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1.
Lancet Oncol ; 23(5): 650-658, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35421369

RESUMO

BACKGROUND: Recurrence is common after neoadjuvant chemotherapy and radical treatment for muscle-invasive bladder cancer. We investigated the effect of adding nintedanib to neoadjuvant chemotherapy on response and survival in muscle-invasive bladder cancer. METHODS: NEOBLADE was a parallel-arm, double-blind, randomised, placebo-controlled, phase 2 trial of neoadjuvant gemcitabine and cisplatin chemotherapy with nintedanib or placebo in locally advanced muscle-invasive bladder cancer. Patients aged 18 years or older, with an Eastern Cooperative Oncology Group performance status of 0-1, were recruited from 15 hospitals in the UK. Patients were randomly assigned (1:1) to nintedanib or placebo using permuted blocks with random block sizes of two or four, stratified by centre and glomerular filtration rate. Treatments were allocated using an interactive web-based system, and patients and investigators were masked to treatment allocation throughout the study. Patients received oral nintedanib (150 mg or 200 mg twice daily for 12 weeks) or placebo, in addition to usual neoadjuvant chemotherapy with intravenous gemcitabine 1000 mg/m2 on days 1 and 8 and intravenous cisplatin 70 mg/m2 on day 1 of a 3-weekly cycle. The primary endpoint was pathological complete response rate, assessed at cystectomy or at day 8 of cyclde 3 (plus or minus 7 days) if cystectomy did not occur. Primary analyses were done in the intention-to-treat population. The trial is registered with EudraCT, 2012-004895-01, and ISRCTN, 56349930, and has completed planned recruitment. FINDINGS: Between Dec 4, 2014, and Sept 3, 2018, 120 patients were recruited and were randomly allocated to receive nintedanib (n=57) or placebo (n=63). The median follow-up for the study was 33·5 months (IQR 14·0-44·0). Pathological complete response in the intention-to-treat population was reached in 21 (37%) of 57 patients in the nintedanib group and 20 (32%) of 63 in the placebo group (odds ratio [OR] 1·25, 70% CI 0·84-1·87; p=0·28). Grade 3 or worse toxicities were observed in 53 (93%) of 57 participants who received nintedanib and 50 (79%) of 63 patients in the placebo group (OR 1·65, 95% CI 0·74-3·65; p=0·24). The most common grade 3 or worse adverse events were thromboembolic events (17 [30%] of 57 patients in the nintedanib group vs 13 [21%] of 63 patients in the placebo group [OR 1·63, 95% CI 0·71-3·76; p=0·29]) and decreased neutrophil count (22 [39%] in the nintedanib group vs seven [11%] in the placebo group [5·03, 1·95-13·00; p=0·0006]). 45 treatment-related serious adverse events occurred in the nintedanib group and 43 occurred in the placebo group. One treatment-related death occurred in the placebo group, which was due to myocardial infarction. INTERPRETATION: The addition of nintedanib to chemotherapy was safe but did not improve the rate of pathological complete response in muscle-invasive bladder cancer. FUNDING: Boehringer Ingelheim.


Assuntos
Cisplatino , Neoplasias da Bexiga Urinária , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/efeitos adversos , Desoxicitidina/análogos & derivados , Método Duplo-Cego , Feminino , Humanos , Indóis , Masculino , Músculos , Terapia Neoadjuvante/efeitos adversos , Neoplasias da Bexiga Urinária/tratamento farmacológico
2.
BMC Cancer ; 22(1): 462, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35477432

RESUMO

BACKGROUND: Long course radiotherapy plus neoadjuvant chemotherapy followed by resection (total mesorectal excision, TME) has accepted widespread recognized in the treatment of locally advanced rectal cancer (LARC). Tislelizumab, an anti-PD1 humanized IgG4 monoclonal antibody, has been demonstrated with clinical activity and is approved for treating recurrent/refractory classical Hodgkin lymphoma and locally advanced/metastatic urothelial carcinoma in China. However, the safety and efficacy of long course (neoadjuvant chemoradiotherapy, NCRT) plus tislelizumab followed by TME for LARC is still uncertain. METHODS: This NCRT-PD1-LARC trial will be a prospective, multicenter and phase II clinical trial designed to evaluate the safety and efficacy of LARC patients treated with long course NCRT plus tislelizumab followed by TME. This trial will consecutively enroll 50 stage II/III LARC patients (cT3N0M0 and cT1-3N1-2M0) with the tumor distal location ≤ 7 cm from anal verge at 7 centers in China. The enrolled patients will receive long course radiotherapy (50 Gy/25 f, 2 Gy/f, 5 days/week) and three 21-day cycles capecitabine (1000 mg/m2, bid, po, day1-14) plus three 21-day cycles tislelizumab (200 mg, iv.gtt, day8), followed by TME 6-8 weeks after the end of radiotherapy. The primary efficacy endpoint will be the pathological complete response (pCR) rate, which is defined as absence of viable tumor cells in the primary tumor and lymph nodes. DISCUSSION: To our knowledge, this trial is the first multicenter clinical trial in China to assess the safety and efficacy of NCRT plus anti-PD1 therapy followed by TME to treat patients with LARC. NCRT followed by TME was recognized as the most recommended treatment against LARC while could not be completely satisfied in clinic. This study expects to provide a solid basis and encouraging outcomes for this promising combination of radiotherapy, chemotherapy and immunotherapy in LARC. TRIAL REGISTRATION: Name of the registry: ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: NCT04911517. Date of registration: 23 May 2021. URL of trial registry record: https://www. CLINICALTRIALS: gov/ct2/show/NCT04911517?id=BFH-NCRTPD&draw=2&rank=1 .


Assuntos
Terapia Neoadjuvante , Segunda Neoplasia Primária , Neoplasias Retais , Anticorpos Monoclonais Humanizados , Carcinoma de Células de Transição , Ensaios Clínicos Fase II como Assunto , Feminino , Humanos , Masculino , Estudos Multicêntricos como Assunto , Terapia Neoadjuvante/efeitos adversos , Segunda Neoplasia Primária/terapia , Estudos Prospectivos , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Neoplasias da Bexiga Urinária
3.
Clin Nutr ; 41(5): 1112-1121, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35413573

RESUMO

BACKGROUND & AIMS: Established supportive care to reduce the toxicity of neoadjuvant chemotherapy (NAC) is lacking. This multicenter randomized study compared the administration of synbiotics combined with enteral nutrition (EN) versus that of prophylactic antibiotics as supportive care treatment for patients with esophageal cancer undergoing NAC. METHODS: Patients with advanced esophageal cancer scheduled to receive NAC were randomly administered either prophylactic antibiotics (antibiotic group) or synbiotics combined with EN (Syn + EN group). The primary endpoint was the febrile neutropenia (FN) incidence during the first course, and the secondary endpoints were other adverse events, changes in intestinal environment, including fecal microbiota, organic acid concentrations, pH, and chemotherapy tolerability. RESULTS: Eighty-one patients were enrolled. The FN incidence was nonsignificantly lower (P = 0.088) in the Syn + EN group. The incidences of grade 4 neutropenia and grades 2-4 diarrhea were significantly lower in the Syn + EN group (P = 0.014 and 0.033, respectively). Relative dose intensity was significantly higher in the Syn + EN group (92.0 ± 10.9%) than in the antibiotic group (83.2 ± 18.2%) (P = 0.01). Alpfa diversity was significantly higher in the Syn + EN group than in the antibiotic after chemotherapy (P = 0.002). The numbers of Bifidobacterium (P < 0.05), Lacticaseibacillus (P < 0.001), and Enterobacteriaceae (P < 0.001) and the concentration of acetic acid (P < 0.001) were significantly higher in the Syn + EN group than in the antibiotic group after chemotherapy. The severity of diarrhea and occurrence of FN were significantly correlated with Clostridioides difficile abundance and were significantly inversely correlated with acetic acid concentration after chemotherapy. CONCLUSIONS: Synbiotics combined with EN may be an alternative supportive care treatment to prophylactic antibiotics in patients with cancer undergoing toxic chemotherapy (https://jrct.niph.go.jp; jRCTs051180153).


Assuntos
Neoplasias Esofágicas , Neutropenia , Simbióticos , Antibacterianos/efeitos adversos , Diarreia/etiologia , Nutrição Enteral , Neoplasias Esofágicas/tratamento farmacológico , Humanos , Terapia Neoadjuvante/efeitos adversos , Neutropenia/etiologia
4.
Front Immunol ; 13: 848881, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35371089

RESUMO

Background: Immunotherapy has become a pillar of advanced solid tumors treatment. Patients are more likely to benefit from neoadjuvant immunotherapy compared with traditional neoadjuvant therapy. However, the safety and efficacy of neoadjuvant immunotherapy for the treatment of locally advanced, surgically resectable Esophageal squamous cell carcinoma (ESCC) remain unknown. Method: ESCC patients who received neoadjuvant treatment following minimally invasive esophagogastrostomy were enrolled from June 2020 to September 2021. The characteristics of neoadjuvant treatment and surgery were investigated to determine the safety and efficacy of the neoadjuvant combination of chemotherapy and immunotherapy (NCI). Results: A total of 149 patients were included in the study. Patient ratio was 40:109 between NCI and neoadjuvant chemotherapy plus radiotherapy (NCR) groups. No significant difference was found in terms of pathological characteristics, including ypN stage, ypTNM stage, differentiation, lymphovascular invasion, perineural invasion, pathological complete regression and tumor regression score, and these parameters were not correlated with NCI or NCR (all p>0.05). Regarding to the operation, the NCI group had less blood loss (49.25 ± 13.47 vs. 57.02 ± 47.26, p<0.001), and shorter operation time (247.75 ± 28.28 vs. 285.83 ± 52.43, p<0.001) than the NCR group. Additionally, the NCI group demonstrated a lower rate of overall perioperative complications (p=0.003) and grade >2 perioperative complications (p=0.042) than the NCR group. Conclusion: Overall, the findings reported here indicate NCI could result in better outcome and less complications to locally advanced ESCC patients compared with NCR therapy. As a novel therapeutic option, the efficacy and safety of NCI appears to be feasible and safe, while long-term survival data is still needed.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/terapia , Esofagectomia/efeitos adversos , Humanos , Imunoterapia , Terapia Neoadjuvante/efeitos adversos
5.
Oncologist ; 27(1): e18-e28, 2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-35305102

RESUMO

INTRODUCTION: Immune checkpoint inhibitors (ICIs) are effective in the treatment of advanced esophageal squamous cell carcinoma (ESCC); however, their efficacy in locally advanced resectable ESCC and the potential predictive biomarkers have limited data. METHODS: In this study, locally advanced resectable ESCC patients were enrolled and received neoadjuvant toripalimab (240 mg, day 1) plus paclitaxel (135 mg/m2, day 1) and carboplatin (area under the curve 5 mg/mL per min, day 1) in each 3-week cycle for 2 cycles, followed by esophagectomy planned 4-6 weeks after preoperative therapy. The primary endpoints were safety, feasibility, and the major pathological response (MPR) rate; the secondary endpoints were the pathological complete response (pCR) rate, disease-free survival (DFS), and overall survival (OS). Association between molecular signatures/tumor immune microenvironment and treatment response was also explored. RESULTS: Twenty resectable ESCC patients were enrolled. Treatment-related adverse events (AEs) occurred in all patients (100%), and 4 patients (22.2%) experienced grade 3 or higher treatment-related AEs. Sixteen patients underwent surgery without treatment-related surgical delay, and the R0 resection rate was 87.5% (14/16). Among the 16 patients, the MPR rate was 43.8% (7/16) and the pCR rate was 18.8% (3/16). The abundance of CD8+ T cells in surgical specimens increased (P = .0093), accompanied by a decreased proportion of M2-type tumor-associated macrophages (P = .036) in responders upon neoadjuvant therapy. Responders were associated with higher baseline gene expression levels of CXCL5 (P = .03) and lower baseline levels of CCL19 (P = .017) and UMODL1 (P = .03). CONCLUSIONS: The combination of toripalimab plus paclitaxel and carboplatin is safe, feasible, and effective in locally advanced resectable ESCC, indicating its potential as a neoadjuvant treatment for ESCC. CLINICAL TRIAL REGISTRATION: NCT04177797.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/farmacologia , Carboplatina/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Humanos , Terapia Neoadjuvante/efeitos adversos , Paclitaxel , Microambiente Tumoral
6.
Oper Neurosurg (Hagerstown) ; 22(4): 208-214, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35234410

RESUMO

BACKGROUND: Postoperative stereotactic radiosurgery after resection of brain metastases is currently the standard of care. However, rates of leptomeningeal disease (LMD) after postoperative stereotactic radiosurgery have been reported to be >30%. Neoadjuvant stereotactic radiosurgery (NaSRS) has been proposed as an alternative treatment approach to decrease this risk. OBJECTIVE: To report the local control (LC) and LMD rates in patients undergoing NaSRS. METHODS: Our retrospective multicenter case series included consecutive patients planned for SRS followed by resection of intracranial lesions with a confirmed primary malignancy. Concurrent SRS alone to other intracranial lesions was permitted. Exclusion criteria included previous local treatment to that particular lesion and Eastern Cooperative Oncology Group performance status ≥3. Outcomes reported included LC, distant intracranial control (DC), overall survival, LMD, and radionecrosis (RN) rates. RESULTS: Overall, 28 patients with 29 lesions were eligible for analysis. The median follow-up was 12.8 months. The mean age was 62.5 (range 43-80) years, and 55% were Eastern Cooperative Oncology Group performance status 0 to 1. The most common primary malignancies included non-small cell lung cancer (43%) and melanoma (32%). Hypofractionated SRS was used in 62.1%. The 12-month LC and LMD rates were 91.3% and 4.0%, respectively. The 12-month RN, DC, and overall survival rates were 5.0%, 51.5%, and 60.1%, respectively. CONCLUSION: Compared with postoperative SRS, our study suggests that NaSRS leads to comparable local control with a decreased risk of LMD and RN. This is the first NaSRS series with a majority of patients treated with fractionated SRS. NaSRS is a promising approach for appropriate patients where surgical resection is a component of local therapy.


Assuntos
Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Neoplasias Meníngeas , Radiocirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/secundário , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Neoplasias Meníngeas/cirurgia , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
7.
Gastric Cancer ; 25(3): 619-628, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35254550

RESUMO

BACKGROUND: Nivolumab monotherapy has demonstrated superior efficacy in advanced unresectable gastric cancer (GC), but its impact on resectable GC remains unknown. This phase I study aimed to evaluate safety, feasibility, and potential biomarkers of neoadjuvant nivolumab monotherapy in resectable GC. METHODS: Untreated, resectable, cT2 or more advanced gastric adenocarcinomas with clinical stage I, II, or III were treated with two doses of nivolumab before gastrectomy. Patients were excluded if their tumors may be applicable to neoadjuvant chemotherapy. The primary endpoint was the incidence of adverse event (AE) categories of special interest. RESULTS: All of the 31 enrolled patients completed 2 doses of nivolumab monotherapy. While 30 (97%) patients underwent surgery with curative intent, 1 patient discontinued before the planned surgical intervention because of a newly emerging liver metastasis. Seven patients (23%) had nivolumab treatment-related AEs, and one patient had a treatment-related AE of grade 3-4. The incidences of treatment-related AE categories of special interest ranged from 0 to 6%. Notable surgical complications included two cases of grade 3 anastomotic leakage and two cases of pancreatic fistula. The major pathologic response (MPR) assessed by the independent pathology review committee was achieved in five (16%) patients, of which one patient had a pathologic complete response. The MPR was mostly observed in patients with positive PD-L1 expression, high microsatellite instability, and/or high tumor mutation burden. CONCLUSIONS: Neoadjuvant nivolumab monotherapy is feasible with an acceptable safety profile and induces a MPR in certain patients with resectable GC. (Registration: clinicaltrials.jp, JapicCTI-183895).


Assuntos
Adenocarcinoma , Nivolumabe , Neoplasias Gástricas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Humanos , Instabilidade de Microssatélites , Terapia Neoadjuvante/efeitos adversos , Nivolumabe/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia
8.
PLoS One ; 17(3): e0266001, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35324998

RESUMO

This study aimed to assess neoadjuvant chemotherapy's clinical outcomes such as efficacy, toxicity, and survival outcomes followed by radical hysterectomy ((NACT-RS) among women with cervical cancer stage IB3 and IIA2, by comparing concurrent chemoradiotherapy (CCRT) and NACT-RS. The study retrospectively reviewed patients with (2018 FIGO) stage IB3 and IIA2 cervical cancer who received preoperative neoadjuvant chemotherapy followed by NACT-RS or concurrent chemoradiotherapy (CCRT). The outcome measures were the 5-year survival and complication rates between the two groups. The median follow-up was 75 months. In total, 218 patients had stage IIA2, 136 patients had stage IB3, 201 patients received CCRT, and 153 patients received preoperative NACT-RS. In the CCRT group, the incidence of early complications (myelosuppression, gastrointestinal and urinary) was higher compared with that in the NACT-RS group (76.1 vs. 26.1%; p < 0.001, respectively). There was no significant difference between the two study groups concerning late complications. Five-year PFS was 79.9% and 85.5% in the NACT-RS and CCRT groups, respectively (p = 0.093). Five-year OS was 86.9% and 85.5% in the NACT-RS and CCRT groups, respectively (p = 0.97). In the multivariate clinicopathologic characteristics analysis for OS, initial tumor size > 4.3 cm (HR 5.11; p < 0.001), AC/ASC (HR 1.89; p = 0.02), histologic grade 2-3 (HR 2.25; p = 0.04), and 2018 FIGO stage IIA2 (HR 8.67; p < 0.001) were independent risk factors. The survival of patients with stage IB3 and IIA2 cervical cancer treated with NACT-RS was similar to that of patients treated with CCRT without increasing side effects.


Assuntos
Terapia Neoadjuvante , Neoplasias do Colo do Útero , Quimiorradioterapia/efeitos adversos , Feminino , Humanos , Histerectomia , Masculino , Terapia Neoadjuvante/efeitos adversos , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia
9.
J Am Coll Surg ; 234(4): 436-443, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35290262

RESUMO

BACKGROUND: The introduction of more effective chemotherapy a decade ago has led to increased use of neoadjuvant therapy (NAT) in patients with pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to assess the evolving use of NAT in individuals with PDAC undergoing pancreatoduodenectomy (PD) and to compare their outcomes with patients undergoing upfront operation. STUDY DESIGN: The American College of Surgeons NSQIP Procedure Targeted Pancreatectomy database was queried from 2014 to 2019. Patients undergoing pancreatoduodenectomy were evaluated based on the use of NAT versus upfront operation. Multivariable analysis was performed to determine the effect of NAT on postoperative outcomes, including the composite measure optimal pancreatic surgery (OPS). Mann-Kendall trend tests were performed to assess the use of NAT and associated outcomes over time. RESULTS: A total of 13,257 patients were identified who underwent PD for PDAC between 2014 and 2019. Overall, 33.6% of patients received NAT. The use of NAT increased steadily from 24.2% in 2014 to 42.7% in 2019 (p < 0.0001). On multivariable analysis, NAT was associated with reduced serious morbidity (odds ratio [OR] 0.83, p < 0.001), clinically relevant pancreatic fistulas (OR 0.52, p < 0.001), organ space infections (OR 0.74, p < 0.001), percutaneous drainage (OR 0.73, p < 0.001), reoperation (OR 0.76, p = 0.005), and prolonged length of stay (OR 0.63, p < 0.001). OPS was achieved more frequently in patients undergoing NAT (OR 1.433, p < 0.001) and improved over time in patients receiving NAT (50.7% to 56.6%, p < 0.001). CONCLUSION: NAT before pancreatoduodenectomy increased more than 3-fold over the past decade and was associated with improved optimal operative outcomes.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/etiologia , Carcinoma Ductal Pancreático/cirurgia , Humanos , Terapia Neoadjuvante/efeitos adversos , Pancreatectomia/efeitos adversos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos
10.
Technol Cancer Res Treat ; 21: 15330338221086085, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35296187

RESUMO

Background: A retrospective evaluation of tolerance and efficacy of two schemes of neoadjuvant treatment in patients (pts) with unresectable rectal cancer: radiochemotherapy (CRT) and radiotherapy (RT), including conventional and accelerated hyperfractionation. Material and Method: A total of 145 consecutive pts with unresectable, locally advanced rectal cancer. The schemes used are RT in 73 (50%) or CRT in 72 (50%). In CRT, 54 Gy in 1.8 Gy fractions was given with chemotherapy, In the RT group, conventional fractionation (CFRT) and hyperfractionated accelerated radiotherapy (HART). HART was introduced at first as an alternative to CFRT, after radiobiological studies suggesting a therapeutic gain of hyperfractionation in other cancers, and second to administer relatively high dose needed in unresectable cancer, which is not feasible in hypofractionation because of critical organs sensitivity to high fraction doses (fd). HART was an alternative option in pts with medical contraindications to chemotherapy and to shorten overall treatment time with greater radiobiological effectiveness than CFRT. Results: Objective response (OR) in the RT and CRT group was 60% versus 75%. Resection rate (RR) in RT and CRT: 37% versus 65%. Tumor mobility and laparotomy-based unresectability were significant factors for OR. Performance status (PS), tumor mobility, and neoadjuvant treatment method were significant for RR.


Assuntos
Neoplasias Retais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/efeitos adversos , Fracionamento da Dose de Radiação , Humanos , Terapia Neoadjuvante/efeitos adversos , Neoplasias Retais/patologia , Neoplasias Retais/radioterapia , Estudos Retrospectivos
11.
Eur J Cancer ; 166: 300-308, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35337692

RESUMO

BACKGROUND: Besides their development as additional adjuvant treatments, CDK4/6 inhibitors combined with endocrine therapy could represent less toxic alternatives to chemotherapy in postmenopausal women with high-risk oestrogen receptor-positive, HER2-negative breast cancer currently a candidate for chemotherapy. The multicentre, international, randomised phase 2 NEOPAL trial showed that the letrozole-palbociclib combination led to clinical and pathological responses equivalent to sequential anthracycline-taxanes chemotherapy. Secondary objectives included survival outcomes. METHODS: Secondary end-points of NEOPAL included progression-free survival (PFS) and invasive-disease free survival (iDFS) in the intent-to-treat population. Exploratory end-points were overall survival (OS) and breast cancer specific survival (BCSS) in the intent-to-treat population, as well as iDFS, OS and BCSS according to the administration of chemotherapy. RESULTS: Hundred and six patients were randomised. Pathological complete response rates were 3.8% and 5.9%. Twenty-three of the 53 patients in the letrozole-palbociclib arm received postoperative adjuvant chemotherapy. At a median follow-up of 40.4 months [0-56.6], 11 progressions have been observed, of which three were in the letrozole-palbociclib and 8 in the control arm. PFS (HR = 1.01; [95%CI 0.36-2.90], p = 0.98) and iDFS (HR = 0.83; [95%CI 0.31-2.23], p = 0.71) did not differ between both arms. The 40 months PFS rate was 86.7% [95%CI 78.0-96.4] and 89.9% [95%CI 81.8-98.7] in letrozole-palbociclib and control arms, respectively. Outcomes of patients who did not receive chemotherapy were not statistically different from those who received it. CONCLUSIONS: NEOPAL suggests that a neoadjuvant letrozole-palbociclib strategy may allow sparing chemotherapy in some patients with luminal breast cancer while allowing good long-term outcomes. Larger confirmatory studies are needed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Humanos , Letrozol , Terapia Neoadjuvante/efeitos adversos , Piperazinas , Piridinas , Receptor ErbB-2 , Receptores de Estrogênio , Análise de Sobrevida
12.
Investig Clin Urol ; 63(2): 168-174, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35244990

RESUMO

PURPOSE: To assess the safety and efficacy of gemcitabine and cisplatin as neoadjuvant chemotherapy followed by selective bladder preservation chemoradiotherapy in muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: Patients with clinical T2-T4aN0M0 MIBC eligible for radical cystectomy and cisplatin-based chemotherapy were treated with gemcitabine 1,000 mg/m² on days 1, 8 and 15, and cisplatin 70 mg/m² on day 1 every 28 days for 3 cycles. After clinical re-staging with computed tomography scans and cystoscopy, patients with clinical complete response (CR) were eligible to proceed without cystectomy and receive bladder preservation chemoradiotherapy involving weekly cisplatin 10 mg/m² and up to 70.2 Gy of radiation. The primary endpoint of the present prospective phase II study was metastasis-free survival (MFS). RESULTS: Between Oct 2017 and Nov 2019, a total of 138 MIBC patients were enrolled and treated with neoadjuvant gemcitabine/cisplatin. Neoadjuvant chemotherapy was well-tolerated, with fatigue, nausea, and pruritus being the most commonly observed adverse events. After completion of planned neoadjuvant chemotherapy, 54 patients with a clinical CR and 10 patients who did not have CR but refused surgery received bladder preservation chemoradiotherapy. With a median follow-up duration of 34 months (95% confidence interval [CI], 32%-36%), the 3-year MFS rate in 64 chemoradiotherapy patients was calculated to be 70% (95% CI, 58%-82%). CONCLUSIONS: Neoadjuvant chemotherapy followed by selective bladder preservation chemoradiotherapy based on the clinical CR was feasible and efficacious in the treatment of MIBC.


Assuntos
Carcinoma de Células de Transição , Terapia Neoadjuvante , Neoplasias da Bexiga Urinária , Carcinoma de Células de Transição/terapia , Quimiorradioterapia , Cisplatino , Desoxicitidina/análogos & derivados , Feminino , Humanos , Masculino , Músculos , Terapia Neoadjuvante/efeitos adversos , Estudos Prospectivos , Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/terapia
13.
Eur J Cancer ; 165: 157-168, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35235873

RESUMO

PURPOSE: Panphila evaluated pyrotinib plus trastuzumab, docetaxel and carboplatin as neoadjuvant therapy for early breast cancer (BC), and investigated the predictive role of immune cell subpopulations. PATIENTS AND METHODS: In this multicentre phase 2 study, patients with human epidermal growth factor receptor 2-positive, stage T2-3N0-3M0 BC received pyrotinib 400 mg once daily plus docetaxel (75 mg/m2, day 1), carboplatin (6 mg/mL/min, day 1) and trastuzumab (8 mg/kg loading dose and 6 mg/kg maintenance dose, day 1) for 6 cycles of 21 days each. Simon's 2-stage design was adopted. The primary end-point was pathological complete response (pCR, ypT0/is ypN0) rate. Tumour-infiltrating lymphocytes (TILs) were assessed by haematoxylin and eosin staining and multiplex immunohistochemistry. RESULTS: In the modified intention-to-treat population (n = 69), 38 patients (55.1%) achieved pCR. In the safety population (n = 74), the most common grade ≥3 adverse events were diarrhoea (43.2%), anaemia (37.8%), vomiting (16.2%) and platelet count decrease (10.8%). No treatment-related deaths occurred. Analysis of single immune subpopulations revealed a significant association of pCR with higher baseline infiltration by stromal (s)-CD20+, s-CD8+ and s-CD4+ TILs. Unsupervised hierarchical clustering of stromal immune markers identified a group of patients characterised by high s-CD20+, s-CD8+, s-CD4+ and s-FOXP3+ immune cells infiltration, which was independently associated with pCR. CONCLUSION: Neoadjuvant pyrotinib plus trastuzumab-based chemotherapy exhibits promising efficacy and manageable toxicity in patients with human epidermal growth factor receptor 2-positive early BC, and thus phase 3 trials are warranted. Our findings also contribute to understanding the potential role of the immune microenvironment in response to neoadjuvant pyrotinib-based therapy.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Acrilamidas , Aminoquinolinas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Carboplatina , Docetaxel/uso terapêutico , Feminino , Humanos , Linfócitos do Interstício Tumoral , Terapia Neoadjuvante/efeitos adversos , Receptor ErbB-2/metabolismo , Trastuzumab , Microambiente Tumoral
17.
Rev Prat ; 72(1): 43-49, 2022 Jan.
Artigo em Francês | MEDLINE | ID: mdl-35258253

RESUMO

Contribution of neoadjuvant chemotherapy. IN RECTAL CANCER In patients with locally advanced rectal cancer, preoperative radiotherapy and complete mesorectal excision have reduced the risk of locoregional recurrence. However, these treatments have not reduced the risk of metastatic recurrence and the benefit of adjuvant chemotherapy has never been formally demonstrated. The chemotherapy efficacy on the rectal tumor as well as the difficulties to administer adjuvant chemotherapy after proctectomy has led to the development of treatment regimens with neoadjuvant chemotherapy. Two phase III studies evaluating induction chemotherapy with FOLFIRINOX followed by chemoradiotherapy for one and short radiotherapy followed by consolidation chemotherapy for the other are positive for their main objective and constitute new therapeutic standards.


Apport de la chimiothérapie néoadjuvante dans le cancer du rectum. Chez les patients dont le cancer du rectum est locale¬ment avancé, la radiothérapie préopératoire et l'exérèse complète du mésorectum ont permis de réduire le risque de récidive locorégionale. Ces traitements n'ont en re¬vanche pas permis de réduire le risque de récidive métastatique, et le bénéfice d'une chimiothérapie adju¬vante n'a jamais été formellement démontré. L'efficaci¬té de la chimiothérapie sur la tumeur rectale, ainsi que les difficultés à administrer une chimiothérapie adjuvante après proctectomie, ont amené au développement de schémas thérapeutiques incluant une chimiothérapie néoadjuvante. Deux études de phase III ayant évalué une chimiothérapie d'induction par FOLFIRINOX suivie d'une chimioradiothérapie pour l'une et une radiothéra¬pie courte puis d'une chimiothérapie de consolidation pour l'autre sont positives pour leur objectif principal et constituent de nouveaux standards thérapeutiques.


Assuntos
Neoplasias Pancreáticas , Neoplasias Retais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Quimioterapia Adjuvante , Humanos , Terapia Neoadjuvante/efeitos adversos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/cirurgia
18.
Rev Prat ; 72(1): 50-54, 2022 Jan.
Artigo em Francês | MEDLINE | ID: mdl-35258254

RESUMO

Rectal cancer: is the era for de-escalation arrived? The reference treatment of rectal cancer relies on carcinologic resection including total mesorectal excision. In patients with locally advanced rectal cancer (cT3T4 and/or cN+), preoperative treatment is used to improve outcome and includes radiochemotherapy to optimize local control and systemic chemotherapy to decrease metastatic recurrence. The combination of these treatments with rectal cancer surgery induces short term and long-term toxicities potentially leading to treatment related sequelae on digestive and genitourinary function. Lastly, time is coming for de-escalation for the treatment to rectal cancer. For patients with small tumors (cT2T3 inférieur 4 cm) who respond to radiochemotherapy, organ preservation avoiding rectal resection can be discussed. In patients with locally advanced resectable rectal cancer, preoperative chemotherapy without pelvic irradiation could be used before total mesorectal excision to decrease the risk of long-term side effects. In patients with more advanced, primarily non resectable rectal cancer, a tailored strategy based on tumor response to chemotherapy could be used to rationalize the use of preoperative irradiation. New treatment strategies are constantly proposed and the optimal treatment option should be decided on a per patient basis during multidisciplinary discussion.


PERSPECTIVES: vers une désescalade thérapeutique dans le cancer du rectum ? Le traitement de référence des cancers du rectum repose sur l'exérèse carcinologique (exérèse totale du mésorectum). En cas de tumeur localement évoluée (cT3T4 et/ou N+), une radiochimiothérapie précédée ou suivie d'une chimiothérapie est utilisée en préopératoire pour améliorer le contrôle local et réduire le risque de récidive métastatique ; sa combinaison à une chirurgie lourde est associée à une toxicité à court et à long termes, avec un risque de séquelles fonctionnelles digestives et génito-urinaires. Actuellement, la prise en charge évolue vers une désescalade thérapeutique. En cas de tumeur T2T3 de petite taille (inférieure à 4 cm) répondant bien au traitement, une stratégie de préservation rectale évitant la chirurgie d'exérèse peut se discuter. Pour les tumeurs plus évoluées, une chirurgie d'exérèse précédée d'une chimiothérapie, sans irradiation pelvienne, pourrait limiter les séquelles à long terme. En cas de tumeur non résécable d'emblée, une démarche personnalisée, fondée sur l'intensité de la réponse tumorale à la chimiothérapie, permettrait un recours sélectif à l'irradiation pelvienne. Compte tenu des nombreuses nouvelles approches qui peuvent être proposées, une discussion pluridisciplinaire est absolument nécessaire pour optimiser la prise en charge des patients.


Assuntos
Protectomia , Neoplasias Retais , Quimiorradioterapia , Humanos , Terapia Neoadjuvante/efeitos adversos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/patologia , Reto/patologia , Reto/cirurgia
19.
J Sex Med ; 19(4): 613-619, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35227622

RESUMO

BACKGROUND: Cervical cancer survivors report the worst quality of life (QoL) among all cancer survivors and this is mainly due to their younger age and the long-term treatment sequelae. AIM: The purpose of this study is to assess the long-term QoL and sexual function of locally advanced cervical cancer (LACC) patients treated with neoadjuvant chemotherapy (NACT) and radical hysterectomy (RH) instead of the standard chemoradiotherapy. METHODS: This is a retrospective case-control study including LACC patients (FIGO stage IIB-IVA) treated with the NACT-RH strategy and a control group of healthy women undergoing hysterectomy for uterine fibromatosis in the same period. OUTCOMES: Main outcome measures were the EORTC QLQ-C30 and EORTC QLQ-CX24 for quality of life and Female Sexual Function Index (FSFI) for sexual function. RESULTS: Overall, 96 patients were included: 48 LACC and 48 controls. The mean age at diagnosis was 45.5 ± 9.0 and 47.0 ± 7.8, respectively (P = .38). Compared to controls, LACC patients reported lower mean scores for the global health status (69.4 ± 22.6 vs 81.2 ± 24.3; Mean Difference (MD): -11.80 [95% CI: -21.19, -2.41]; P = .016), QLQ-C30 functional scale (80.1 ± 22.6 vs 92.4 ± 14.9; MD: -12.30 [95% CI: -19.96, -4.64]; P = .002), QLQ-Cx24 functional scale (55.5 ± 25.0 vs 80.4 ± 22.4; MD: -24.00 [95% CI: -34.40, -15.40]; P < .001), and the total FSFI (19.3 ± 9.6 vs 26.2 ± 9.9; MD: -6.90 [95% CI: -10.80, -3.00]; P < .001). On the other hand, LACC patients reported higher mean scores on the QLQ-C30 (16.9 ± 22.1 vs 8.4 ± 16.6; MD: 8.50 [95% CI: 0.68, 16.32]; P = .03) and QLQ-CX24 (26.0 ± 28.8 vs 15.0 ± 11.7; MD: 11.00 [95% CI: -2.21, 19.79]; P = .01) symptoms scales. CLINICAL IMPLICATIONS: The confirmed poor quality of life even in surgically treated LACC survivors underlines the importance of tailoring parametrectomy based on lymph node status and developing personalized strategies. STRENGTHS AND LIMITATIONS: The study assessed the long-term QoL and sexual function in the specific subpopulation of LACC patients treated with NACT-RH. Main limitations include the small sample size and the retrospective design. CONCLUSION: LACC long-term survivors treated with NACT-RH experience poor QoL and sexual dysfunction. Palaia I, Santangelo G, Caruso G, et al. Long-term Quality of Life and Sexual Function After Neoadjuvant Chemotherapy and Radical Surgery for Locally Advanced Cervical Cancer. J Sex Med 2022;19:613-619.


Assuntos
Qualidade de Vida , Neoplasias do Colo do Útero , Estudos de Casos e Controles , Feminino , Humanos , Histerectomia , Terapia Neoadjuvante/efeitos adversos , Estudos Retrospectivos , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/cirurgia
20.
Oncology ; 100(5): 257-266, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35114682

RESUMO

BACKGROUND: De-escalation therapy omitting anthracycline has been generally adopted for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer in the adjuvant setting, but not in the neoadjuvant chemotherapy (NAC) setting. We investigated whether anthracycline can be omitted in HER2-positive early breast cancer patients receiving neoadjuvant taxane plus trastuzumab with clinical response. METHODS: HER2-positive primary breast cancer patients treated using NAC containing trastuzumab were enrolled between September 2006 and July 2018 at Osaka Breast Clinic. The primary outcome was disease-free survival (DFS). The secondary outcome was overall survival (OS). We investigated survival with or without fluorouracil, epirubicin, and cyclophosphamide (FEC) using the log-rank test and propensity score matching (PSM). RESULTS: In total, 142 patients were retrospectively included and median follow-up was 61 months. There was no significant difference in DFS (p = 0.93) and OS (p = 0.46) between the FEC-omitted group and the FEC-added group. The 5-year DFS was 91% and 88% and OS was 100% and 100%, respectively. After PSM, the FEC-omitted group and the FEC-added group had no significant differences in DFS (p = 0.459) and there were no death events in either group. The 5-year DFS was 90% and 88% and OS was 100% and 100%, respectively. CONCLUSIONS: Using PSM, the 5-year DFS of HER2-positive early breast cancer was not different with or without anthracycline. Response-guided omission of anthracycline may be an option for HER2-positive early breast cancer patients receiving neoadjuvant taxane and trastuzumab with good response in order to avoid overtreatment.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Antraciclinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Ciclofosfamida , Epirubicina , Feminino , Fluoruracila , Seguimentos , Humanos , Terapia Neoadjuvante/efeitos adversos , Prognóstico , Pontuação de Propensão , Receptor ErbB-2/metabolismo , Estudos Retrospectivos , Taxoides/uso terapêutico , Trastuzumab
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