RESUMO
BACKGROUND: Treatment with fluoropyrimidines and concomitant long-course external radiotherapy (RTE) is the standard of care in locally advanced rectal cancer (LARC) preoperative chemoradiation. A randomized phase II study (RaP/STAR-03) was conducted that aimed to evaluate the activity and safety of the monoclonal antibody anti-epidermal growth factor receptor panitumumab as a single agent in combination with radiotherapy in low-risk LARC preoperative treatment. MATERIALS AND METHODS: Patients had adenocarcinoma of the mid-low rectum, cT3N- or cT2-T3N+, KRAS wild-type status, and negative circumferential radial margin. Panitumumab was administered concomitant to RTE. Rectal surgery was performed 6-8 weeks after the end of preoperative treatment. The adjuvant chemotherapy regimen was FOLFOX. The primary endpoint was the pathologic complete response (pCR) rate. The sample size was calculated using Simon's two-stage design. A pCR of 16% was considered to qualify the experimental treatment for further testing. RESULTS: Ninety-eight patients were enrolled in 13 Italian centers from October 2012 to October 2015. Three panitumumab infusions were administered in 92 (93.4%) patients. The RTE compliance was median dose 50.4 Gy; ≥28 fractions in 82 (83.7%) patients. Surgical treatment was performed in 92 (93.9%) patients, and no severe intraoperative complications were observed. A pCR was observed in 10 (10.9%) patients (95% confidence interval, 4.72%-17.07%). Pathological downstaging occurred in 45 (45.9%) patients. Grade 3 toxicities were observed in 22 (22.3%) patients, and the common adverse events were skin rash in 16 (16.3%) patients. No grade 4 toxicities were reported. CONCLUSION: The pCR rate (our primary endpoint), at only 10.9%, did not reach the specified level considered suitable for further testing. However, the analysis showed a good toxicity profile and compliance to concomitant administration of panitumumab and RTE in preoperative treatment of LARC. The pCR evaluation in all wild-type RAS is ongoing. IMPLICATIONS FOR PRACTICE: The aim of the RaP/STAR-03 study was to evaluate the activity and safety of monoclonal antibody anti-epidermal growth factor receptor (EGFR) panitumumab as a single agent without chemotherapy in low-risk, locally advanced rectal cancer (LARC) preoperative treatment. Nevertheless, the use of panitumumab in combination with radiotherapy in preoperative treatment in patients with KRAS wild type and low-risk LARC did not reach the pathologic complete response primary endpoint. This study showed a good toxicity profile and compliance to combination treatment. Further analysis of NRAS and BRAF on tissue and circulating levels of the EGFR ligands and vascular factors (soluble vascular endothelial growth factor, E-selectin) may provide insight on the potential molecular pathways involved in the anti-EGFR response.
Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Quimiorradioterapia/métodos , Panitumumabe/uso terapêutico , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Panitumumabe/farmacologia , Cuidados Pré-OperatóriosRESUMO
Lung cancer is the tumor with the highest incidence in males worldwide and the most common cause of death from cancer overall; its high mortality is mostly due to its propensity to spread to other organs through lymphatic and blood vessels in spite of proper treatment. Bladder metastases from lung cancer are rare, with only 11 cases having been reported, all in recent years. This review aims to discuss some critical points regarding this uncommon condition, namely: (a) lung and bladder tumors share similar etiologic features; (b) almost all bladder metastases from lung cancer arise from lung adenocarcinomas; (c) cytology and superficial bladder biopsy may be falsely negative, since the neoplastic cells coming through the hematogenous route are typically located in the lamina propria and/or muscularis propria of the bladder wall; and (d) the differential diagnosis with primary bladder adenocarcinoma as well as primary and secondary small-cell carcinomas may be challenging. Though no definite conclusions can be drawn regarding treatment, we herein propose a practical algorithm to manage such patients based on available data.
Assuntos
Neoplasias Pulmonares/patologia , Neoplasias da Bexiga Urinária/secundário , HumanosRESUMO
Until recently, only therapy with docetaxel and prednisone has been shown to prolong survival in men with hormonorefractory metastatic prostate cancer. With approvals of sipuleucel-T, cabazitaxel, and abiraterone acetate, all based on improvement in overall survival, the scenary for management of men with metastatic prostate cancer has dramatically changed. Abiraterone acetate was developed to specifically inhibit cytochrome P450 (CYP)17A1, which is an essential enzyme in the biosynthesis of testosterone. In the phase III, the trial treatment with abiraterone acetate plus prednisone prolongs overall survival relative to prednisone alone in patients with metastatic castration-resistant prostate cancer who have disease progression after treatment with docetaxel and associated with an acceptable tolerability profile, which was generally similar to that of the placebo plus prednisone group. However, adverse events resulting from elevated mineralocorticoid levels because of CYP17A1 inhibition, fluid retention and oedema, hypokalaemia, hypertension occurred in significantly more in abiraterone acetate plus prednisone than in placebo plus prednisone.
Assuntos
Androstenóis/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Esteroide 17-alfa-Hidroxilase/antagonistas & inibidores , Androstenos , Androstenóis/farmacologia , Antineoplásicos Hormonais/farmacologia , Resistencia a Medicamentos Antineoplásicos , Humanos , Masculino , Prednisona/administração & dosagem , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/patologia , Resultado do TratamentoRESUMO
Type 1 neurofibromatosis (NF1) is an autosomal dominant disorder characterized by multiple forms of neural crest cell proliferation. Associated venous malformations are extremely rare. We present a case of a giant thrombosed internal jugular aneurysm with brachiocephalic vein thrombosis in an NF1 patient. Surgical correction required prophylactic left brachiocephalic vein ligation, aneurysm evacuation, and proximal jugular vein ligation. Extreme vein friability caused severe intraoperative bleeding. Vein wall histology confirmed neurofibromatosis infiltration. Jugular vein aneurysm and infiltration in NF1, although exceedingly rare, can pose a serious threat to the patient during surgical correction, with major vessel thrombosis enhancing morbidity and mortality.
Assuntos
Aneurisma Roto/etiologia , Veias Jugulares , Neurofibromatose 1/complicações , Trombose Venosa/etiologia , Aneurisma Roto/diagnóstico , Aneurisma Roto/cirurgia , Feminino , Humanos , Veias Jugulares/diagnóstico por imagem , Veias Jugulares/patologia , Veias Jugulares/cirurgia , Ligadura , Pessoa de Meia-Idade , Neurofibromatose 1/diagnóstico , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares , Trombose Venosa/diagnóstico , Trombose Venosa/cirurgiaRESUMO
Schwannomas are degenerate peripheral nerve sheath tumors that very rarely occur in the retroperitoneum. They are usually benign than malignancy is very rare and is usually observed in patients with von Recklinghausen disease. We report a case of female adult patient who presented with vague abdominal discomfort. The preoperative diagnosis was difficult and the treatment was complete surgical excision. The patient is with no evidence of recurrence more than four years after surgery.
Assuntos
Neurilemoma , Neoplasias Retroperitoneais , Feminino , Humanos , Pessoa de Meia-Idade , Neurilemoma/diagnóstico , Neoplasias Retroperitoneais/diagnósticoRESUMO
PURPOSE: There is no consensus on the use of cetuximab in elderly patients with metastatic colorectal cancer. To this end, a survey was carried in 17 Italian oncology centers. METHODS: The centers answered a 29-item questionnaire structured as follows: (i) demographic characteristics; (ii) medical history; (iii) assessment of RAS/BRAF mutations and DPD/UGT polymorphism before treatment; (iv) treatment schemes and side effects; (v) geriatric assessment and customization of treatment. RESULTS: One-third of patients are over 80 years old. The RAS/BRAF mutational status is not primarily evaluated by 17.6% of the centers, while DPD and UGT polymorphism is not evaluated by 82.4% and 76.5% of the centers. The most common therapeutic scheme is cetuximab/FOLFIRI and diarrhea is the main cause of suspension/reduction of treatment. The 70% of centers use systemic tetracyclines for skin toxicity. The 23.5% of the centers do not carry out any geriatric evaluation before the start of the therapy and those who perform it prefer the G8 (70.6%) and VES-13 (29.4%) scales. CONCLUSIONS: Greater efforts should be made to improve the evaluation of the patient both about mutational and genetic procedures with geriatric evaluation. As for cetuximab in elderly patients, randomized studies are needed to provide guidance to physicians.
Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Institutos de Câncer/estatística & dados numéricos , Cetuximab/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cetuximab/efeitos adversos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Avaliação Geriátrica/estatística & dados numéricos , Pesquisas sobre Atenção à Saúde , Humanos , Itália , Masculino , Metástase Neoplásica , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas ras/genéticaRESUMO
INTRODUCTION: The aim of this study is to evaluate the long-term respiratory outcome of patients who underwent pneumonectomy for non-small cell lung cancer (NSCLC), analysing functional tests. MATERIALS AND METHODS: Twenty-seven consecutive patients who were candidates for pneumonectomy performed spirometry before and at least 24 months after surgery in the same laboratory. Diffusion of carbon monoxide and the most common dynamic and static lung volumes were evaluated in percentage of predicted and compared. RESULTS: A significant inverse correlation was observed between the preoperative FEV1 (%) and FVC (%) and their postoperative loss, respectively r=-641 (p<0.0001) and r=-789 (p<0.0001). Also the correlation between the RV/TLC ratio and the FEV1 loss confirmed a better postoperative outcome in patients with major airway obstruction (p=0.02). To investigate these data, the series were divided into two groups: group A included BPCO patients with a FEV1 lower than 80%, the others were considered group B. Group B showed a significant major postoperative FEV1 (%) and FVC (%) impairment, 31% versus 12%, p=0.005, and FVC (%) loss, 37% versus 16% (p=0.02), meanwhile group A showed a significant major postoperative RV (%) reduction, 43% versus 17%, p=0.03. Despite being significantly higher preoperatively in BPCO patients, the RV% becomes similar between the two groups in the postoperative. CONCLUSIONS: In our experience patients with major preoperative airway obstruction who underwent pneumonectomy had lower impairment in FEV1% at almost one year after surgery than those with normal respiratory function. The resection of a certain amount of non-functional parenchyma associated with the mediastinal shift, with an improvement of the chest cavity for the remaining lung, could give a reduction volume effect in BPCO/emphysematous patients.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Volume Expiratório Forçado , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Idoso , Dióxido de Carbono/sangue , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Feminino , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Pressão Parcial , Período Pós-Operatório , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Resultado do Tratamento , Capacidade VitalRESUMO
PURPOSE: We performed this phase III study to compare the irinotecan, leucovorin (LV), and fluorouracil (FU) regimen (FOLFIRI) versus the oxaliplatin, LV, and FU regimen (FOLFOX4) in previously untreated patients with advanced colorectal cancer. PATIENTS AND METHODS: A total of 360 chemotherapy-naive patients were randomly assigned to receive, every 2 weeks, either arm A (FOLFIRI: irinotecan 180 mg/m(2) on day 1 with LV 100 mg/m(2) administered as a 2-hour infusion before FU 400 mg/m(2) administered as an intravenous bolus injection, and FU 600 mg/m(2) as a 22-hour infusion immediately after FU bolus injection on days 1 and 2 [LV5FU2]) or arm B (FOLFOX4: oxaliplatin 85 mg/m(2) on day 1 with LV5FU2 regimen). RESULTS: One hundred sixty-four and 172 patients were assessable in arm A and B, respectively. Overall response rates (ORR) were 31% in arm A (95% CI, 24.6% to 38.3%) and 34% in arm B (95% CI, 27.2% to 41.5%; P = .60). In both arms A and B, median time to progression (TTP; 7 v 7 months, respectively), duration of response (9 v 10 months, respectively), and overall survival (OS; 14 v 15 months, respectively) were similar, without any statistically significant difference. Toxicity was mild in both groups: alopecia and gastrointestinal disturbances were the most common toxicities in arm A; thrombocytopenia and neurosensorial were the most common toxicities in arm B. Grade 3 to 4 toxicities were uncommon in both arms, and no statistical significant difference was observed. CONCLUSION: There is no difference in ORR, TTP, and OS for patients treated with the FOLFIRI or FOLFOX4 regimen. Both therapies seemed effective as first-line treatment in these patients. The difference between these two combination therapies is mainly in the toxicity profile.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Neoplasias Colorretais/patologia , Progressão da Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Infusões Intravenosas , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: The combination of cisplatin (CDDP) and 5-Fluorouracil (5-FU) is a standard regimen for the treatment of recurrent and metastatic head and neck squamous cell carcinoma (HNSCC). This combination shows a relevant toxicity and new chemotherapy associations with a more favourable toxicity profile are awaited. Carboplatin (CB) is a platinum derivative with less toxicity than CDDP. Raltitrexed (R) is a potent and specific thymidylate synthase inhibitor with activity comparable to that of 5-FU in colorectal cancer; moreover, it showed activity as a single agent in HNSCC. MATERIALS AND METHODS: Since 2001, a multicentre, phase II trial has been underway to evaluate the efficacy and toxicity of the CB+R combination in untreated patients with recurrent or metastatic HNSCC. Thirty-two patients were enrolled and included in an intent-to-treat analysis. Toxicity was graded according to NCI criteria. Patients had a histo/cytologically proven recurrent or metastatic HNSCC; patients with locally advanced disease not amenable to CDDP+5-FU treatment were also included. Patients had to be >18 years old with ECOG PS of 0-2 and adequate bone marrow, renal and liver functions. CB (AUC 5) and R (3 mg/m2) were administered intravenously every 3 weeks. The median age was 62 years (range 43-71), 29 M/3 F. The median PS was 1 (0-2). Twelve patients were staged III and 20 were metastatic (10 recurrent). The oral cavity/oropharynx were the primary site in 20 patients and the larynx in 10 patients. The median number of cycles delivered was 3, while globally 115 cycles were administered. The median time to progression was 4.2 months and median duration of survival was 9.8 months. RESULTS: Seven patients achieved a partial response (22%), 10 patients showed a stable disease (31%), while 13 patients (48%) had progressive disease. Eight patients (25%) had a G 3-4 neutropenia, while G 3-4 anaemia was observed in 2 patients and thrombocytopenia in 1 patient. No extrar haematological G 3-4 toxicities were observed. A persistent G 2 hepatic toxicity led a patient to drop out from the study. CONCLUSION: In our phase II trial, CB in combination with R showed a moderate activity with safe administration on an outpatient basis.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Taxa de Sobrevida , Tiofenos/administração & dosagem , Tiofenos/efeitos adversosRESUMO
BACKGROUND: Docetaxel (DCT), a semisynthetic taxoid, has demonstrated cytotoxic activity against gastric cancer in early phase II studies producing an overall response rate of 17-24%. The Gruppo Oncologico Italia Meridionale (G.O.I.M.) started a confirmatory multicenter phase II trial to evaluate the clinical activity and toxicity of single agent TXT in the treatment of advanced gastric cancer patients who had failed a first-line chemotherapy. MATERIALS AND METHODS: Thirty patients with advanced gastric carcinoma refractory to first-line ECF or PELF chemotherapy were treated with DCT administered at the dosage of 100 mg/mq given as a 1-hour i.v. infusion every three weeks. All patients received a premedication with dexamethasone 8 mg i.v. 12 hours and 1 hour before, and 12 hours after DCT administration. Granulocyte colony stimulating factor was employed in case of febrile neutropenia as needed. The first evaluation of disease status was planned after three cycles. RESULTS: We observed 5 partial responses without any complete response for an overall response rate of 17% (95% CI = 6-36%, intent-to-treat analysis). Nine patients showed stable disease and 14 patients progressed. The duration of objective partial responses were 5, 6, 6, 9 and 12 months, respectively. The median overall survival was 6 months and the 1-year survival rate was 20.6%. No chemotherapy-related toxic death was observed. Haematological grade 3-4 side-effects were respectively: anemia (7%), leucopenia (7%) and neutropenia (18%); in 13 patients (45%) G-CSF was employed to avoid severe leukopenia. CONCLUSION: This multinstitutional single-step phase II study confirms that single-agent docetaxel is active in advanced gastric cancer progressing after first-line chemotherapy. The most frequent toxicity is neutropenia, which may be managed by G-CSF and/or dose adjustments. Docetaxel is therefore worthy of further study in combination with other active drugs.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Taxoides/uso terapêutico , Adulto , Idoso , Antineoplásicos Fitogênicos/efeitos adversos , Docetaxel , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Terapia de Salvação , Taxoides/efeitos adversosRESUMO
The aim of this study was to assess which prognostic factors could influence survival in surgically treated stage IA non-small cell lung cancer. The records of 224 consecutive patients with pathological stage IA after radical surgery were reviewed retrospectively. Overall 1, 3 and 5-year survival rates were 89%, 76%, and 66%. Nearly half of the deaths were unrelated to the original cancer. There was no difference in survival attributable to preoperative pulmonary function, age at operation, or extent of resection. However, patients with limited resections had a higher rate of local recurrence. Survival was better with a smaller size of tumor (= 2 cm), in the female sex, and in cases of bronchoalveolar adenocarcinoma.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Neoplasias Ósseas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/cirurgia , Feminino , Seguimentos , Humanos , Incidência , Itália/epidemiologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Procedimentos Cirúrgicos Torácicos , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of this study was to evaluate the activity and toxicity of a combination regimen of CPT-11 and mitomycin-c as second-line chemotherapy for pretreated patients with advanced, metastatic, or both, gastric adenocarcinoma. MATERIALS AND METHODS: Patients with pretreated metastatic disease or early relapsed after adjuvant chemotherapy were enrolled. Entry criteria included histologic/cytologic diagnosis of gastric adenocarcinoma, age 18 to 75 years, performance status > or =70 (Karnofsky scale), bi-dimensionally measurable disease. Patients received CPT-11 and mitomycin-c at the dosage of 150 mg/m2 on days 1 and 15, and 8 mg/m2 on day 1, respectively, every 4 weeks. The disease evaluation was done every 3 cycles. RESULTS: Among the 38 patients we observed, 1 (3%) complete response and 11 (29%) partial responses for an overall response rate of 32% according to an intent-to-treat analysis. The median duration of response was 6.5 months. The median time to progression was 4 months with a median overall survival 8 months. All patients were evaluable for toxicity and the only grade 3-4 observed toxicities were leukopenia (8%), neutropenia (21%), and anemia (5%). CONCLUSIONS: The combination of CPT-11 and mitomycin-c is an active and well tolerated second-line treatment in pretreated gastric cancer patients. Further studies are needed to test its role in first-line treatment.