Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
1.
Int J Cancer ; 151(10): 1791-1803, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-35695283

RESUMO

Inhibitors of poly(ADP-ribose) polymerase (PARPi) are increasingly employed as salvage therapy in epithelial ovarian cancer (EOC), but cytotoxic drug exposure along with PARP inhibition may favor development of hematological disorders. In our study, of 182 women with EOC treated with PARPi, 16 (8.7%) developed therapy-related myeloid neoplasms (t-MNs), with 12 cases of myelodysplasia and 4 of acute myeloid leukemia. All experienced persistent cytopenia after PARPi discontinuation. Seven patients had del(5q)/-5 and/or del(7q)/-7, nine had a complex karyotype and TP53 mutations, recently reported as risk factor for t-MNs in EOC post-PARPi, were found in 12 out of 13 tested patients. Four patients had a rapid and fatal outcome, one had stable disease, eleven underwent induction therapy, followed by allogeneic hematopoietic cell transplantation in seven. Three of these 11 patients experienced refractory disease, and 8 had complete remission. During a 6.8 months (range 2.3-49) median observation time, 3 out of 16 patients were alive, with one surviving patient free of both solid and hematological tumors. Ten patients died because of leukemia, two because of transplant-related events, one from heart failure. Five more patients experienced persistent cell blood count abnormalities following PARPi discontinuation, without reaching MDS diagnostic criteria. A customized Myelo-panel showed clonal hematopoiesis in all five patients. These findings confirm the actual risk of t-MNs in EOC patients after chemotherapy and prolonged PARPi therapy. The management of these patients is complex and outcomes are extremely poor. Careful diagnostic procedures are strongly recommended whenever unusual cytopenias develop in patients receiving PARPi therapy.


Assuntos
Segunda Neoplasia Primária , Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/tratamento farmacológico , Análise Citogenética , Feminino , Humanos , Segunda Neoplasia Primária/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Poli(ADP-Ribose) Polimerases/uso terapêutico , Terapia de Salvação
2.
Int J Cancer ; 148(1): 170-177, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32856727

RESUMO

We investigated the occurrence and management of therapy-related hematological disorders (tr-HDs) in women with epithelial ovarian cancer (EOC) exposed to poly-ADP-ribose polymerase inhibitors (PARPi), after previous chemotherapy. We analyzed 130 consecutive EOC patients treated with PARPi at the European Institute of Oncology, Milan. In line with the literature, overall survival of the entire population was 37% at 5.5 years (89% were advanced stages). Cell blood counts were collected prior to start PARPi, at each new cycle and at monthly intervals. Patients displaying persistent and/or marked hematological abnormalities underwent bone marrow evaluation, with cytogenetic and molecular analysis. Nine patients (6,9%) developed tr-HDs, after a median 22.8 months of PARPi exposure. Two patients died early and could not be treated. Two patients have no indication for active treatment and are presently under close hematological monitoring. Five patients underwent chemotherapy followed, in three cases, by allogeneic hematopoietic transplantation: three patients are in complete remission of their hematological and gynecological malignancies at 13, 19, and 25 months; the remaining two patients died due to progression of their hematological disease. We show the potential risk of hematological disorders in EOC patients treated with chemotherapy and prolonged PARPi therapy. In our series, tr-HDs incidence was higher compared to recent reports in large series. Our observations suggest careful monitoring in order to conclusively define, on large series and prolonged follow-up, the actual risk of tr-HDs in patients under PARPi. Notably, prompt diagnosis of hematological abnormalities and appropriate management allow achievement of remission from severe hematological complications, at least in most patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Epitelial do Ovário/tratamento farmacológico , Doenças Hematológicas/diagnóstico , Neoplasias Ovarianas/tratamento farmacológico , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Adulto , Idoso , Contagem de Células Sanguíneas , Medula Óssea/patologia , Carcinoma Epitelial do Ovário/mortalidade , Feminino , Doenças Hematológicas/induzido quimicamente , Doenças Hematológicas/epidemiologia , Doenças Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Humanos , Incidência , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Estudos Retrospectivos , Transplante Homólogo
3.
Anticancer Res ; 38(6): 3627-3634, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29848719

RESUMO

AIM: To assess the patterns of recurrence and clinical outcomes of patients with cervical adenocarcinoma who underwent neoadjuvant platinum-based chemotherapy (NACT) followed by radical hysterectomy. PATIENTS AND METHODS: Data were retrospectively analyzed for 82 patients with International Federation of Gynecology and Obstetrics stage Ib2-IIb cervical adenocarcinoma who underwent this chemo-surgical treatment. The median follow-up of survivors was 89 months (range=5-208 months). RESULTS: Pathological complete response, optimal response and suboptimal response with intra-cervical residual disease were obtained in five (6%), 10 (12%) and 36 (44%) patients, respectively. Adjuvant external-beam radiotherapy with or without concurrent chemotherapy was administered to 47 patients. Nineteen (23%) out of the 82 patients experienced recurrence after a median of 12 months (range=5.3-86.8 months). Recurrent disease was pelvic in 12 (63%) patients, extra-pelvic in five (26%), and both pelvic and extra-pelvic in two (10%). According to pathological response, tumor relapsed in 10% of optimal responders, 14% of sub-optimal responders with intra-cervical residual disease, and 36% of sub-optimal responders with extra-cervical residual disease or non-responders. Five-year recurrence-free and overall survival were 77% and 84%, respectively. Patients who achieved an optimal response or sub-optimal response with intra-cervical residual disease had better 5-year recurrence-free (87% vs. 64%, p=0.017) and overall (92% vs. 74%, p=0.012) survival than those who had sub-optimal response with extra-cervical residual disease or no response. The latter had a 1.441-fold higher risk of recurrence and a 1.652-fold higher risk of death than those who obtained an optimal response or a sub-optimal response with intra-cervical residual disease. CONCLUSION: NACT followed by radical hysterectomy may be an option for patients with stage Ib2-IIb adenocarcinoma of the uterine cervix.


Assuntos
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Histerectomia/métodos , Neoplasias do Colo do Útero/terapia , Adenocarcinoma/patologia , Adulto , Idoso , Quimiorradioterapia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia , Adulto Jovem
4.
Anticancer Res ; 37(9): 5241-5248, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28870960

RESUMO

BACKGROUND/AIM: Occult cancers' reported rates vary from 2-12% and serous tubal intraepithelial carcinomas (STICs) have been identified in 3-12% of the prophylactically removed tubes of women carrying a BRCA mutation. The aim of this study was to evaluate the incidence of tubal minor epithelial atypia (STIL), STIC, and occult invasive cancer and to evaluate the cancer-specific mortality in a prospective series of women at higher risk of ovarian and breast cancer undergoing risk-reducing salpingo-oophorectomy (RRSO) n a tertiary cancer center. PATIENTS AND METHODS: A series of RRSO specimens (including endometrial biopsy) from women carrying a BRCA mutation, BRCA-unknown and BRCA-negative were collected between January 1998 and April 2016 at the Division of Gynecology at the European Institute of Oncology. Inclusion criteria were: asymptomatic women who had a negative gynecologic screening within 3 months prior to RRSO. Exclusion criteria were: women with ovarian/tubal cancer prior to RRSO. RESULTS: A total of 411 women underwent RRSO. Median age at RRSO was 47.0 years (range=32-70 years); 75.2% had a history of breast cancer. Fifteen women were diagnosed with an occult cancer (7 STIC, 4 invasive cancers, 2 breast cancers metastatic to the adnexa, 2 endometrial cancer) (3.6%). Sixteen showed a STIL (3.9%). When excluding cases with preoperative positive markers, the occult invasive cancer rate drops to 1.5%. CONCLUSION: Our study, covering an 18-year period, shows a substantial low risk of occult cancer among a high-risk population of women undergoing RRSO. Our data still support the indication for RRSO in higher-risk patients. An endometrial biopsy should also be routinely obtained as it raises the chances of detecting occult endometrial cancers that may be otherwise missed.


Assuntos
Neoplasias da Mama/cirurgia , Neoplasias Ovarianas/cirurgia , Ovariectomia , Salpingectomia , Adulto , Idoso , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Demografia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Mutação/genética , Invasividade Neoplásica , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Estudos Prospectivos , Fatores de Risco , Proteína Supressora de Tumor p53/metabolismo
5.
J Clin Oncol ; 23(4): 751-8, 2005 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-15613698

RESUMO

PURPOSE: To assess whether the interval from primary surgery to the start of taxane- plus platinum-based chemotherapy has any impact on the clinical outcome of advanced ovarian cancer patients. PATIENTS AND METHODS: The study was conducted on 313 patients who underwent surgery followed by taxane- plus platinum-based chemotherapy. The median follow-up of survivors was 30.7 months (range, 6 to 109 months). RESULTS: The 25%, 50%, and 75% quantiles of intervals from surgery to the start of chemotherapy were 11, 21, and 31 days, respectively. After the sixth cycle, 102 patients achieved a pathologic complete response at second-look surgery and 98 obtained a clinical complete response but were not submitted to second-look surgery. Taking into consideration the best assessed response, a complete (either clinical or pathologic) response was found in 200 patients. Residual disease (< or = 1 v > 1 cm; P < .0001) and ascites (absent v present; P = .003) were independent predictive factors for achieving a complete response, whereas residual disease (P = .001) and stage (IIc to III v IV; P = .04) were independent prognostic variables for survival. Conversely, statistical analyses failed to detect significant differences in complete response rates and survival among patients with an interval from surgery to chemotherapy shorter than 11 days, 12 to 21 days, 22 to 31 days, and longer than 31 days. CONCLUSION: The interval from surgery to the start of taxane- plus platinum-based chemotherapy seems to have neither a predictive value for response to treatment nor a prognostic relevance for survival of advanced ovarian cancer patients.


Assuntos
Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Carboplatina/administração & dosagem , Cisplatino/administração & dosagem , Terapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/cirurgia , Paclitaxel/administração & dosagem , Estudos Retrospectivos , Fatores de Tempo
6.
Gynecol Oncol ; 85(3): 445-50, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12051872

RESUMO

OBJECTIVE: One hundred and forty-eight consecutive gynecological oncological patients aged >or=70 were administered chemotherapy during the years 1990-2000. METHODS: Median age was 73 years (range 70-84). Fifty-five (37.2%) women were over 75 years old. One or more comorbid conditions were present in 118 (79.7%) patients. Standard schedules were administered to 97.3% of cases, with a total number of 1046 cycles of therapy administered (median, 6; range, 1-35, per patient). RESULTS: Of a total of 233 chemotherapy regimens globally administered, G3-G4 hematological toxicity was documented in 38.2% of cases. Only 10 (6.8%) of the 148 patients discontinued treatment because of G3-G4 hematological toxicity. No severe nonhematological toxicity was observed. Two dose reductions and three treatment delays, but no discontinuation of treatment, were required during second-line regimens. Treatment delay >7 days was required in 16.9% of cases. CONCLUSIONS: Chronological age did not adversely influence the ability to receive aggressive treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias dos Genitais Femininos/tratamento farmacológico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Contraindicações , Relação Dose-Resposta a Droga , Feminino , Neoplasias dos Genitais Femininos/complicações , Humanos , Estudos Retrospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA