Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 82
Filtrar
1.
Future Oncol ; 20(7): 393-407, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37850363

RESUMO

Cetuximab every 2 weeks (Q2W) dosing schedule is approved by the US FDA and by the Japanese Pharmaceuticals and Medical Devices Agency in patients with metastatic colorectal cancer and squamous cell carcinoma of the head and neck. Phase II trials have found comparable efficacy and safety for the weekly (Q1W) and Q2W schedules, and real-world studies have shown noninferiority of the Q2W compared with the Q1W schedule. Several guidelines recommend cetuximab Q2W administration as an alternative to the Q1W dosing schedule. Cetuximab Q2W can be administered with a Q2W dose of chemotherapy, making it a more convenient option to the Q1W schedule, potentially resulting in reduced costs for administration, increased flexibility for clinical staff and improved patient adherence.


Cetuximab is a drug for patients with colorectal cancer or cancer of the head and neck. It is usually administered once a week. However, studies have shown that cetuximab given once every 2 weeks instead has similar clinical benefits and side effects. Based on this evidence, the every 2 weeks dosing schedule has been approved for use in USA and Japan. The every 2 weeks dosing schedule is a convenient alternative to the weekly schedule. It may result in fewer hospital visits, improved patient quality of life, reduced healthcare costs and more flexibility for medical staff. This review summarizes the current evidence and benefits for the every 2 weeks dosing schedule.


Assuntos
Carcinoma de Células Escamosas , Humanos , Cetuximab/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica
2.
Curr Opin Oncol ; 35(3): 166-177, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36966495

RESUMO

PURPOSE OF REVIEW: Clinical data on salvage chemotherapy used after checkpoints inhibitors in oncology are reviewed, with a special focus on recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). RECENT FINDINGS: Converging evidence is emerging about high response and/or disease control rates associated with salvage chemotherapy after immunotherapy failure in advanced solid tumours. This phenomenon is mainly reported in retrospective studies for "hot tumours" such as R/M HNSCC, melanoma, lung, urothelial or gastric cancers, but also in haematological malignancies. Some physiopathological hypotheses have been raised. SUMMARY: Several independent series show increased response rates associated with postimmuno chemotherapy when compared with retrospective series in similar settings. Several mechanisms could be involved such as a "carry-over" allowed by a persistence of the checkpoint inhibitor, a modulation of tumour microenvironment components but also an intrinsic immunomodulatory effect of chemotherapy, increased by a specific immunologic state induced by the therapeutic pressure of checkpoint inhibitors. These data establish a rationale for prospectively evaluating the features of postimmunotherapy salvage chemotherapy.


Assuntos
Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Estudos Retrospectivos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Imunoterapia , Microambiente Tumoral
3.
Oncologist ; 27(2): e194-e198, 2022 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-35641218

RESUMO

In the randomized, phase 3 CheckMate 141 trial, nivolumab significantly improved overall survival (OS) versus investigator's choice (IC) of chemotherapy at primary analysis among 361 patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) post-platinum therapy. Nivolumab versus IC as first-line treatment also improved OS among patients with R/M SCCHN who progressed on platinum therapy for locally advanced disease in the adjuvant or primary setting at 1-year follow-up. In the present long-term follow-up analysis of patients receiving first-line treatment, OS benefit with nivolumab (n = 50) versus IC (n = 26) was maintained (median: 7.7 months versus 3.3 months; hazard ratio: 0.56; 95% confidence interval, 0.34-0.94) at 2 years. No new safety signals were identified. In summary, this long-term 2-year analysis of CheckMate 141 supports the use of nivolumab as a first-line treatment for patients with platinum-refractory R/M SCCHN.


Assuntos
Neoplasias de Cabeça e Pescoço , Nivolumabe , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Nivolumabe/uso terapêutico , Platina/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico
4.
Curr Opin Oncol ; 34(3): 196-203, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35671120

RESUMO

PURPOSE OF REVIEW: The treatment of recurrent and/or metastatic head and neck squamous cell carcinoma patients is revolutionized by the advent of anti-PD1 checkpoint inhibitors. RECENT FINDINGS: Indeed, Pembrolizumab is approved as monotherapy or used in combination with platin and fluorouracil for first-line patients with tumors expressing PD-L1. Nivolumab and Pembrolizumab are also approved in second line of recurrent/metastatic head and neck squamous cell carcinoma. Moreover, the substitution of fluorouracil for a taxane in the TPEx regimen has shown improvement in safety profile when compared with EXTREME regimen. SUMMARY: Here we carry out a review of the main results of pivotal trials and discuss the pros and cons of the three possible scenarios when considering the therapeutic sequence (first and second line).


Assuntos
Neoplasias de Cabeça e Pescoço , Recidiva Local de Neoplasia , Fluoruracila/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Nivolumabe/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico
5.
Lancet Oncol ; 22(4): 463-475, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33684370

RESUMO

BACKGROUND: Results from a phase 2 trial of the TPEx chemotherapy regimen (docetaxel-platinum-cetuximab) showed promising results, with a median overall survival of 14·0 months in first-line recurrent or metastatic head and neck squamous-cell carcinoma (HNSCC). We therefore aimed to compare the efficacy and safety of the TPEx regimen with the standard of care EXTREME regimen (platinum-fluorouracil-cetuximab) in this setting. METHODS: This was a multicentre, open-label, randomised, phase 2 trial, done in 68 centres (cancer centres, university and general hospitals, and private clinics) in France, Spain, and Germany. Eligible patients were aged 18-70 years with histologically confirmed recurrent or metastatic HNSCC unsuitable for curative treatment; had at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1; and had an Eastern Cooperative Oncology Group (ECOG) performance status of 1 or less. Participants were randomly assigned (1:1) using the TenAlea website by investigators or delegated clinical research associates to the TPEx regimen or the EXTREME regimen, with minimisation by ECOG performance status, type of disease evolution, previous cetuximab treatment, and country. The TPEx regimen consisted of docetaxel 75 mg/m2 and cisplatin 75 mg/m2, both intravenously on day 1, and cetuximab on days 1, 8, and 15 (intravenously 400 mg/m2 on day 1 of cycle 1 and 250 mg/m2 weekly subsequently). Four cycles were repeated every 21 days with systematic granulocyte colony-stimulating factor (G-CSF) support at each cycle. In case of disease control after four cycles, intravenous cetuximab 500 mg/m2 was continued every 2 weeks as maintenance therapy until progression or unacceptable toxicity. The EXTREME regimen consisted of fluorouracil 4000 mg/m2 on day 1-4, cisplatin 100 mg/m2 on day 1, and cetuximab on days 1, 8, and 15 (400 mg/m2 on day 1 of cycle 1 and 250 mg/m2 weekly subsequently) all delivered intravenously. Six cycles were delivered every 21 days followed by weekly 250 mg/m2 cetuximab as maintenance therapy in case of disease control. G-CSF support was not mandatory per the protocol in the EXTREME regimen. The primary endpoint was overall survival in the intention-to-treat population; safety was analysed in all patients who received at least one dose of chemotherapy or cetuximab. Enrolment is closed and this is the final analysis. This study is registered at ClinicalTrials.gov, NCT02268695. FINDINGS: Between Oct 10, 2014, and Nov 29, 2017, 541 patients were enrolled and randomly assigned to the two treatment regimens (271 to TPEx, 270 to EXTREME). Two patients in the TPEx group had major deviations in consent forms and were not included in the final analysis. Median follow-up was 34·4 months (IQR 26·6-44·8) in the TPEx group and 30·2 months (25·5-45·3) in the EXTREME group. At data cutoff, 209 patients had died in the TPEx group and 218 had died in the EXTREME group. Overall survival did not differ significantly between the groups (median 14·5 months [95% CI 12·5-15·7] in the TPEx group and 13·4 months [12·2-15·4] in the EXTREME group; hazard ratio 0·89 [95% CI 0·74-1·08]; p=0·23). 214 (81%) of 263 patients in the TPEx group versus 246 (93%) of 265 patients in the EXTREME group had grade 3 or worse adverse events during chemotherapy (p<0·0001). In the TPEx group, 118 (45%) of 263 patients had at least one serious adverse event versus 143 (54%) of 265 patients in the EXTREME group. 16 patients in the TPEx group and 21 in the EXTREME group died in association with adverse events, including seven patients in each group who had fatal infections (including febrile neutropenia). Eight deaths in the TPEx group and 11 deaths in the EXTREME group were assessed as treatment related, most frequently sepsis or septic shock (four in each treatment group). INTERPRETATION: Although the trial did not meet its primary endpoint, with no significant improvement in overall survival with TPEx versus EXTREME, the TPEx regimen had a favourable safety profile. The TPEx regimen could provide an alternative to standard of care with the EXTREME regimen in the first-line treatment of patients with recurrent or metastatic HNSCC, especially for those who might not be good candidates for up-front pembrolizumab treatment. FUNDING: Merck Santé and Chugai Pharma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cetuximab/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Docetaxel/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , França/epidemiologia , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Platina/administração & dosagem , Espanha/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
6.
Curr Opin Oncol ; 33(3): 160-167, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33782359

RESUMO

PURPOSE OF REVIEW: Worldwide, head and neck carcinomas account for 5% of all malignancies. Two-thirds of patients relapse after initial multimodal therapy. Until early 2010, the median overall survival (OS) of metastatic patients was about 10 months. RECENT FINDINGS: New drugs have been incorporated in patient management, thus enabling an increase in OS. Several first and second line protocols are now available but the lack of direct comparison makes the choice difficult between them. SUMMARY: This work aims to define the comprehensive medical management of patients with relapsing head and neck carcinoma. In September 2020, the French head and neck groups GORTEC, Unicancer head and Neck group, GROCC and GETTEC decided to promote a one-day meeting to propose how to incorporate these new regimens in first and second line treatment for recurrent and metastatic head and neck cancer (R/M SCCHNC). Twelve French medical oncologist involved in the management of R/M SCCHNC for more than 10 years examined the literature and proposed a simple and practical management based on five criteria: age, delay from last platinum injection, combined positive score expression level, FIT or UNFIT patient according to physician decision, fast response needed or not.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Fatores Etários , Idoso , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Metástase Neoplásica , Ensaios Clínicos Controlados Aleatórios como Assunto , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
7.
Invest New Drugs ; 39(6): 1641-1648, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34322775

RESUMO

Background The phosphatidylinositol-3 kinase pathway is often altered in head and neck squamous cell carcinoma (HNSCC), and is involved in the resistance to EGFR inhibitors. Objective We investigated the dose-limiting toxicities (DLTs), maximum tolerated dose, pharmacokinetics, and preliminary efficacy of the combination of copanlisib, an intravenous, pan-class I PI3K inhibitor, with the anti-EGFR monoclonal antibody cetuximab in recurrent and/or metastatic HNSCC patients in a phase I dose-escalation trial. Patients and methods Copanlisib was given intravenously on days 1, 8, and 15 of 28-day cycles at the dose of 45 mg and 30 mg, in combination with standard doses of weekly cetuximab (400 mg/m2 loading dose followed by 250 mg/m2 on days 8, 15, and 22, and weekly thereafter). Results Three patients received copanlisib 45 mg, of whom two experienced grade 3 hyperglycemia during Cycle 1 that met the DLT criteria. Eight patients were then treated with copanlisib at the dose of 30 mg. Because of the occurrence of hyperglycemia, a premedication with metformine was introduced on the day of the injections. No DLTs were reported at this dose level. The trial was stopped early because of the unfavourable toxicity profile of the combination. Among eight evaluable patients for response, four patients (50%) had disease stabilization according to RECIST1.1 as best response. Conclusion Copanlisib combined with cetuximab demonstrated unfavorable toxicity and limited efficacy in heavily pretreated recurrent and/or metastatic HNSCC patients.Trial registration NCT02822482, Date of registration: June 2016.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Inibidores de Fosfoinositídeo-3 Quinase/uso terapêutico , Pirimidinas/uso terapêutico , Quinazolinas/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Área Sob a Curva , Cetuximab/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Meia-Vida , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Inibidores de Fosfoinositídeo-3 Quinase/administração & dosagem , Inibidores de Fosfoinositídeo-3 Quinase/efeitos adversos , Inibidores de Fosfoinositídeo-3 Quinase/farmacocinética , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Pirimidinas/farmacocinética , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Quinazolinas/farmacocinética
8.
Cancer ; 125(18): 3208-3218, 2019 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-31246283

RESUMO

BACKGROUND: Response patterns with immune checkpoint inhibitors may be different from those with chemotherapy. Therefore, assessment of response to immunotherapy with the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, could result in premature treatment termination. The randomized, open-label, phase 3 CheckMate 141 trial (NCT02105636), which evaluated nivolumab in recurrent/metastatic squamous cell carcinoma of the head and neck after platinum therapy, allowed treatment beyond first RECIST-defined progression (TBP) according to protocol-specified criteria. METHODS: In CheckMate 141, patients with RECIST-defined progression who had a stable performance status and demonstrated clinical benefit without rapid disease progression were permitted to receive TBP with nivolumab at 3 mg/kg every 2 weeks until further progression, which was defined as an additional ≥10% increase in tumor volume. This post hoc analysis evaluated outcomes for patients who received TBP with nivolumab. RESULTS: Of 240 patients randomized to nivolumab, 146 experienced RECIST-defined progression. Sixty-two of these patients received TBP, and 84 discontinued treatment (no TBP). Among the 60 TBP patients evaluable for response, 15 (25%) had no change in their tumor burden, and 15 (25%) had reductions in target lesion size; 3 patients (5%) had reductions >30%. The median overall survival among TBP patients was 12.7 months (95% confidence interval, 9.7-14.6 months). No new safety signals were observed with TBP. Exploratory analyses of immune cell biomarkers suggested a potential relationship with initial and TBP responses. CONCLUSIONS: Tumor burden reduction was noted in a proportion of patients who received TBP with nivolumab in CheckMate 141. Additional research is warranted to identify factors predictive of a TBP benefit in this population.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Nivolumabe/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Pulmonares/secundário , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço/secundário , Resultado do Tratamento
9.
N Engl J Med ; 375(19): 1856-1867, 2016 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-27718784

RESUMO

BACKGROUND: Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after platinum chemotherapy have a very poor prognosis and limited therapeutic options. Nivolumab, an anti-programmed death 1 (PD-1) monoclonal antibody, was assessed as treatment for this condition. METHODS: In this randomized, open-label, phase 3 trial, we assigned, in a 2:1 ratio, 361 patients with recurrent squamous-cell carcinoma of the head and neck whose disease had progressed within 6 months after platinum-based chemotherapy to receive nivolumab (at a dose of 3 mg per kilogram of body weight) every 2 weeks or standard, single-agent systemic therapy (methotrexate, docetaxel, or cetuximab). The primary end point was overall survival. Additional end points included progression-free survival, rate of objective response, safety, and patient-reported quality of life. RESULTS: The median overall survival was 7.5 months (95% confidence interval [CI], 5.5 to 9.1) in the nivolumab group versus 5.1 months (95% CI, 4.0 to 6.0) in the group that received standard therapy. Overall survival was significantly longer with nivolumab than with standard therapy (hazard ratio for death, 0.70; 97.73% CI, 0.51 to 0.96; P=0.01), and the estimates of the 1-year survival rate were approximately 19 percentage points higher with nivolumab than with standard therapy (36.0% vs. 16.6%). The median progression-free survival was 2.0 months (95% CI, 1.9 to 2.1) with nivolumab versus 2.3 months (95% CI, 1.9 to 3.1) with standard therapy (hazard ratio for disease progression or death, 0.89; 95% CI, 0.70 to 1.13; P=0.32). The rate of progression-free survival at 6 months was 19.7% with nivolumab versus 9.9% with standard therapy. The response rate was 13.3% in the nivolumab group versus 5.8% in the standard-therapy group. Treatment-related adverse events of grade 3 or 4 occurred in 13.1% of the patients in the nivolumab group versus 35.1% of those in the standard-therapy group. Physical, role, and social functioning was stable in the nivolumab group, whereas it was meaningfully worse in the standard-therapy group. CONCLUSIONS: Among patients with platinum-refractory, recurrent squamous-cell carcinoma of the head and neck, treatment with nivolumab resulted in longer overall survival than treatment with standard, single-agent therapy. (Funded by Bristol-Myers Squibb; CheckMate 141 ClinicalTrials.gov number, NCT02105636 .).


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/efeitos adversos , Antígeno B7-H1/metabolismo , Carcinoma de Células Escamosas/metabolismo , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Masculino , Nivolumabe , Qualidade de Vida , Análise de Sobrevida
10.
Curr Opin Oncol ; 31(3): 146-151, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30893146

RESUMO

PURPOSE OF REVIEW: Checkpoint inhibitors (CPI) are revolutionizing the treatment of advanced cancers including recurrent and or metastatic squamous cell carcinoma of the head and neck (RM-SCCHN). RECENT FINDINGS: In this review, we will summarize the results of prospective trials evaluating CPI and particularly antiprogrammed death 1 (PD-1)/antiprogrammed death-ligand 1 (PD-L1) in RM-SCCHN. SUMMARY: Nivolumab and Pembrolizumab, two anti-PD-1 CPI, were associated with longer overall survival than standard chemotherapy in pretreated RM-SCCHN in two randomized phase 3 trials (respectively CHECKMATE-141 and KEYNOTE-040). Both are now approved in this setting. In the KEYNOTE-048 trial, the pembrolizumab was also associated with a longer survival when compared with the EXTREME regimen in first-line RM-SCCHN patients whose tumors overexpressed PD-L1 (combined positive score ≥20%). This trial also showed a superiority of platinum-based chemotherapy and pembrolizumab vs. EXTREME regimen in unselected first-line RM-SCCHN. Pembrolizumab will probably be the next standard of care for first-line RM-SCCHN with high expression of PD-L1. Further evaluation of CPI combined with other antitumoral agents is ongoing in advanced and locally advanced SCCHN.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Nivolumabe/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Metástase Neoplásica , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Nivolumabe/administração & dosagem , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
11.
Curr Opin Oncol ; 31(3): 131-137, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30893149

RESUMO

PURPOSE OF REVIEW: The aim of this review is to summarize the current knowledge on the genomic characterization of squamous cell carcinomas of the head and neck (HNSCC) and discusses how these abnormalities could be incorporated into a therapeutic approach. RECENT FINDINGS: Tobacco and HPV infection, the two main risk factors of HNSCC, allow the definition of two groups with distinct anatomoclinical and genetic features. As tobacco and HPV infection are not exclusive, exposure to both risk factors is associated with an intermediate prognostic. HPV-positive, nontobacco-related HNSCCs are associated with a better prognosis, a rather more simple genomic profile, frequent activating mutations of genes involved in pi3kinase pathway, and the very low incidence of mutations of tumor suppressor genes. HPV-negative, tobacco-related HNSCC are genetically more complex. HPV-negative HNSCC are characterized by almost mandatory inactivating mutations/deletions of tumor suppressor genes (especially TP53 and CDKN2A) and the occurrence, though less frequent, of activating mutations or amplifications of some oncogenes that encode for cell cycle proteins or receptors with tyrosine kinase activity. Despite many efforts to improve therapeutic targeting in RM HNSCC, Cetuximab, a monoclonal antibody targeting REGF, remains the sole approved targeted treatment in RM HNSCC. SUMMARY: Despite the increasingly precise genomic characterization of HNSCCs, precision medicine is struggling to find its place in the management of HNSCCs. Inclusion of enriched populations in dedicated trials is likely to help implement precision medicine in the management of HNSCCs.


Assuntos
Neoplasias de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Genômica , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/virologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Terapia de Alvo Molecular , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia
12.
Curr Opin Oncol ; 31(3): 152-159, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30985496

RESUMO

PURPOSE OF REVIEW: Elderly head and neck cancer (HNC) patients are very rarely enrolled in clinical trials, and even more so in dedicated trials in curative or palliative setting. As a result, no standards of treatment exist for this population and thus, adaptation of standard treatments is commonly used. RECENT FINDINGS: The choice between a monotherapy and a platinum-cetuximab combination is based on the performance status, which is not suitable and/or sufficient to evaluate the patient ability to receive a systemic treatment combined or not with radiotherapy. The evaluation of functional age using geriatric assessment is recommended. However, access to comprehensive geriatric assessment is limited in many centers, and the choice of the type of treatment is often not based on objective and reproducible criteria. As a result, fragile elderly HNC patients may be overtreated with a risk of increased toxicity and fit patients proposed for suboptimal treatment with a risk of failure of tumor control. SUMMARY: It is therefore crucial to develop and evaluate customized treatments by enrolling elderly HNC patients in dedicated therapeutics trials, such as the ELAN (Elderly Head and Neck Cancer) studies or new approaches involving promising immunotherapies. To administer the most suitable therapy, a simple and reproducible geriatric assessment could efficiently guide practitioners.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Cetuximab/administração & dosagem , Ensaios Clínicos Fase III como Assunto , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Compostos Organoplatínicos/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia
13.
Clin Chem ; 65(10): 1267-1275, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31387885

RESUMO

BACKGROUND: This prospective multicenter study evaluated the prognostic value of circulating tumor cells (CTCs) in relapsing nonoperable or metastatic head and neck squamous cell carcinoma (rHNSCC) treated by chemotherapy and cetuximab. METHODS: In 65 patients suitable for analyses, peripheral blood was taken at day 0 (D0) D7, and D21 of treatment for CTC detection by CellSearch®, EPISPOT, and flow cytometry (FCM). Progression-free survival (PFS) was assessed with the Kaplan-Meier method and compared with the log-rank test (P < 0.05). RESULTS: At D0, CTCs were detected with EPISPOT, CellSearch, and FCM in 69% (45/65), 21% (12/58), and 11% (7/61) of patients, respectively. In the patients tested with all 3 methods, EPISPOT identified 92% (36/39), 92% (35/38), and 90% (25/28) of all positive samples at D0, D7, and D21, respectively. Median PFS time was significantly lower in (a) patients with increasing or stable CTC counts (36/54) from D0 to D7 with EPISPOTEGFR (3.9 vs 6.2 months; 95% CI, 5.0-6.9; P = 0.0103) and (b) patients with ≥1 CTC detected with EPISPOT or CellSearch® (37/51) (P = 0.0311), EPISPOT or FCM (38/54) (P = 0.0480), and CellSearch or FCM (11/51) (P = 0.0005) at D7. CONCLUSIONS: CTCs can be detected before and during chemotherapy in patients with rHNSCC. D0-D7 CTC kinetics evaluated with EPISPOTEGFR are associated with the response to treatment. This study indicates that CTCs can be used as a real-time liquid biopsy to monitor the early response to chemotherapy in rHNSCC. CLINICALTRIALSGOV IDENTIFIER: NCT02119559.


Assuntos
Neoplasias de Cabeça e Pescoço/sangue , Células Neoplásicas Circulantes/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Contagem de Células , Intervalo Livre de Doença , Citometria de Fluxo , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Prospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/secundário
14.
Br J Clin Pharmacol ; 85(6): 1357-1366, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30811063

RESUMO

AIMS: Cetuximab associated with cisplatin and 5-fluorouracil is used to treat patients with inoperable or metastatic head and neck squamous cell carcinomas (HNSCC) up until disease progression or unacceptable toxicities. To date, no biomarkers of efficacy are available to select patients who will benefit from treatment. METHODS: An ancillary pharmacokinetics (PK) exploration was performed in the context of a prospective study investigating circulating-tumour cells vs progression-free survival (PFS). Cetuximab plasma concentrations were analysed according to a population PK model. Individual exposure parameters were confronted with soluble epidermal growth factor receptor (sEGFR) concentrations, tumour response and PFS. RESULTS: PK data (28 patients, 203 observations) were best described by a two-compartment model with linear elimination. Performance status (PS) significantly correlated to both cetuximab clearance and central volume of distribution with both parameters increasing by 33.3% (95% CI 1-65.6) for each 1-point increase of PS compared to PS = 0. Univariate analysis showed that patients with higher trough cetuximab concentrations at Day 7 (Cmin,D7 ) had better tumour response (P = 0.03) and longer PFS (P = 0.035). However, multivariate analysis revealed that only PS and tumour size at baseline remained significantly associated with PFS. Levels of sEGFR increased during cetuximab treatment but were not associated with PFS in the multivariate analysis. CONCLUSIONS: Our study prospectively indicates that PS is likely a confounding factor in the relationship between cetuximab PK and PFS, patients with a poor PS having lower cetuximab plasma exposure and lower PFS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Cetuximab/farmacocinética , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Modelos Biológicos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais/sangue , Cetuximab/administração & dosagem , Cetuximab/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/farmacocinética , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/sangue , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/farmacocinética , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Células Neoplásicas Circulantes/efeitos dos fármacos , Células Neoplásicas Circulantes/patologia , Intervalo Livre de Progressão , Estudos Prospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Adulto Jovem
15.
Curr Treat Options Oncol ; 20(8): 65, 2019 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-31240480

RESUMO

OPINION STATEMENT: For most of patients with a recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC), the treatment remains palliative: The main objective is to reduce the symptoms related to the locoregional relapse, prolong life while maintaining quality of life, which is a big challenge. The systemic treatment needs to be adapted to the performance status, comorbidities, and sequelae of patients. For fit patients, the combination of platinum-based chemotherapy and cetuximab (EXTREME) is the standard of care in first-line treatment since 2008, as no other targeted therapy has been approved in this setting until now. The replacement of 5-FU with a taxane (docetaxel) in the EXTREME regimen has been explored in the large randomized international study TPExtreme which results are awaited in a few months. Depending on the study results on survival, response rate, and tolerance, the TPEx regimen may become a treatment option for patients with R/M HNSCC. Unfit patients are usually treated with platinum-free combinations or with the monotherapies which are recommended in second-line setting (methotrexate, taxanes, cetuximab). However, the irruption of new immunotherapies (e.g., checkpoint inhibitors (CPI)) is changing the guidelines. The tolerance of anti-PD-1 CPI is better than that of chemotherapy, and they seem to be a good option for unfit patients. Anti-PD-1 nivolumab and pembrolizumab are now approved for platinum refractory patients, providing prolonged survival in the case of response, and improvement in quality of life. New options arise in first-line setting with pembrolizumab alone or combined with chemotherapy. Patients with a high PD-L1 biomarker level seem to benefit more from immunotherapy. Other situations (e.g., PD-L1-low, PD-L1-negative, high tumor burden) may more likely to benefit from other combinations, such as cetuximab plus chemotherapy, to avoid local failures and life-threatening fast progression. In terms of perspectives, chemo-free and CPI-free approaches, using other immune oncology agents, should be the next steps.


Assuntos
Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Ensaios Clínicos como Assunto , Terapia Combinada , Gerenciamento Clínico , Neoplasias de Cabeça e Pescoço/etiologia , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Metástase Neoplásica , Estadiamento de Neoplasias , Recidiva , Resultado do Tratamento
16.
Eur Arch Otorhinolaryngol ; 276(9): 2531-2539, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31240456

RESUMO

BACKGROUND: Providing cancer patients with adequate information is essential to their confidence and satisfaction regarding medical care. The aims of this study were to evaluate the information given to patients undergoing total pharyngolaryngectomy (TPL) as well as the evolution and predictors of patient quality of life (QoL). METHODS: We conducted a prospective multicentric study on patients undergoing TPL for a locally advanced laryngeal/hypopharyngeal cancer. All patients completed the EORTC QLQ-INFO25, QLQ-C30, and QLQ-H&N35 questionnaires, before and after surgery. RESULTS: This study enrolled 46 patients. Between the pre- and post-therapeutic periods, we observed no significant changes in the global QLQ-INFO25 and QLQ-C30 scores. However, we found a significant deterioration in 4 QLQ-INFO25 scales/items and in social functioning, as well as an increase of sense, speech, and social contact problems. N-stage and professional activity were significant predictors of preoperative QLQ-INFO25 scores. Younger age was significantly associated with financial difficulties, whereas professional activity and lower education level were significant predictors of xerostomia and swallowing problems, respectively. CONCLUSION: In patients undergoing TPL, we observed significant changes in QLQ-INFO25 scores between the pre- and post-treatment periods and, particularly, a deterioration of patient satisfaction with the information received. Several clinical factors were identified as significant predictors of QLQ-INFO25 and QoL scores.


Assuntos
Neoplasias Hipofaríngeas , Neoplasias Laríngeas , Laringectomia/educação , Educação de Pacientes como Assunto , Faringectomia/educação , Complicações Pós-Operatórias/psicologia , Qualidade de Vida , Idoso , Feminino , Humanos , Neoplasias Hipofaríngeas/psicologia , Neoplasias Hipofaríngeas/cirurgia , Neoplasias Laríngeas/psicologia , Neoplasias Laríngeas/cirurgia , Laringectomia/métodos , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto/métodos , Educação de Pacientes como Assunto/estatística & dados numéricos , Satisfação do Paciente , Faringectomia/métodos , Estudos Prospectivos , Inquéritos e Questionários
17.
Oncologist ; 23(9): 1079-1082, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29866947

RESUMO

Nivolumab significantly improved overall survival (OS) vs investigator's choice (IC) of chemotherapy at the primary analysis of randomized, open-label, phase 3 CheckMate 141 in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN). Here, we report that OS benefit with nivolumab was maintained at a minimum follow-up of 11.4 months. Further, OS benefit with nivolumab vs IC was also noted among patients who received first-line treatment for R/M SCCHN after progressing on platinum therapy for locally advanced disease in the adjuvant or primary (i.e., with radiation) setting.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Nivolumabe/uso terapêutico , Antineoplásicos Imunológicos/farmacologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Recidiva Local de Neoplasia , Nivolumabe/farmacologia , Fatores de Tempo
18.
Neuroendocrinology ; 106(3): 264-273, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28813709

RESUMO

BACKGROUND: The natural history and the best modality of follow-up of atypical lung carcinoids (AC) remain ill defined. The aim of this study was to analyze recurrence-free survival (RFS) after complete resection (R0) of stage I-III pulmonary AC. Secondary objectives were prognostic parameters, the location of recurrences, and the modality of follow-up. METHODS: A retrospective review of 540 charts of AC patients treated between 1998 and 2008 at 10 French and Italian centers with experience in lung neuroendocrine tumor management was undertaken. The exclusion criteria were MEN1-related tumor, history of another cancer, referral after tumor relapse, and being lost to follow-up. A central pathological review was performed in each country. RESULTS: Sixty-two patients were included. After a median follow-up time of 91 months (mean 85, range 6-165), 35% of the patients experienced recurrence: 16% were regional recurrences and 19% were distant metastases. Median RFS was not reached. The 1-, 3-, and 5-year RFS rate was 90, 79, and 68%, respectively. In univariate analysis, lymph node involvement (p = 0.0001), stage (p = 0.0001), mitotic count (p = 0.004), and type of surgery (p = 0.043) were significantly associated with RFS. In multivariate analysis, lymph node involvement was significantly associated with RFS (HR 95% CI: 0.000-0.151; p = 0.004). During follow-up, somatostatin receptor scintigraphy, fibroscopy, and abdominal examination results were available for 22, 12, and 25 patients, respectively. The median time interval for imaging follow-up was 10 months. CONCLUSIONS: After complete resection of AC, recurrences were observed mostly within the first 5 years of follow-up, within bronchi, mediastinal nodes, the liver, and bones. In R0 patients, lymph node involvement could help to stratify follow-up intervals. Suboptimal imaging is evidenced.


Assuntos
Tumor Carcinoide/cirurgia , Neoplasias Pulmonares/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/epidemiologia , Tumor Carcinoide/patologia , Progressão da Doença , Intervalo Livre de Doença , Feminino , Seguimentos , França , Humanos , Itália , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos , Adulto Jovem
19.
Lancet Oncol ; 18(8): 1104-1115, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28651929

RESUMO

BACKGROUND: Patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck have few treatment options and poor prognosis. Nivolumab significantly improved survival of this patient population when compared with standard single-agent therapy of investigator's choice in Checkmate 141; here we report the effect of nivolumab on patient-reported outcomes (PROs). METHODS: CheckMate 141 was a randomised, open-label, phase 3 trial in patients with recurrent or metastatic squamous cell carcinoma of the head and neck who progressed within 6 months after platinum-based chemotherapy. Patients were randomly assigned (2:1) to nivolumab 3 mg/kg every 2 weeks (n=240) or investigator's choice (n=121) of methotrexate (40-60 mg/m2 of body surface area), docetaxel (30-40 mg/m2), or cetuximab (250 mg/m2 after a loading dose of 400 mg/m2) until disease progression, intolerable toxicity, or withdrawal of consent. On Jan 26, 2016, the independent data monitoring committee reviewed the data at the planned interim analysis and declared overall survival superiority for nivolumab over investigator's choice therapy (primary endpoint; described previously). The protocol was amended to allow patients in the investigator's choice group to cross over to nivolumab. All patients not on active therapy are being followed for survival. As an exploratory endpoint, PROs were assessed at baseline, week 9, and every 6 weeks thereafter using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30), the EORTC head and neck cancer-specific module (EORTC QLQ-H&N35), and the three-level European Quality of Life-5 Dimensions (EQ-5D) questionnaire. Differences within and between treatment groups in PROs were analysed by ANCOVA among patients with baseline and at least one other assessment. All randomised patients were included in the time to clinically meaningful deterioration analyses. Median time to clinically meaningful deterioration was analysed by Kaplan-Meier methods. CheckMate 141 was registered with ClinicalTrials.org, number NCT02105636. FINDINGS: Patients were enrolled between May 29, 2014, and July 31, 2015, and subsequently 361 patients were randomly assigned to receive nivolumab (n=240) or investigator's choice (n=121). Among them, 129 patients (93 in the nivolumab group and 36 in the investigator's choice group) completed any of the PRO questionnaires at baseline and at least one other assessment. Treatment with nivolumab resulted in adjusted mean changes from baseline to week 15 ranging from -2·1 to 5·4 across functional and symptom domains measured by the EORTC QLQ-C30, with no domains indicating clinically meaningful deterioration. By contrast, eight (53%) of the 15 domains in the investigator's choice group showed clinically meaningful deterioration (10 points or more) at week 15 (change from baseline range, -24·5 to 2·4). Similarly, on the EORTC QLQ-H&N35, clinically meaningful worsening at week 15 was seen in no domains in the nivolumab group and eight (44%) of 18 domains in the investigator's choice group. Patients in the nivolumab group had a clinically meaningful improvement (according to a difference of 7 points or greater) in adjusted mean change from baseline to week 15 on the EQ-5D visual analogue scale, in contrast to a clinically meaningful deterioration in the investigator's choice group (7·3 vs -7·8). Differences between groups were significant and clinically meaningful at weeks 9 and 15 in favour of nivolumab for role functioning, social functioning, fatigue, dyspnoea, and appetite loss on the EORTC QLQ-C30 and pain and sensory problems on the EORTC QLQ-H&N35. Median time to deterioration was significantly longer with nivolumab versus investigator's choice for 13 (37%) of 35 domains assessed across the three questionnaires. INTERPRETATION: In this exploratory analysis of CheckMate 141, nivolumab stabilised symptoms and functioning from baseline to weeks 9 and 15, whereas investigator's choice led to clinically meaningful deterioration. Nivolumab delayed time to deterioration of patient-reported quality-of-life outcomes compared with single-agent therapy of investigator's choice in patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck. In view of the major unmet need in this population and the importance of maintaining or improving quality of life for patients with recurrent or metastatic squamous cell carcinoma of the head and neck, these data support nivolumab as a new standard-of-care option in this setting. FUNDING: Bristol-Myers Squibb.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Qualidade de Vida , Anorexia/etiologia , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/secundário , Cetuximab/uso terapêutico , Progressão da Doença , Docetaxel , Dispneia/etiologia , Fadiga/etiologia , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Estimativa de Kaplan-Meier , Metotrexato/uso terapêutico , Recidiva Local de Neoplasia/complicações , Nivolumabe , Dor/etiologia , Medidas de Resultados Relatados pelo Paciente , Transtornos de Sensação/etiologia , Participação Social , Taxoides/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA