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1.
Medicine (Baltimore) ; 98(39): e17234, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574835

RESUMO

Locally advanced cervical carcinoma has a poor prognosis. Neoadjuvant chemotherapy (NACT) can reduce tumor size and improve tumor resection rate, but its use in large locally advanced cervical carcinoma is controversial. This study aimed to evaluate the treatment and prognosis of NACT in patients with cervical carcinoma stage IB2 or IIA2.This was a retrospective cohort study of patients who underwent type-C radical surgery and pelvic lymphadenectomy due to cervical carcinoma stage IB2/IIA2 between 2/2014 and 12/2016 at the Second Hospital of Jilin University. The patients were grouped according to whether they received NACT (paclitaxel and a platinum salt) or not. Overall survival (OS) and progression-free survival (PFS) were compared between the 2 groups.Of the 144 patients, 60 (41.7%) received NACT. A total of 119 patients underwent postoperative radiation therapy, of which 97 received radiation therapy alone and 22 received concurrent chemoradiotherapy. The adverse reactions in the NACT group were mainly hematologic toxic reactions, but were tolerated. No grade ≥III adverse reactions were observed. NACT did not significantly affect the PFS (P = .453) and OS (P = .933) between the 2 groups. No factor was found to be independently associated with OS or PFS (all P > .05).Compared with patients who underwent surgery with/without radiotherapy and/or chemotherapy, NACT using paclitaxel and a platinum salt does not improve the prognosis and lymph node metastasis rate of locally advanced cervical carcinoma in Chinese patients.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/mortalidade , Histerectomia/mortalidade , Terapia Neoadjuvante/mortalidade , Neoplasias do Colo do Útero/mortalidade , Adulto , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/mortalidade , China , Feminino , Seguimentos , Humanos , Histerectomia/métodos , Excisão de Linfonodo/mortalidade , Metástase Linfática , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Paclitaxel/administração & dosagem , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia
2.
Zhonghua Fu Chan Ke Za Zhi ; 54(9): 588-594, 2019 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-31550774

RESUMO

Objective: To investigate the efficacy and side effect of paclitaxel liposome for neoadjuvant chemotherapy (NACT) in locally advanced cervical cancer. Methods: This study were included 265 cervical cancer patients staging Ⅰb2 and Ⅱa2 who underwent paclitaxel-platinum NACT followed by radical surgery from June 2008 to December 2016 in the Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences. All patients were classified into two groups with 106 patients in paclitaxel liposome group and 159 patients in traditional paclitaxel group. The difference in clinicopathologic characteristics, efficacy and side effect were analyzed retrospectively between the two groups. Results: (1) Clinicopathologic characteristics: there were no significant difference in clinicopathologic characteristics between the two groups, including age, body mass index, clinical stage, pathological histology, cycles of NACT, combined platinum regimen, lymph-vascular space invasion, lymph node metastasis, deep stromal invasion, and postoperative adjuvant therapy (all P>0.05). (2) Efficacy: after NACT, the overall response occurred in 90 (15 complete response plus 75 partial response) of 106 cases in the paclitaxel liposome group versus 131 (21 complete response plus 110 partial response) of 159 cases in the traditional paclitaxel group without statistical significance (84.9% vs 82.4%; χ(2)=0.291, P=0.590). A total of 248 patients received surgery after NACT and were evaluable in survival. The 5-year recurrence-free survival (RFS) rate and 5-year overall survival (OS) rate of these patients was 85.1% and 88.2%. The 5-year RFS rate in the paclitaxel liposome group was 85.9% compared with 85.2% in the traditional paclitaxel group, while the corresponding 5-year OS rate was 88.5% and 88.7%, respectively. There was no statistically significant difference in efficacy between the two groups (P=0.968, P=0.797). (3) Side effect: the incidence of allergic reaction between the paclitaxel liposome group and the traditional paclitaxel group was 0 versus 1.9% (3/159) without statistical significance (P=0.277). But the incidence of neurotoxicity in the paclitaxel liposome group significantly decreased compared with the traditional paclitaxel group (6.6% vs 15.7%, P<0.05), as well as the incidence of alopecia (67.9% vs 79.2%, P<0.05) and myalgia (17.9% vs 28.9%, P<0.05). However, significant differences were not found in terms of hematological toxicity, gastrointestinal reaction, and hepatic function damage (P>0.05). Conclusion: In paclitaxel-platinum NACT of local advanced cervical cancer, paclitaxel liposome can achieve similar efficacy compared with traditional paclitaxel, but paclitaxel liposome is helpful in decreasing the toxicity of neurotoxicity, alopecia and myalgia.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Quimioterapia Adjuvante/efeitos adversos , Terapia Neoadjuvante/efeitos adversos , Paclitaxel/administração & dosagem , Neoplasias do Colo do Útero/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Feminino , Humanos , Lipossomos , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
3.
Zhonghua Wei Chang Wai Ke Za Zhi ; 22(8): 774-780, 2019 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-31422617

RESUMO

Objective: To investigate the clinical value of laparoscopic peritoneal dialysis catheter implantation in peritoneal chemotherapy for gastric cancer with peritoneal metastasis. Methods: From January 2019 to June 2019, the clinical data of 6 patients diagnosed as gastric cancer with peritoneal metastasis were retrospectively analyzed in the Gastrointestinal Surgery Department of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine. Five were male and 1 was female. The median age was 69.5 (28-77) years. The median body mass index (BMI) was 22.8 (19.6-23.5). All procedures were performed under general anesthesia with endotracheal intubation. The patient's body position and facility layout in the operating room were consistent with those of laparoscopic gastrectomy. The operator's position: the main surgeon was located on the right side of the patient, the first assistant stood on the left side of the patient, and the scopist stood between the patient's legs. Surgical procedure: (1) trocar location: three abdominal trocars was adopted, with one 12 mm umbilical port for the 30° laparoscope (point A). Location of the other two trocars was dependent on the procedure of exploration or biopsy as well as the two polyester cuff position of the peritoneal dialysis catheter: Usually one 5 mm port in the anterior midline 5 cm inferior to the umbilicus point was selected as point B to ensure that the distal end of the catheter could reach the Douglas pouch. The other 5 mm port was located in the right lower quadrant lateral to the umbilicus to establish the subcutaneous tunnel tract, and the proximal cuff was situated 2 cm away from the desired exit site (point C).(2) exploration of the abdominal cavity: a 30° laparoscope was inserted from 12 mm trocar below the umbilicus to explore the entire peritoneal cavity. The uterus and adnexa should be explored additionally for women. Once peritoneal metastasis was investigated and identified, primary laparoscopic peritoneal dialysis catheter implantation was performed so as to facilitate subsequent peritoneal chemotherapy. Ascites were collected for cytology in patients with ascites. (3) peritoneal dialysis catheter placement: the peritoneal dialysis catheter was introduced into the abdominal cavity from point A. Under the direct vision of laparoscopy, 2-0 absorbable ligature was reserved at the expected fixation point of the proximal cuff (point B) for the final knot closure. Non-traumatic graspers were used to pull the distal cuff of peritoneal dialysis catheter out of the abdominal cavity through point B. The 5-mm trocar was removed simultaneously, and the distal cuff was fixed between bilateral rectus sheaths at the anterior midline port site preperitoneally. To prevent subsequent ascites and chemotherapy fluid extravasation, the reserved crocheted wire was knotted. From point C the subcutaneous tunnel tract was created before the peritoneal steath towards the port site lateral to the umbilicus. Satisfactory catheter irrigation and outflow were then confirmed. Chemotherapy regimen after peritoneal dialysis catheterization: all patients began intraperitoneal chemotherapy on the second day after surgery. On the 1st and 8th day of each 3-weeks cycle, paclitaxel (20 mg/m(2)) was administered through peritoneal dialysis catheter, and paclitaxel (50 mg/m(2)) was injected intravenously. Meanwhile, S-1 was orally administered twice daily at a dose of 80 mg·m(-2)·d(-1) for 14 consecutive days followed by 7-days rest. To observe the patients' intraoperative and postoperative conditions. Results: All the procedures were performed successfully without intraoperative complications or conversion to laparotomy. No 30 day postoperative complications were observed. The median operative time was 33.5 (23-38) min. The median time to first flatus was 1(1-2) days, and the median postoperative hospital stay was 3 (3-4) days, without short-term complications within 30 days postoperatively. The last follow-up was up to July 10, 2019, and the patients were followed for 4(1-6) months. No ascites extravasation was observed and no death occurred in the 6 patients. There was no catheter obstruction or peritoneal fluid extravasation during and after chemotherapy. Conclusion: Laparoscopic peritoneal dialysis catheter implantation was safe and feasible for patients with peritoneal metastasis of gastric cancer. The abdominal exploration, tumor staging and the abdominal chemotherapy device implantation can be completed simultaneously, which could simplify the surgical approach, improve the quality of life for patients and further propose a new direction for the development of abdominal chemotherapy.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Paclitaxel/administração & dosagem , Diálise Peritoneal/instrumentação , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Cateterismo/métodos , Cateteres de Demora , China , Feminino , Humanos , Infusões Intravenosas , Infusões Parenterais , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal/métodos , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Adulto Jovem
4.
Anticancer Res ; 39(8): 4379-4383, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366533

RESUMO

BACKGROUND/AIM: Dose-dense doxorubicin and cyclophosphamide (ddAC) followed by dose-dense paclitaxel (ddP) (ddAC-P) has improved disease-free survival of patients with breast cancer. The aim of this study was to evaluate the safety and relative dose intensity (RDI) of ddAC-P administered together with pegfilgrastim. PATIENTS AND METHODS: Between May 2015 and Aug 2017, 44 patients were retrospectively reviewed; they were administered 4 cycles of ddAC, followed by 4 cycles of ddP. Pegfilgrastim (3.6 mg) was administered in every cycle. RESULTS: The mean RDIs for ddAC-P, ddAC, and ddP were 95.0%, 94.5%, and 93.3%, respectively. The prevalence of high RDIs (≥85%) for ddAC-P, ddAC, and ddP was 90.9%, 84.1%, and 88.6%, respectively. Seven of the 10 patients with low RDIs experienced grade 1 or 2 fever. CONCLUSION: DdAC-P administered together with pegfilgrastim (3.6 mg) appears to be feasible and maintains RDI in most of Japanese patients with breast cancer. Rapid evaluation and proper management of fever may prevent low RDI.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Paclitaxel/administração & dosagem , Adulto , Idoso , Neoplasias da Mama/patologia , Ciclofosfamida/efeitos adversos , Relação Dose-Resposta a Droga , Doxorrubicina/efeitos adversos , Feminino , Filgrastim/administração & dosagem , Humanos , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Polietilenoglicóis/administração & dosagem
6.
J Surg Oncol ; 120(3): 550-557, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31267569

RESUMO

BACKGROUND AND OBJECTIVES: Hypertherm intraperitoneal chemotherapy (HIPEC) is increasingly used in the treatment of ovarian, tubal, and primary peritoneal cancer (OC). The aim was to evaluate short-term morbidity of cytoreductive surgery (CRS) and carboplatin HIPEC. METHODS: Prospective feasibility study performed from January 2016 to December 2017. Twenty-five patients with primary OC (FIGO III-IV) received upfront or interval CRS combined with carboplatin HIPEC at dose 800 mg/m 2 . Primary outcome measurements: grade 3 to 5 adverse events within 30 days according to Common Terminology Criteria for Adverse Events. Secondary outcome measurements: reoperation rate, length of hospital stay, readmission rate, and time from surgery to systemic chemotherapy administration. RESULTS: No deaths (grade 5) or grade 4 adverse events were observed. Eleven patients (44.0%) experienced at least one grade 3 adverse event, the most common being an infection (28.0%) and neutropenia (12.0%). The reoperation rate was 8.0%. The median hospital stay was 14 days (range 9-25 days), and five patients (25.0%) were readmitted within 30 days after surgery. Median time from surgery to the administration of the first dose of systemic chemotherapy was 41 days (range 24-81 days). CONCLUSION: Our small-scale prospective study supports that CRS and carboplatin HIPEC used for primary advanced-stage OC is feasible with acceptable morbidity.


Assuntos
Carboplatina/administração & dosagem , Carcinoma Epitelial do Ovário/terapia , Neoplasias das Tubas Uterinas/terapia , Hipertermia Induzida/métodos , Neoplasias Ovarianas/terapia , Neoplasias Peritoneais/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/cirurgia , Quimioterapia Adjuvante , Procedimentos Cirúrgicos de Citorredução/métodos , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias das Tubas Uterinas/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Paclitaxel/administração & dosagem , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Estudos Prospectivos
7.
Oncology ; 97(4): 202-205, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31288226

RESUMO

Based on the results of several phase 3 randomized trials, "maintenance therapy" (prolonged treatment after an initial response to cytotoxic chemotherapy) has assumed a critical role in the routine care of advanced epithelial ovarian cancer. While earlier data had provided support for this therapeutic concept in disease management (e.g., multiple cycles of single-agent paclitaxel following a clinical complete response to a platinum/paclitaxel regimen), more recent data has revealed both the efficacy and safety of the anti-angiogenesis agent, bevacizumab, and several PARP inhibitors when employed in this clinical setting.


Assuntos
Tratamento Farmacológico/métodos , Oncologia/tendências , Neoplasias Ovarianas/tratamento farmacológico , Bevacizumab/administração & dosagem , Feminino , Humanos , Neoplasias Ovarianas/imunologia , Paclitaxel/administração & dosagem , Platina/administração & dosagem , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
8.
Gynecol Oncol ; 154(3): 554-557, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31285082

RESUMO

OBJECTIVE: We evaluated the efficacy and safety of the combination of paclitaxel, carboplatin, and bevacizumab in patients with advanced or recurrent cervical cancer. METHODS: Subjects included patients with advanced or recurrent cervical cancer not amenable to curative treatment with surgery or radiation therapy. Treatment consisted of paclitaxel 175 mg/m2, carboplatin area under the curve 6 mg/mL/min, and bevacizumab 15 mg/kg every 21 days until disease progression, complete remission, or limiting toxicity. The primary endpoint was the objective response. RESULTS: In total, 34 patients received a median of 6 treatment cycles (range 2-25). The median follow-up period was 18.5 months (range 2-29). The objective response was 88% (95% confidence interval: 72.5%-96.7%). Seventeen patients (50%) experienced complete response, whereas 13 patients experienced (38%) partial response with a median duration of 6 months. Grades 3 and 4 hematologic toxicities manifested as neutropenia in 14 (41.2%), leukopenia in 14 (41.2%), anemia in 11 (32.4%), and thrombocytopenia in 9 (26.5%) patients. One patient who underwent prior pelvic irradiation developed grade 2 rectovaginal fistula. CONCLUSION: The combination of paclitaxel, carboplatin, and bevacizumab is effective and safe in patients with advanced or recurrent cervical cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos
9.
Gynecol Oncol ; 154(3): 524-530, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31353053

RESUMO

OBJECTIVE: To determine the feasibility of pharmacologic beta-adrenergic blockade in women with newly diagnosed stage II-IV epithelial ovarian cancer (EOC) throughout primary treatment. METHODS: Patients initiated propranolol prior to beginning chemotherapy or surgery. Feasibility was assessed as proportion able to complete 6 chemotherapy cycles while on adrenergic suppression. Descriptive statistics summarized surveys, and paired changes were analyzed using signed rank tests. Random-intercept Tobit models examined immune response. RESULTS: Median age was 59.9; 88.5% were stage IIIC/IV; and 38.5% underwent primary debulking. Thirty-two patients were enrolled; 3 excluded because they never took propranolol; an additional 3 didn't meet inclusion criteria, leaving 26 evaluable. Eighteen of 26 (69%), 90% credible interval (CI) of 53-81%, completed 6 chemotherapy cycles plus propranolol (an 82% posterior probability that the true proportion of success is ≥60%). Among the 23 patients with baseline and six month follow up data, overall QOL, anxiety, and depression improved (P < 0.05) and leukocyte expression of pro-inflammatory genes declined (P = 0.03) after completion of therapy. Decrease from baseline of serum IL-6 and IL-8 preceded response to chemotherapy (P < 0.0014). Change from baseline IL-10 preceded complete response. CONCLUSION: Use of propranolol during primary treatment of EOC is feasible and treatment resulted in decrease in markers of adrenergic stress response. In combination with chemotherapy, propranolol potentially results in improved QOL over baseline.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Propranolol/administração & dosagem , Antagonistas Adrenérgicos beta/administração & dosagem , Idoso , Carboplatina/administração & dosagem , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/imunologia , Carcinoma Epitelial do Ovário/cirurgia , Quimioterapia Adjuvante , Citocinas/sangue , Citocinas/genética , Citocinas/imunologia , Estudos de Viabilidade , Feminino , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/imunologia , Humanos , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Estudos Longitudinais , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/cirurgia , Paclitaxel/administração & dosagem , Projetos Piloto , Estudos Prospectivos , Qualidade de Vida
10.
AAPS PharmSciTech ; 20(5): 212, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31165303

RESUMO

Psoriasis is an autoimmune disorder disease with pink-colored plaques and excessive proliferation which is hard to be cured completely. The study focuses on the anti-psoriatic efficacy of O/O paclitaxel ointment which can promote the assembly of microtubules and lead to death of overproliferation cells of the psoriasis epidermal. A high-speed shearing method was adopted in preparing the ointment, in which propylene carbonate was used as the internal oil phase to solve paclitaxel completely. It was characterized by the appearance, particle size, rheological behavior, and in vitro release. The amount of paclitaxel retained in normal skin and psoriatic skin was 1.00 ± 0.50 versus 1.53 ± 0.48 µg/g for 0.03% PTX ointment, 1.30 ± 0.39 versus 2.77 ± 0.49 µg/g for 0.1% PTX ointment, and 2.22 ± 0.92 versus 6.65 ± 0.87 µg/g for 0.3% PTX ointment, respectively, which implied that paclitaxel could better retain in inflamed skin than in normal skin; also the amount of drug retained in the skin was proportional to drug content. Paclitaxel ointment displayed good topical tolerance after repeated application on normal mice skin. The therapeutic efficacy of paclitaxel ointment was evaluated with an imiquimod-induced psoriatic model. A significant improvement has been shown both in the phenotypic and histopathological features of psoriatic skin treated with the ointment. There was also a significant reduction in the epidermal thickness compared to the imiquimod group. The findings confirm that the O/O PTX ointment without any surfactant appears to be a promising approach for the treatment of psoriasis.


Assuntos
Paclitaxel/uso terapêutico , Psoríase/tratamento farmacológico , Administração Tópica , Animais , Humanos , Imiquimode/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pomadas , Paclitaxel/administração & dosagem , Tamanho da Partícula , Psoríase/induzido quimicamente , Pele/efeitos dos fármacos , Tensoativos
11.
Gynecol Oncol ; 154(2): 294-301, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31174889

RESUMO

OBJECTIVES: The WNT pathway is an important oncologic driver of epithelial ovarian cancer (EOC). The first-in-class recombinant fusion protein ipafricept (IPA) blocks Wnt signaling through binding of Wnt ligands. This phase Ib trial was designed to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RPh2) for IPA in combination with taxane and platinum therapy (C/P). METHODS: Dose escalation started with a standard 3 + 3 design for IPA/C/P with q3w intravenous IPA on Day 1, in cycles 1 to 6 with C (AUC = 5 mg/ml·min) and P (175 mg/m2). For enhanced bone safety the trial was revised to 6-patient cohorts with a q3w regimen of IPA on Day 1 and C/P on Day 3 (IPA → C/P). RESULTS: 37 patients have been treated; 30 of whom were treated following protocol revision to q3w IPA(D1) → C/P(D3) (2 & 4 mg/kg). IPA-related TEAEs that occurred in ≥15% included: fatigue (40%); nausea (35%); diarrhea and decreased appetite (22%) each; dysgeusia (19%); and vomiting (16.2%). 22% reported ≥1 IPA related TEAE Grade ≥3 the most common of which was neutropenia at 16%. There were no DLTs; the MTD was not reached. The maximum administered dose based on bone safety was 6 mg/kg. The overall response rate (ORR) was 75.7%. Median PFS was 10.3 months (95% CI 8.5-14.2) and OS 33 months (95% CI 23.4-NR). CONCLUSIONS: IPA is well tolerated in combination with sequential C/P. ORR, PFS and OS are comparable to historical data but bone toxicity at efficacy doses of this particular Wnt inhibitor limit further development in EOC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Fragmentos Fc das Imunoglobulinas/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Receptores Acoplados a Proteínas-G/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Idoso , Antineoplásicos Fitogênicos , Osso e Ossos/efeitos dos fármacos , Carboplatina/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Fragmentos Fc das Imunoglobulinas/efeitos adversos , Fragmentos Fc das Imunoglobulinas/farmacologia , Dose Máxima Tolerável , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos , Proteínas Recombinantes de Fusão/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos
13.
Lancet ; 394(10194): 230-239, 2019 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-31204115

RESUMO

BACKGROUND: The optimal technique of percutaneous coronary intervention in patients at high bleeding risk is not known. The hypothesis of the DEBUT trial was that percutaneous coronary intervention with drug-coated balloons is non-inferior to percutaneous coronary intervention with bare-metal stents for this population. METHODS: The DEBUT trial is a randomised, single-blind non-inferiority trial done at five sites in Finland. Patients were eligible if they had an ischaemic de-novo lesion in a coronary artery or bypass graft that could be treated with drug-coated balloons, at least one risk factor for bleeding, and a reference vessel diameter of 2·5-4·0 mm. Those with myocardial infarction with ST-elevation, bifurcation lesions needing a two-stent technique, in-stent restenosis, and flow-limiting dissection or substantial recoil (>30%) of the target lesion after predilation were excluded. After successful predilation of the target lesion, patients were randomly assigned (1:1), by use of a computer-generated random sequence, to percutaneous coronary intervention with a balloon coated with paclitaxel and iopromide or a bare-metal stent. The primary outcome was major adverse cardiac events at 9 months. Non-inferiority was shown if the absolute risk difference was no more than 3%. All prespecified analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01781546. FINDINGS: Between May 22, 2013, and Jan 16, 2017, 220 patients were recruited for the study and 208 patients were assigned to percutaneous coronary intervention with drug-coated balloon (n=102) or bare metal stent (n=106). At 9 months, major adverse cardiac events had occurred in one patient (1%) in the drug-coated balloon group and in 15 patients (14%) in the bare-metal stent group (absolute risk difference -13·2 percentage points [95% CI -6·2 to -21·1], risk ratio 0·07 [95% CI 0·01 to 0·52]; p<0·00001 for non-inferiority and p=0·00034 for superiority). Two definitive stent thrombosis events occurred in the bare metal stent group but no acute vessel closures in the drug-coated balloon group. INTERPRETATIONS: Percutaneous coronary intervention with drug-coated balloon was superior to bare-metal stents in patients at bleeding risk. The drug-coated balloon-only coronary intervention is a novel strategy to treat this difficult patient population. Comparison of this approach to the new generation drug-eluting stents is warranted in the future. FUNDING: B Braun Medical AG, AstraZeneca, and Competitive State Research Funding of the Kuopio University Hospital Catchment Area.


Assuntos
Angioplastia Coronária com Balão/instrumentação , Materiais Revestidos Biocompatíveis , Doença da Artéria Coronariana/terapia , Idoso , Idoso de 80 Anos ou mais , Angioplastia Coronária com Balão/métodos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/patologia , Reestenose Coronária/prevenção & controle , Feminino , Hemorragia/etiologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Método Simples-Cego , Stents , Moduladores de Tubulina/administração & dosagem
14.
Gynecol Oncol ; 154(1): 13-21, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31053405

RESUMO

OBJECTIVES: To determine if the addition of paclitaxel (P) to cisplatin and doxorubicin (CD) following surgical debulking and volume-directed radiation therapy improved long-term, recurrence-free survival (RFS) and overall survival (OS) in patients with advanced-stage endometrial cancer (EC). METHODS: Prospective, randomized GOG trial comparing (CD) (50 mg/m2)/(45 mg/m2) +/- (P) (160 mg/m2) following volume-directed radiation and surgery in advanced EC. A Kaplan-Meier (KM) analysis characterized the relationship between treatment arms and the OS outcome, a log-rank test assessed the independence of treatment with the OS outcome, and the treatment effect on estimated OS was determined using a Cox proportional hazards (PH) model stratified by stage. The PH assumption was assessed using a test of interaction between treatment variable and the natural logarithm of survival time. Adverse events, regardless of attribution, were graded. RESULTS: Since initial publication, 60 deaths occurred, leaving 311 patients alive with 290 (93.8%) recurrence- free. There was no significant decrease in the risk of recurrence or death associated with the CDP treatment regimen stratified for stage (p = 0.14, one-tail). The exploratory analysis for OS and the corresponding homogeneity tests for different effects across subgroups revealed only EFRT and EFRT & GRD status to have significantly different treatment effects (p = 0.027 and p = 0.017, respectively). Second primary malignancies were identified in 17/253 (6.4%) and 19/263 (7.0%) of patients treated with CD and CDP respectively. Breast (2.4%) followed by colon (1%) were the two cancers most frequently diagnosed in this setting. CONCLUSION: No significant difference between treatment arms was identified. Subgroup analysis both in the initial and current reports demonstrated a trend towards improved RFS and OS in patients treated with CDP and EFRT. This long-term analysis of outcomes also identified the necessity of providing on-going cancer screening to patients enrolled in trials.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Estudos Prospectivos , Salpingo-Ooforectomia , Taxa de Sobrevida , Adulto Jovem
15.
Gynecol Oncol ; 154(1): 138-143, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31079832

RESUMO

OBJECTIVE: To evaluate hematologic adverse effect profiles associated with frontline platinum-based chemotherapy in ovarian cancer patients according to BRCA 1/2 mutational status. METHODS: Patients with high-grade serous ovarian cancer and a known BRCA mutational status who received in frontline 6 cycles of Carboplatin (AUC 5) plus Paclitaxel 175 mg/mq were retrospectively selected from our databases. Hematologic toxicity profiles of BRCA mutated patients were compared to non-mutated patients, according to EORTC Common Terminology Criteria for Adverse Events (CTCAE_4.02). RESULTS: Totally, 176 women of whom 58 (33%) were BRCA1/2 mutation carriers - 40 BRCA1 (69%) and 18 (31%) BRCA2 mutations carriers - and 118 (67%) non-carriers were identified. A significant higher frequency of thrombocytopenia (24% vs 5%; p < 0.001), anemia (21% vs 7%; p = 0.006) and neutropenia (62% vs 27%; p ≤0.001) was observed in BRCA mutated patients, resulting in a higher percentage of granulocyte-colony stimulating growth factors injection (12% versus 1%, p < 0.001) and dose delay (19% versus 27%, p = 0.005). The multivariate analysis confirmed that granulocyte-colony stimulating growth factors injection and dose delay were statistically significantly more frequent in BRCA mutated patients (OR 2.567, 95% CI 1.136-5.798, p = 0.035; OR 3.860, 95% CI 1.098-13.570, p = 0.023). Finally, the total number of hematologic adverse events compared between the two groups of patients during the entire treatment period showed a substantial higher rate of hematologic adverse events in BRCA mutated population. CONCLUSIONS: Germline BRCA 1/2 mutations are associated with a higher hematologic toxicity in patients with ovarian cancer who underwent platinum-based chemotherapy.


Assuntos
Cistadenocarcinoma Seroso/tratamento farmacológico , Genes BRCA1 , Genes BRCA2 , Mutação em Linhagem Germinativa , Doenças Hematológicas/induzido quimicamente , Doenças Hematológicas/genética , Neoplasias Ovarianas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteína BRCA1/genética , Proteína BRCA2/genética , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Estudos de Coortes , Cistadenocarcinoma Seroso/sangue , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patologia , Feminino , Predisposição Genética para Doença , Doenças Hematológicas/sangue , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Estudos Retrospectivos
16.
Gynecol Oncol ; 154(1): 22-28, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31109659

RESUMO

OBJECTIVE: To identify the optimal adjuvant treatment regimen for patients with endometrioid and non-endometrioid node-positive endometrial cancer. METHODS: We retrospectively identified 249 women with FIGO 2009 stage IIIC endometrial cancer at our institution who underwent surgical staging from 1985 to 2015 followed by external beam radiotherapy (RT), chemotherapy (CT), or a combination of CT + RT. Survival rates were calculated using the Kaplan-Meier method. RESULTS: The 5-year disease-specific survival (DSS) rate for all patients was 65%. Adjuvant CT + RT conferred higher rates of 5-year DSS as compared to CT alone in patients with grade 3 endometrioid and non-endometrioid tumors (61% vs. 27%, P = 0.04 and 67% vs. 38%, P = 0.02, respectively). Among patients with non-endometrioid tumors, treatment with concurrent chemoradiotherapy followed by additional sequential chemotherapy had higher 5-year DSS rates than with concurrent chemoradiotherapy alone (74% vs. 50%, P = 0.02). The 3-year pelvic recurrence rate was 5% with RT ±â€¯CT and 35% with CT alone (P < 0.001) for all patients. No paraaortic nodal failures were observed following extended-field RT, but 14% of patients who received pelvic-only RT or CT alone developed recurrences in the paraaortic nodes (P < 0.001). CONCLUSIONS: Combined-modality therapy including adjuvant external beam pelvic radiotherapy yields excellent outcomes for patients with all subtypes of node-positive endometrial cancer. The most pronounced DSS advantage from adjuvant chemoradiotherapy was evident in women with non-endometrioid endometrial cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Endometrioide/terapia , Cisplatino/uso terapêutico , Neoplasias do Endométrio/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carboplatina/administração & dosagem , Carcinoma Endometrioide/patologia , Quimiorradioterapia Adjuvante , Neoplasias do Endométrio/patologia , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
17.
J Cardiovasc Surg (Torino) ; 60(4): 433-438, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31058479

RESUMO

When the FDA approved the use of a paclitaxel-coated stent in the peripheral arteries in November of 2012, a new era in the treatment of peripheral arterial disease (PAD) emerged. This marked, for the first time in the United States, that a drug-eluting device was available to treat this complex arterial bed, and has likely changed forever how PAD is treated. Prior to this, US physicians had been using drug-eluting stents (DES) in the coronary arteries for 8 years with exceptional results in both safety and efficacy. Since the Zilver®PTX® (Cook Medical, Bloomington, IN USA) was released, multiple drug-coated balloons (DCB) with paclitaxel have been approved in the US, as has another DES, the Eluvia™ stent (Boston Scientific, Minneapolis, MN USA).


Assuntos
Angioplastia com Balão/instrumentação , Stents Farmacológicos , Paclitaxel/administração & dosagem , Doença Arterial Periférica/terapia , Aprovação de Equipamentos , Stents Farmacológicos/efeitos adversos , Humanos , Paclitaxel/efeitos adversos , Paclitaxel/farmacocinética , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/cirurgia , Desenho de Prótese , Ensaios Clínicos Controlados Aleatórios como Assunto , Estados Unidos , United States Food and Drug Administration
18.
J Cardiovasc Surg (Torino) ; 60(4): 439-449, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31062571

RESUMO

Drug-eluting stent (DES) are the mainstay therapy for the treatment of coronary artery disease. Stent design and drug-elution strategies have evolved over the years leading to the last generation DES which shows optimal safety and efficacy outcome. Peripheral arteries have different mechanical and biological features and the lessons learned from the coronary field have been difficult to introduce into the development of peripheral vascular technologies. First, due to its complex biomechanical behavior the use of metallic stents is limited in some vascular segments (i.e., distal superficial fermoral artery [SFA]). Also, peripheral vascular atherosclerosis is different containing higher levels of plaque burden and calcium. Finally, peripheral arterial disease tends to be more aggressive including longer lesions and higher incidence of total chronic occlusion. In general terms, restenosis in the peripheral vascular territory is more aggressive and occurs at a later time (~12 months) requiring a different pharmacokinetic profile compared to coronary technologies. Several strategies have been evaluated in the peripheral arteries raging from the bare metal stent to the drug coated balloon and drug eluting stent with outcome varying depending on the different field of application (i.e. SFA and below-the-knee). Results coming from the clinical trial are encouraging but further studies and direct comparison among the different technologies are demanded to determine the best therapy for peripheral vascular disease.


Assuntos
Paclitaxel/administração & dosagem , Doença Arterial Periférica/terapia , Sirolimo/administração & dosagem , Stents , Sistemas de Liberação de Medicamentos , Stents Farmacológicos , Everolimo/administração & dosagem , Artéria Femoral/cirurgia , Humanos , Doença Arterial Periférica/tratamento farmacológico , Polímeros , Prevenção Secundária/métodos , Serina-Treonina Quinases TOR/antagonistas & inibidores
19.
Asian Pac J Cancer Prev ; 20(4): 1199-1206, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31030495

RESUMO

Objective: Despite advanced treatment options available, drug resistance develops in breast cancer (BC) patients requiring novel effective drugs. Stylissa carteri, a marine sponge predominantly living in Indonesia territories, has not been extensively studied as anti-cancer. Therefore, this study targeted to assess the anti-tumor activity of the ethanol extract of S. carteri in BC cells. Methods: S. carteri was collected from Pramuka Island, at Kepulauan Seribu National Park, Jakarta, Indonesia and extracted using ethanol. Different BC cells including MDA MB 231, MDA MB 468, SKBR3, HCC-1954 and MCF-7 cells were treated with this extract for cytotoxic analysis using MTT assay. Spheroid growth assay and apoptosis assay were conducted in HCC-1954 cells. In addition, cell migration analysis and synergistic activity with doxorubicin or paclitaxel were conducted in MDA MB 231 cells. This extract was subjected also for GC-MS analysis. Results: The results show that ethanol extract of S. carteri demonstrated a cytotoxic activity in BC cells. The IC50 of this extract was lower 15 µg/ml in MDA MB 231, MDA MB 468, SKBR3, and HCC-1954 cells. Moreover, this extract inhibited spheroids growth and induced apoptosis in HCC-1954 cells. It inhibited cell migration and demonstrated a synergistic activity with doxorubicin or paclitaxel on triggering cell death in MDA MB 231 cells. Furthermore, GC-MS analysis indicated that this extract contained 1,2-Benzenediol, Dibutyl phthalate and 9,12-Octadecadienoic acid, ethyl ester. Conclusion: Our preliminary data indicate a potential anti-tumor activity of ethanol extract of S. carteri in breast cancer cells.


Assuntos
Alcaloides/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Etanol/química , Poríferos/química , Alcaloides/isolamento & purificação , Animais , Apoptose , Neoplasias da Mama/tratamento farmacológico , Movimento Celular , Doxorrubicina/administração & dosagem , Feminino , Humanos , Paclitaxel/administração & dosagem , Células Tumorais Cultivadas
20.
Oncol Rep ; 41(6): 3155-3166, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31002367

RESUMO

Baker's yeast, Saccharomyces cerevisiae, has been shown to sensitize a variety of breast cancer cell (BCC) lines to paclitaxel chemotherapy in vitro. The present study evaluated the ability of S. cerevisiae to sensitize BCCs to paclitaxel in animals bearing Ehrlich ascites carcinoma (EAC). Mice bearing EAC were intratumorally injected with dead S. cerevisiae (1x107 cells/ml) in the presence or absence of low- and high-dose paclitaxel [paclitaxel-L, 2 mg/kg body weight (BW) and paclitaxel-H, 10 mg/kg BW, respectively]. At 30 days post tumor inoculation, co-treatment with yeast plus paclitaxel-L showed improvements over paclitaxel-H alone, as measured by tumor weight (-64 vs. -53%), DNA damage (+79 vs. +62%), tumor cell apoptosis (+217 vs. +177%), cell proliferation (-56 vs. -42%) and Ki-67 marker (+95 vs. +40%). Histopathology and ultra-structural examinations showed that yeast plus paclitaxel-L enhanced apoptosis in EAC more than paclitaxel-H alone and caused comparable tumor necrosis. We conclude that baker's yeast may be used with low-dose chemotherapy to achieve the same potency as high-dose chemotherapy in mice bearing EAC. This suggests that baker's yeast may be an anticancer adjuvant and may have clinical implications for the treatment of breast cancer.


Assuntos
Adenocarcinoma/tratamento farmacológico , Carcinoma de Ehrlich/tratamento farmacológico , Neoplasias Mamárias Animais/tratamento farmacológico , Saccharomyces cerevisiae/química , Adenocarcinoma/patologia , Animais , Apoptose/efeitos dos fármacos , Carcinoma de Ehrlich/genética , Carcinoma de Ehrlich/patologia , Proliferação de Células/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Dieta , Feminino , Humanos , Células MCF-7 , Neoplasias Mamárias Animais/patologia , Camundongos , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Carga Tumoral/efeitos dos fármacos
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