 5 years' follow-up at 2 institutions were reviewed. Information was abstracted on clinical data including margin status of conization and recurrence. RESULTS: Twenty-seven patients were identified, and 10 patients who expressed a strong desire to preserve fertility were offered a conization and careful surveillance without hysterectomy. The median age was 35 years, and 40% were nulliparous. All tumors were endocervical-type adenocarcinoma, and all tumors were grade 1. None had lymphovascular space invasion. Two patients had a repeated conization because of a positive margin. No recurrence was observed during an average follow-up of 75 months. CONCLUSIONS: Although further studies on the management of microinvasive cervical adenocarcinoma are desirable, conization seems to be acceptable treatment modality for patients with stage IA1 cervical adenocarcinoma who desire to preserve their fertility. A careful and long-term follow-up is needed because of lack of sufficient evidence for the safety of this treatment.
Assuntos
Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Conização/métodos , Recidiva Local de Neoplasia/patologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Adulto , Biópsia por Agulha , Estudos de Coortes , Conização/efeitos adversos , Feminino , Seguimentos , Humanos , Histerectomia/métodos , Imuno-Histoquímica , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Gravidez , Taxa de Gravidez , Reoperação , Estudos Retrospectivos , Medição de Risco , Fatores de Tempo , Resultado do TratamentoAssuntos
Neoplasias dos Genitais Femininos/cirurgia , Perna (Membro) , Linfedema , Complicações Pós-Operatórias , Terapia Combinada , Diagnóstico Diferencial , Diagnóstico por Imagem , Feminino , Procedimentos Cirúrgicos em Ginecologia , Humanos , Perna (Membro)/patologia , Linfedema/diagnóstico , Linfedema/epidemiologia , Linfedema/etiologia , Linfedema/terapia , Modalidades de Fisioterapia , Prognóstico , Fatores de TempoRESUMO
OBJECTIVE: To clarify the ratio of diseases suspected when malignant glandular cells are observed on cervical cytology. STUDY DESIGN: Seventy cases of cervical adenocarcinoma/adenosquamous carcinoma, 207 cases of endometrial adenocarcinoma, 7 cases of tubal adenocarcinoma and 83 cases of ovarian adenocarcinoma were reviewed. The positive rate in cervical cytology performed 3 months before surgery was calculated. Based on the positive rate for each entity and the number of cases treated in the previous 10 years, we estimated the incidence of disease responsible for malignant glandular cells on cytology. RESULTS: The positive rate was 93% in cervical adenocarcinoma/adenosquamous carcinoma, 45% in endometrial adenocarcinoma, 14% in tubal adenocarcinoma and 6% in ovarian adenocarcinoma. These positive rates and case numbers at our institute indicated the percentage of suspicious diseases to be 38% for cervical aaenocarcinoma/adenosquamous carcinoma, 53% for endometrial adenocarcinoma, 1% for tubal adenocarcinoma and 8% for ovarian adenocarcinoma. CONCLUSION: When a cytologic specimen suggested the existence of adenocarcinoma, the most probable disease was endometrial adenocarcinoma, and the second was cervical adenocarcinoma/adenosquamous carcinoma. Adnexal malignancies were responsible in 9% of cases. In the case of positive cervical cytology suggesting adenocarcinoma, the ratio of suspicious diseases is as valuable as the cytologic findings for the differential diagnosis.