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1.
Eur Arch Otorhinolaryngol ; 270(1): 197-203, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23010793

RESUMO

Postoperative RT is generally recommended for laryngeal carcinomas (LSCCs) at high risk of recurrence after surgery. There are currently no clinicopathological parameters available to predict response to such adjuvant RT in LSCC, and only a few potentially predictive biomarkers have been investigated. Nm23-H1 protein is reportedly related to the tumor cells' metastatic potential, and low Nm23-H1 expression levels in human carcinomas often correlate with a poor prognosis. The novel aim of the present preliminary study was to investigate the prognostic value of Nm23-H1 expression and subcellular localization in a series of patients given postoperative RT for LSCC. A retrospective clinicopathological investigation was conducted at an academic tertiary referral center of 28 consecutive patients given postoperative RT for LSCC. Image analysis of immunohistochemical reactions was performed to measure Nm23-H1 total and nuclear expression levels. Disease-free survival (DFS) was significantly shorter among LSCC patients with total Nm23-H1 levels <50.0 % (p = 0.03); the mean total Nm23-H1 expression was lower in patients with recurrent disease than in patients without it (statistical trend, p = 0.07). The disease recurrence rate was significantly higher (p = 0.021) and the DFS shorter (statistical trend, p = 0.052) among LSCC patients with nuclear Nm23-H1 levels <5.0 %. The locoregional recurrence-risk ratio in LSCC patients with nuclear Nm23-H1 levels <5.0 % was 9.16. Nm23-H1 warrants further investigation of its potential role as a predictive biomarker with a view to providing tailored treatments after surgery, such as combinations of chemotherapy and RT instead of RT alone, in patients whose LSCCs have low or no Nm23-H1 expression.


Assuntos
Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/radioterapia , Nucleosídeo NM23 Difosfato Quinases/metabolismo , Biomarcadores Tumorais/metabolismo , Terapia Combinada , Diagnóstico por Imagem , Intervalo Livre de Doença , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Técnicas Imunoenzimáticas , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/cirurgia , Masculino , Gradação de Tumores , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Curva ROC , Estudos Retrospectivos , Estatísticas não Paramétricas
2.
J Oral Pathol Med ; 41(2): 136-40, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21943204

RESUMO

BACKGROUND: There are currently no clinical or pathological parameters able to predict response to adjuvant radiotherapy (RT) in laryngeal squamous cell carcinoma (LSCC). Few studies have investigated the molecular pathways potentially capable of predicting said response. The mammalian target of rapamycin (mTOR) acts as a 'master switch' protein in cancer cells, modulating metabolism, the cell cycle, and apoptosis. Cancer treatment with mTOR inhibitors (rapamycin analogs, or rapalogs) has produced promising results in various malignancies (renal cell carcinoma, breast cancer, prostate cancer, leukemia, lymphoma, and melanoma). The novel aim of the present study was to ascertain the prognostic role of mTOR expression in a series of patients with LSCC treated with primary surgery followed by RT. METHODS: The retrospective study involved 25 consecutive patients with LSCC given postoperative RT. Immunohistochemical mTOR expression was evaluated in primary LSCC by image analysis. RESULTS: The locoregional recurrence rate was significantly higher in patients with LSCC whose mTOR expression was >2.5% (P = 0.013). After postoperative RT, the locoregional recurrence risk ratio was 3.25 in LSCCs with mTOR >2.5%. The different disease-free survival was significantly shorter in cases of LSCC with mTOR >2.5% (P = 0.029). CONCLUSIONS: mTOR should be studied as a potential predictor for identifying LSCCs at higher risk of early recurrence after postoperative RT. New therapeutic strategies should be investigated in LSCC, including the use of rapalogs associated with conventional chemotherapeutic regimens in combination with RT.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias Laríngeas/radioterapia , Laringectomia , Serina-Treonina Quinases TOR/análise , Idoso , Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/cirurgia , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador , Neoplasias Laríngeas/cirurgia , Excisão de Linfonodo , Metástase Linfática/patologia , Masculino , Terapia Neoadjuvante , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Projetos Piloto , Prognóstico , Radioterapia Adjuvante , Radioterapia de Alta Energia , Estudos Retrospectivos , Resultado do Tratamento
3.
Cancers (Basel) ; 14(24)2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36551677

RESUMO

BACKGROUND: In patients affected by head and neck squamous cell carcinoma, the onset of severe oral mucositis is a decisive factor in completing concurrent chemo-radiotherapy, and few interventions have demonstrated a modest benefit. The primary aim of this clinical study was to evaluate the role of SAMITAL in reducing the incidence of severe mucositis induced by concurrent chemo-radiotherapy; the secondary aims were the tolerability and patient-reported quality of life measures. METHODS: Patients were randomized to receive SAMITAL granules for oral suspension of 20 mL, four-time daily or matching placebo in a 1:1 fashion using a stratified-block randomization scheme by disease site and type of chemotherapy. The SAMITAL/placebo was dispensed at the baseline visit and at each weekly visit following radiotherapy initiation. Patients were subjected to weekly endoscopic evaluations to assess the presence of mucositis. In addition, patient-reported outcomes were measured. RESULTS: Among the 116 patients treated with a median total dose of 66 Gy, 59 were randomized to SAMITAL and 57 to placebo. Overall, the incidence of severe mucositis was 51.7%, with 45.8% in the SAMITAL and 57.9% in the placebo arm (OR = 0.6; 95% CI: 0.3-1.3). After chemo-radiotherapy, patients randomized to SAMITAL reported significantly lower xerostomia, coughing and swallowing scores and a better quality of life. CONCLUSION: SAMITAL did not significantly reduce the incidence of severe mucositis in all studied populations. However, the lower rate of mucositis, together with a significantly better quality of life, suggested that a clinical benefit existed. This trial is registered with the EU Clinical Trials Register database, number 2012-002046-20, and with ClinicalTrials.gov, NCT01941992.

4.
Eur Arch Otorhinolaryngol ; 268(12): 1779-87, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21842202

RESUMO

Patients with head and neck squamous cell carcinoma (SCC) respond very differently to radiotherapy (RT). Since clinical factors cannot accurately predict its effects, biological parameters have been investigated, including tumor hypoxia. CD105 is a hypoxia-inducible glycoprotein emerging as a potential prognostic indicator for several solid malignancies. Angiogenin is upregulated under hypoxic conditions and supports primary and metastatic tumor growth. Epidermal growth factor receptor (EGFR) activation stimulates tumor proliferation and angiogenesis. The aim of the present study was to ascertain the prognostic importance of hypoxia-inducible factors (CD105, angiogenin) and EGFR in a series of patients who underwent primary surgery followed by RT for laryngeal SCC. 25 consecutive patients with laryngeal SCC given postoperative RT have been investigated. CD105, angiogenin, and EGFR immunohistochemical expressions in primary laryngeal SCCs have been evaluated also with image analysis. The recurrence rate was significantly higher in SCC patients with a CD105 expression >10.0% (P = 0.012) and their disease-free survival (DFS) was shorter (P = 0.044). Neither angiogenin (in the carcinoma cells or endothelial cells) nor EGFR expression were associated with the prognosis in our patients after primary surgery followed by RT for laryngeal SCC. CD105 should be studied as a potentially predictive biomarker for identifying laryngeal SCCs at higher risk of early recurrence after postoperative RT. Targeted anti-CD105 therapy associated with RT should also be investigated in patients with laryngeal SCCs characterized by high CD105 expression.


Assuntos
Antígenos CD/biossíntese , Carcinoma de Células Escamosas/mortalidade , Receptores ErbB/biossíntese , Neoplasias Laríngeas/mortalidade , Laringectomia , Receptores de Superfície Celular/biossíntese , Ribonuclease Pancreático/biossíntese , Idoso , Biomarcadores Tumorais/biossíntese , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Intervalo Livre de Doença , Endoglina , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Itália/epidemiologia , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/radioterapia , Neoplasias Laríngeas/cirurgia , Masculino , Estadiamento de Neoplasias , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências
5.
Anticancer Res ; 28(2B): 1383-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18505084

RESUMO

BACKGROUND: The purpose of this study was to evaluate the efficacy and toxicity of neo-adjuvant carboplatin and vinorelbine followed by concomitant chemoradiotherapy in patients > or =70 years of age or with Karnofsky performance status (PS) 70-80, diagnosed with locally advanced head and neck (H&N) or oesophageal carcinoma. PATIENTS AND METHODS: The treatment plan consisted of three courses of carboplatin AUC4 on day 1 and vinorelbine 25 mg/m2 on day 1 and 8, every 21 days, followed by chemoradiotherapy. Carboplatin 100 mg/m2 was delivered weekly for the duration of the radiation therapy (70 Gy, 2 Gy/daily). RESULTS: Thirty-five patients with an average age of 68 years (range 42-85, 16 patients > or =70 years) were treated. Twenty-seven patients (77.1%) responded to neo-adjuvant chemotherapy (2 complete and 25 partial responses). Haematological toxicity was grade 3-4 in 13 patients (37.2%), while gastrointestinal toxicity was grade 3-4 in 20 patients (57.1%). All the patients completed the chemoradiotherapy plan, with grade 4 mucositis plus febrile neutropenia in 3 patients (8.5%). Median time to progression (TTP) was 10.2 months, with 31.5% of patients being alive at two years. CONCLUSION: The regimen of neo-adjuvant carboplatin and vinorelbine followed by chemoradiotherapy is feasible and active in older (> or =70 years) or low PS (Karnofsky 70-80) patients, although toxicity is not negligible and long-term outcome remains poor.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Taxa de Sobrevida , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vimblastina/análogos & derivados , Vinorelbina
6.
Lung Cancer ; 57(1): 89-95, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17403553

RESUMO

BACKGROUND: Trimodality therapy seems to be the best treatment for malignant pleural mesothelioma (MPM). A large experience served to evaluate the efficacy of surgery followed by adjuvant chemo-radiotherapy. Trimodality therapy results have led us to test induction chemotherapy followed by EPP and adjuvant radiotherapy in stages I-III of MPM. The aim of our study was to evaluate the feasibility of this protocol and to estimate survival. METHODS: From 2000 to 2003, 21 patients with MPM (14 males and 7 females, median age 59 years) were enrolled in the prospective study. Induction chemotherapy consisted of Carboplatin (AUC 5mg/mL/min on Day 1) and Gemcitabine (1000mg/m(2) on Days 1, 8, 15) for three to four cycles. EPP was performed 3-5 weeks after induction therapy, while post-operative RT was given 4-6 weeks after operation. RESULTS: Ten patients received three cycles of chemotherapy, 10 patients received four cycles and 1 patient had two cycles. Grades 3-4 haematological toxicity occurred in eight (38.1%) patients. Chemotherapy response rate was: complete 0%, partial 33.3% and stable disease 66.7%. Seventeen (80.9%) out of 21 patients underwent EPP with no intra or post-operative mortality with an overall major and minor morbidity rate at 52.4%. Median survival was 25.5 months, with an overall 1, 3 and 5-year survival rate of 71, 33 and 19%, respectively. CONCLUSIONS: In MPM, the combined modality approach using the Carboplatin/Gemcitabine combination as induction chemotherapy is feasible, with good results in terms of survival and morbidity. Our results are similar to those of other studies using a heavier modality treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Mesotelioma , Neoplasias Pleurais , Pneumonectomia , Adulto , Idoso , Anemia/induzido quimicamente , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/toxicidade , Antineoplásicos/administração & dosagem , Antineoplásicos/toxicidade , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Carboplatina/administração & dosagem , Carboplatina/toxicidade , Terapia Combinada , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Desoxicitidina/toxicidade , Esquema de Medicação , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Leucopenia/induzido quimicamente , Masculino , Mesotelioma/tratamento farmacológico , Mesotelioma/patologia , Mesotelioma/radioterapia , Mesotelioma/cirurgia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neutropenia/induzido quimicamente , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/patologia , Neoplasias Pleurais/radioterapia , Neoplasias Pleurais/cirurgia , Pneumonectomia/estatística & dados numéricos , Doses de Radiação , Radioterapia Adjuvante , Análise de Sobrevida , Trombocitopenia/induzido quimicamente , Fatores de Tempo , Gencitabina
7.
Onco Targets Ther ; 9: 3671-81, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27382305

RESUMO

OBJECTIVES: If concurrent chemoradiotherapy cannot be performed, induction chemotherapy followed by radical-intent surgical treatment is an acceptable option for non primarily resectable non-small-cell lung cancers (NSCLCs). No markers are available to predict which patients may benefit from local treatment after induction. This exploratory study aims to assess the feasibility and the activity of multimodality treatment, including triple-agent chemotherapy followed by radical surgery and/or radiotherapy in locally advanced NSCLCs. METHODS: We retrospectively collected data from locally advanced NSCLCs treated with induction chemotherapy with carboplatin (area under the curve 6, d [day]1), paclitaxel (200 mg/m(2), d1), and gemcitabine (1,000 mg/m(2) d1, 8) for three to four courses, followed by radical surgery and/or radiotherapy. We analyzed radiological response and toxicity. Estimated progression-free survival (PFS) and overall survival (OS) were correlated to response, surgery, and clinical features. RESULTS: In all, 58 NSCLCs were included in the study: 40 staged as IIIA, 18 as IIIB (according to TNM Classification of Malignant Tumors-7th edition staging system). A total of 36 (62%) patients achieved partial response (PR), and six (10%) progressions were recorded. Grade 3-4 hematological toxicity was observed in 36 (62%) cases. After chemotherapy, 37 (64%) patients underwent surgery followed by adjuvant radiotherapy, and two patients received radical-intent radiotherapy. The median PFS and OS were 11 months and 23 months, respectively. Both PFS and OS were significantly correlated to objective response (P<0.0001) and surgery (P<0.0001 and P=0.002). Patients obtaining PR and receiving local treatment achieved a median PFS and OS of 35 and 48 months, respectively. Median PFS and OS of patients not achieving PR or not receiving local treatment were 5-7 and 11-15 months, respectively. The extension of surgery did not affect the outcome. CONCLUSION: The multimodality treatment was feasible, and triple-agent induction was associated with a considerable rate of PR. Patients achieving PR and receiving radical surgery or radiotherapy (53%) achieved a median OS of 4 years.

8.
Lung Cancer ; 100: 30-37, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27597278

RESUMO

BACKGROUND: Chemo-radiotherapy is standard of care in the treatment of unresectable stage III NSCLC. We aimed at assessing whether the addition of concurrent taxane-chemotherapy to thoracic irradiation following chemotherapy was able to improve treatment outcome. MATERIAL AND METHODS: In PITCAP trial, patients with unresectable stage III NSCLC were randomized to receive 2 cycles of platinum-paclitaxel followed by 60-61.2Gy thoracic irradiation (control arm) or by same radiotherapy with concomitant weekly paclitaxel (experimental arm). A literature-based meta-analysis including all studies with same design was also performed. RESULTS: At the time of the second interim analysis, when 151 patients were randomized, accrual was terminated. With a median follow-up of 6.1 years, median survival was 13.2 vs 15.1 months, with a 3-year survival rate of 19.5 vs 21.2% in the control and experimental arm, respectively (HR: 0.97; 95% CI 0.69-1.36; p=0.845). Treatment toxicity was manageable in both arms. The meta-analysis of 5 trials (n=866) confirmed the lack of a meaningful effect on 1-year overall survival of a taxane added concurrently to radiotherapy. CONCLUSIONS: These results do not support a meaningful survival benefit with the addition of single agent taxane given concurrently to radiotherapy after platinum-based induction in locally advanced NSCLC.


Assuntos
Antineoplásicos/administração & dosagem , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Terapia Combinada/métodos , Metanálise como Assunto , Paclitaxel/administração & dosagem , Taxoides/administração & dosagem , Adulto , Idoso , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Carboplatina/uso terapêutico , Feminino , Humanos , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/uso terapêutico , Taxa de Sobrevida , Taxoides/uso terapêutico , Resultado do Tratamento
9.
Interact Cardiovasc Thorac Surg ; 20(6): 805-11; discussion 811-2, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25757477

RESUMO

OBJECTIVES: Pancoast tumour is a rare neoplasia in which the optimal therapeutic management is still controversial. The traditional treatment of Pancoast tumour (surgery, radiotherapy or a combination of both) have led to an unsatisfactory outcome due to the high rate of incomplete resection and the lack of local and systemic control. The aim of the study was to determine the efficacy of the trimodality approach. METHODS: Fifty-six patients (male/female ratio: 47/9, median age: 64 years) in stage IIB to IIIB were treated during a period between 1994 and 2013. Induction therapy consisted of 2-3 cycles of a platinum-based chemotherapy associated with radiotherapy (30-44 Gy). After restaging, eligible patients underwent surgery 2 to 4-week post-radiation. RESULTS: Thirty-two (57.1%) patients were cT3 and 24 (42.9%) cT4, 47 (83.9%) were N0 and 9 (16.1%) N+. Forty-eight (85.7%) patients underwent R0 resection and 10 (17.9%) had a complete pathological response (CPR). Thirty-day mortality rate was 5.4%, major surgical complications occurred in 6 (10.7%) patients. At the end of the follow-up, 17 (30.4%) patients were alive and 39 (69.6%) died (29 for cancer-related causes), with an overall 5-year survival of 38%. At statistical analysis, stage IIB (P = 0.003), R0 resection (P = 0.03), T3 tumour (P = 0.002) and CPR (P = 0.01) were significant independent predictors of better prognosis. CONCLUSIONS: This combined approach is feasible, and allows for a good rate of complete resection. Long-term survival rates are acceptable, especially for early stage tumours radically resected. Systemic control of disease still remains poor, with distant recurrence being the most common cause of death.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia Adjuvante , Terapia Neoadjuvante , Síndrome de Pancoast/terapia , Pneumonectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia Adjuvante/efeitos adversos , Quimiorradioterapia Adjuvante/mortalidade , Fracionamento da Dose de Radiação , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/mortalidade , Estadiamento de Neoplasias , Síndrome de Pancoast/mortalidade , Síndrome de Pancoast/patologia , Pneumonectomia/efeitos adversos , Pneumonectomia/mortalidade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
10.
Radiother Oncol ; 109(2): 303-10, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23932151

RESUMO

BACKGROUND AND PURPOSE: Oropharyngeal mycosis (OPM) is a complication of radiotherapy (RT) treatments for head and neck (H&N) cancer, worsening mucositis and dysphagia, causing treatment interruptions and increasing overall treatment time. Prophylaxis with antifungals is expensive. Better patient selection through the analysis of prognostic factors should improve treatment efficacy and reduce costs. MATERIALS AND METHODS: A multicentre, prospective, controlled longitudinal study, with ethics committee approval, examined H&N cancer patients who were candidates for curative treatments with radio-chemotherapy. Patients were divided in groups according to OPM appearance: before the starting of RT (cases), during RT (new cases) and never (no cases). RESULTS: Of 410 evaluable patients, 20 were existing cases, 201 new cases and 189 did not report OPM. In our study OPM appears in 42.4% of people >70years and in 58.2% of younger individuals (p=0.0042), and in 68.6% of women versus 50.8% of men (p=0.0069). Mucositis and dysphagia were higher and salivation reduced among people with OPM (p<0.0000). Patients with OPM had longer hospitalization (p=0.0002) and longer (>12days) treatment interruptions (p=0.0288). CONCLUSIONS: Patients with OPM had higher toxicity and a greater number of long treatment interruptions. Analyses of prognostic factors can help clinicians understand OPM distribution and select patients with the highest probability of OPM for antifungal prophylaxis.


Assuntos
Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/efeitos adversos , Neoplasias de Cabeça e Pescoço/terapia , Micoses/etiologia , Doenças Faríngeas/etiologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Orofaringe/microbiologia , Estudos Prospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço
11.
Anticancer Res ; 32(12): 5393-9, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23225442

RESUMO

AIM: The objective of this study was the retrospective evaluation of tolerability and activity of pemetrexed with carboplatin (AC) or cisplatin (AP) as neoadjuvant chemotherapy in a consecutive series of patients with malignant pleural mesothelioma (MPM). PATIENTS AND METHODS: Patients with operable MPM received three cycles of AC or AP followed by surgery and radiotherapy. RESULTS: Since 2005, 51 patients have been treated with AC (27) and AP (24). We observed higher incidence of grade 3 anaemia, cumulative grade 2-3 asthenia and worsening of performance status in the AP group. Response to AC and AP were; complete: 4% vs. 0%, partial: 18% vs. 17%, stable disease: 74% vs. 79%, progressive disease: 4%; the resection rate was 81% vs. 79%. CONCLUSION: AC and AP are active and feasible neoadjuvant regimens. Progression-free survival, response, disease control and resection rate were similar in the two treatment groups. The lower tolerability to AP treatment could impair the clinical condition of patients undergoing surgery.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mesotelioma/tratamento farmacológico , Neoplasias Pleurais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Glutamatos/administração & dosagem , Glutamatos/efeitos adversos , Guanina/administração & dosagem , Guanina/efeitos adversos , Guanina/análogos & derivados , Humanos , Masculino , Mesotelioma/radioterapia , Mesotelioma/cirurgia , Pessoa de Meia-Idade , Terapia Neoadjuvante , Pemetrexede , Neoplasias Pleurais/radioterapia , Neoplasias Pleurais/cirurgia , Estudos Retrospectivos
12.
Lung Cancer ; 68(2): 228-33, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19632000

RESUMO

UNLABELLED: Superior sulcus tumour (SST) is an uncommon neoplasia whose optimal treatment remains controversial. Usually resected after induction RT or treated with definitive chemo-radiotherapy, it has recently aroused more interest because of preoperative chemo-radiotherapy. Treatment consisted of a platinum-based chemotherapy: carboplatin AUC 5 on days 1 and 22, combined with mitomycin-C 8 mg/m(2) on days 1 and 22, and vinblastine 4 mg/m(2) on days 1, 8, 22 and 29 (MVC) from 1994 to 1999, or combined with navelbine 25mg/m(2) on days 1, 8, 22 and 29 (NC), from 2000 to 2007. Radiotherapy was administered 5 days/week, 30 Gy in 10 fractions on days 22-35 (from 1994 to 1996), or 44 Gy in 22 fractions on days 22-52 (from 1997 to 2007). SURGERY was planned after 2-3 weeks since the completion of radiotherapy. Since 1994, 37 pts were treated with induction chemo-radiotherapy, 1 with induction radiotherapy only. Induction chemotherapy: 16 pts had MVC (43%) and 21 NC (57%); induction radiotherapy: 7 patients treated with MVC had 30 Gy/10F, 9 had 44 Gy/22F; all the patients treated with NC had 44 Gy/22F, but 2 of them did not complete radiotherapy because of early death (after 16 Gy/8F) and toxicity (after 38 Gy/19F). Grade 3-4 haematological toxicity of induction chemo-radiotherapy was found in 13 patients (35%); the most frequent non-haematological toxicities were constipation and oesophagitis. One complete, 18 partial and 8 minimal responses/stable disease were observed. Moreover, 1 progression disease and 1 early death occurred. SURGERY: 30 upper lobectomies (17 right, 13 left) and 4 segmentectomies, with chest wall resections, were performed (89% resection rate); 4 pts were not operated. Radical resections were achieved in 74% of the patients, with 5 pathologic complete remissions at resection. Twenty-seven patients (71%) had improvement of shoulder/arm pain. Median progression-free survival was 64 weeks and median survival was 148 weeks. The 5-year overall and progression-free survivals were 40% and 29%, respectively. In the multimodality treatment of SST, concurrent carboplatin-based chemotherapy plus radiotherapy were active and feasible without major toxicities. This resulted in high resectability rate and favourable progression-free and overall survival rates.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Pneumonectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carboplatina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimioterapia Adjuvante , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Mitomicina/uso terapêutico , Cuidados Pré-Operatórios , Radioterapia Adjuvante , Vimblastina/uso terapêutico
13.
Lasers Surg Med ; 39(5): 394-402, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17565719

RESUMO

PURPOSE: The role of photodynamic therapy (PDT) in the treatment of small cancers has been established in several clinical studies. Here, we report on the efficacy of PDT for early inoperable or recurrent non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: From June 1989 to November 2004, 40 patients with 50 NSCLC were treated with PDT. Twelve cases were inoperable for medical reasons and were staged as T1N0M0, and 28 had recurrent in situ carcinoma. Patients with residual disease after PDT received definitive radiotherapy and/or brachytherapy. Follow-up ranged from 6 to 167 months (median 43.59). Twenty of the 40 patients received i.v. injections of hematoporphyrin derivative (5 mg/kg), the other 20 had injections of porfimer sodium (Photofrin, 2 mg/kg). An argon dye laser (630 nm wavelength, 200-300 J/cm2) was used for light irradiation in 24 of the 40 patients, a diode laser (Diomed, 630 nm wavelength, 100-200 J/cm2) in the other 16. RESULTS: PDT obtained a 72% complete response (CR) rate (36/50 treated lesions), that is 27 CR among the 37 Tis carcinomas and 9 among the 13 T1 cases. Kaplan-Meier curves showed a mean overall survival (OS) of 75.59 months (median 91.4 months). Two- and 5-year OS rates were 72.78% and 59.55%. The mean and median survival rates for patients with Tis stage were 86.5 and 120.4 months, respectively (standard error 9.50) and for patients with T1 disease they were 45.78 and 35.71 months, respectively; the difference was statistically significant (P = 0.03). No severe early or late PDT-related adverse events were recorded. CONCLUSIONS: PDT is effective in early primary or recurrent NSCLC, resulting in a CR rate of 72%. The incorporation of PDT in standard clinical practice, in combination with radiotherapy, warrants further investigation.


Assuntos
Carcinoma in Situ/tratamento farmacológico , Carcinoma in Situ/mortalidade , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Fotoquimioterapia , Idoso , Carcinoma in Situ/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Éter de Diematoporfirina/uso terapêutico , Intervalo Livre de Doença , Feminino , Seguimentos , Derivado da Hematoporfirina/uso terapêutico , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Fármacos Fotossensibilizantes/uso terapêutico , Estudos Retrospectivos , Taxa de Sobrevida
14.
Cancer ; 97(11): 2791-7, 2003 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-12767092

RESUMO

BACKGROUND: Malignant pleural mesothelioma (MPM) is increasing rapidly worldwide. Currently, pemetrexed plus cisplatin chemotherapy showed a survival advantage versus cisplatin alone. No impact on patient survival of surgery, radiotherapy, or their combination has been demonstrated. METHODS: Eight centers in northeastern Italy participated in a Phase II multicenter study. Chemotherapy was comprised of carboplatin area under the concentration-time curve 5 on Day 1 and gemcitabine 1000 mg/m(2) on Days 1, 8, and 15. This cycle was repeated every 4 weeks. RESULTS: Between July 1996 and September 2000, 50 patients were treated. Of the sample, 68% were males, 88% had a Eastern Cooperative Oncology Group performance status score of 0-1, 56% had Stage I-II disease, 68% had epithelioid histology, and 62% had no previous treatments. The delivered dose intensity of gemcitabine was 617 mg/m(2) per week, which was 82% of the planned dose (750 mg/m(2) per week). For carboplatin, the delivered dose intensity was 80 mg/m(2) per week. Overall, 44% of 15th day doses were omitted or reduced. Twenty-six percent of the patients had partial responses (95% confidence interval: 15-40%) and 24% had disease progression. None of the patients had complete responses. The median response duration was 55 weeks (range, 13-113 weeks). Patients had good clinical benefit. For example, 46% had improved dyspnea, 40% improved in weight, and 26% experienced pain reduction. Patients developed Grade 3-4 leukopenia during 18 cycles (11%) of chemotherapy. Grade 3-4 thrombocytopenia occurred more frequently, i.e., there were 24 episodes (15%) among 17 patients. Grade 3 anemia developed among patients during eight cycles (5%). None of the patients developed Grade 3-4 nonhematologic toxicity. The median survival of this sample of patients was 66 weeks with 53%, 30%, and 20% of patients alive at 1, 2, and 3 years, respectively. The median progression-free survival period was 40 weeks. CONCLUSIONS: The gemcitabine/carboplatin combination is a valid option in the treatment of MPM due to its acceptable toxicity profile, the good response rate, and the clinical benefit to patients. Minor adjustments in schedule (3-week cycles instead of 4-week cycles) would permit a more optimal treatment administration.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Mesotelioma/tratamento farmacológico , Neoplasias Pleurais/tratamento farmacológico , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Desoxicitidina/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Masculino , Mesotelioma/patologia , Pessoa de Meia-Idade , Neoplasias Pleurais/patologia , Taxa de Sobrevida , Gencitabina
15.
J Natl Cancer Inst ; 96(22): 1714-7, 2004 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-15547184

RESUMO

In 1986, we initiated a multicenter, randomized trial to compare induction chemotherapy with cisplatin and 5-fluorouracil followed by locoregional treatment (surgery and radiotherapy or radiotherapy alone) with locoregional treatment alone in patients with head and neck squamous cell carcinoma. Here we report the long-term results of the trial. A total of 237 patients with nonmetastatic stage III or IV head and neck carcinoma were randomly assigned to receive four cycles of neoadjuvant chemotherapy followed by locoregional treatment (group A) or locoregional treatment alone (group B). Among all patients, overall survival at 5 and 10 years was 23% (95% confidence interval [CI] = 15.3% to 30.9%) and 19% (95% CI = 11.6% to 26.4%), respectively, for those in group A and 16% (95% CI = 9.6% to 23.4%) and 9% (95% CI = 3.5% to 14.7%), respectively, for those in group B (P = .13). Among operable patients, we observed no difference between group A and group B in overall survival at 5 and 10 years (group A, 31% [95% CI = 14.9% to 47.3%] and 22.7% [95% CI = 7.1% to 38.3%], respectively; group B, 43.3% [95% CI = 25.6% to 61.0%] and 14.2% [95% CI = 0.1% to 28.3%], respectively; P = .73). Among inoperable patients, overall survival at 5 and 10 years was 21% (95% CI = 12.3% to 30.1%) and 16% (95% CI = 7.7% to 23.9%), respectively, for group A and 8% (95% CI = 1.5% to 12.3%) and 6% (95% CI = 0.1% to 9.1%), respectively, for group B (log-rank P = .04). Four cycles of neoadjuvant chemotherapy is a promising approach for treating patients with inoperable advanced head and neck cancer but not for treating patients with operable disease.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Terapia Neoadjuvante/métodos , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Quimioterapia Adjuvante , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Razão de Chances , Radioterapia Adjuvante , Indução de Remissão , Análise de Sobrevida , Resultado do Tratamento
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