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1.
Crit Rev Oncol Hematol ; 188: 104056, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37301272

RESUMO

Immune checkpoint inhibitors (ICIs) have revolutionized lung cancer management improving overall survival and providing durable responses with a favorable toxicity profile. New questions have emerged regarding the efficacy and safety of immunotherapy among older adults, typically underrepresented in clinical trials. Several factors have to be taken into account in order to reduce the realistic risk of over or under-treatment of this growing subgroup of patients. In this perspective, geriatric assessment and screening tools should be implemented in clinical practice; moreover older patients' inclusion into adapted-designed clinical trials should be promoted. In this review, we discuss immunotherapy activity in advanced non-small cell lung cancer (NSCLC) older patients, the role of the comprehensive geriatric assessment, treatment toxicity and its management with a focus on future perspectives in this rapidly evolving scenario.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Idoso , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Imunoterapia , Inibidores de Checkpoint Imunológico/uso terapêutico
2.
Lung Cancer ; 140: 71-79, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31884129

RESUMO

OBJECTIVES: Molecular diagnostics and care of non-small cell lung cancer (NSCLC) are continuously evolving. Few data document the current strategies to manage advanced NSCLC patients beyond progression in clinical practice. PATIENTS AND METHODS: Be-TeaM is an Italian multi-center observational study conducted on consecutive EGFR-mutated stage IV NSCLC patients, progressed during/after a first-line EGFR-TKI. It consists of a retrospective phase, from first-line EGFR-TKI therapy start until study entry (i.e. beginning of the diagnostic process), and a prospective phase, until treatment choice or for 3 months if no therapy was prescribed. Primary objective was to describe the diagnostic and therapeutic approaches adopted after progression in a real-world setting. RESULTS: Of 308 patients enrolled in 63 centers from July 2017 to June 2018, 289 were included in the analysis. In first line, 53.3 % received gefitinib, 32.5 % afatinib and 14.2 % erlotinib. The testing rate (i.e. rate of all patients undergone any biopsy -liquid and/or tissue- for the T790 M detection) was 90.7 %, with liquid biopsy being the most frequently executed. Of 262 biopsied patients, 64.5 % underwent only 1 liquid biopsy, 10.7 % only 1 tissue biopsy and 18.3 % >1 biopsy, both liquid and solid in 85.4 %. The T790M positivity rate was 45.3 %; of 166 patients undergone only a liquid biopsy and tested for the mutation, 39.8 % were T790M+ and 60.2 % T790M-/undetermined. By the observation end, 87.9 % patients had a post-progression treatment chosen, osimertinib being the most frequent among the T790M+. CONCLUSION: Be-TeaM provides the first snapshot of current practices for the management of NSCLC patients beyond progression in Italy; in clinical practice, assessing the T790M status is not always feasible.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Terapia de Alvo Molecular , Inibidores de Proteínas Quinases/uso terapêutico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Idoso , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Metástase Neoplásica , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida
3.
Cancers (Basel) ; 11(10)2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31557965

RESUMO

The ICARUS trial is a phase II, open label, multicenter, single arm study conducted to investigate the efficacy, safety, and tolerability of a rechallenge treatment with the first-generation tyrosine kinase inhibitor (TKI) gefitinib in advanced non-small-cell lung cancer (NSCLC) patients carrying activating mutations of the epidermal growth factor receptor (EGFR). The ICARUS trial enrolled 61 patients who were rechallenged with gefitinib at progression after second-line chemotherapy. Serum-derived circulating cell-free DNA (cfDNA) collected before the rechallenge from a cohort of 29 patients, was retrospectively analyzed for the EGFR exon 19 deletions and for the p.L858R and p.T790M single nucleotide variants (SNV). The analysis of cfDNA detected the same EGFR activating mutation reported in the tumor tissue in 20/29 patients, with a sensitivity of 69%. Moreover, a p.T790M variant was found in 14/29 patients (48.3%). The median progression-free survival (PFS) was 2.7 months for p.T790M positive patients (CI 95% 1.4-3.1 months) versus 3.5 months for the p.T790M negative patients (CI 95% 1.6-5.3 months), resulting in a statistically significant difference (Long rank test p = 0.0180). These findings confirmed the role of the p.T790M mutation in the resistance to first-generation TKIs. More importantly, our data suggest that TKI rechallenge should be guided by biomarker testing.

4.
Lung Cancer ; 134: 121-126, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31319970

RESUMO

OBJECTIVES: Considering the frequent expression of somatostatine receptors, we designed the G04.2011 trial to investigate the efficacy of the somatostatine analogue lanreotide in maintenance for SCLC patients after response to standard treatment. MATERIALS AND METHODS: A multicenter, randomized, phase 3 trial was conducted in SCLC expressing somatostatine receptors at baseline Octreoscan, responding after platinum-based chemotherapy with/without radiotherapy. Patients were randomized 1:1 to receive maintenance lanreotide 120 mg subcutaneously every 28 days, up to 1 year or progression versus observation. Randomization was stratified according to stage (limited/extended, LD/ED). The primary end-point was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and safety. RESULTS: Seventy-one patients were randomly assigned (39 to lanreotide, 32 to observation) in 9 Italian institutions. Median PFS was 3.6 (95% CI 3.2-3.9) with lanreotide versus 2.3 months (95% CI 1.7-2.9) with observation (HR 1.51, 95% CI 0.90-2.50; P = 0.11). Stage was an independent predictor for PFS (HR 3.14, 95% CI 1.77-5.57; P < 0.0001). Median PFS was 7.0 (95% CI <1-13.5) with lanreotide versus 3.8 months (95% CI <1-8.6) with observation in LD (P = 0.21), and 3.0 (95% CI 2.2-3.8) versus 2.2 (95% 1.7-2.7) in ED (P = 0.19). Median OS was 9.5 (95% CI 4.8-14.3) with lanreotide versus 4.7 months (95% CI <1-16.6) with observation (P = 0.47). Treatment-related adverse events occurred in 28% of patients with lanreotide (grade 3 in two patients). CONCLUSION: Although survival outcomes were not significantly prolonged with lanreotide as a maintenance in SCLC expressing somatostatin receptors after response to standard treatment, lanreotide showed a slight PFS benefit in LD SCLC deserving further investigations.


Assuntos
Expressão Gênica , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Peptídeos Cíclicos/uso terapêutico , Receptores de Somatostatina/genética , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/genética , Somatostatina/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Itália , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Peptídeos Cíclicos/administração & dosagem , Peptídeos Cíclicos/efeitos adversos , Prognóstico , Modelos de Riscos Proporcionais , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/mortalidade , Somatostatina/administração & dosagem , Somatostatina/efeitos adversos , Somatostatina/uso terapêutico , Resultado do Tratamento
5.
Lung Cancer ; 134: 210-217, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31319983

RESUMO

OBJECTIVES: Despite the scant docetaxel's tolerability, second-line association with nintedanib still represents a standard-of-care for non-squamous non-small cell lung cancer (nsNSCLC), giving to rapidly-progressing patients the greatest survival advantage. The SENECA trial is a phase IIb, open-label, study evaluating whether nintedanib/docetaxel can be equally effective and safe regardless docetaxel schedule. MATERIALS AND METHODS: Recurrent nsNSCLC patients were stratified into cohort 1 and 2, according to relapse-time (within or over 3 months) from end of first-line chemotherapy. They were treated with docetaxel (T1: 33 mg/mq on days 1 and 8 in a 21-days cycle; T2: 75 mg/mq q3wks) plus nintedanib, allowing maintenance in case of disease-control. Primary endpoint was progression-free survival (PFS) by investigator's assessment; secondary endpoints: overall survival (OS), safety and quality-of-life. RESULTS: Between January 2016-April 2018, 212 patients were evaluated: 30 resulted screening-failures, 12 were excluded for lack of compliance. According to investigator's choice, 85 patients received T1 docetaxel and 85 T2; 138 (81.2%) were stratified in C1, 32 (18.8%) in C2, with a median relapse-time of 0.54 and 9.29 months, respectively. Baseline characteristics were balanced between groups. After 35.5 months follow-up, no survival differences appear between cohorts and treatments; toxicity seems to be slightly higher in T2, especially for chemotherapy-related events. Perception of quality-of-life remains stable and docetaxel schedule doesn't modify patients' load. CONCLUSION: The SENECA trial confirms efficacy of second-line nintedanib/docetaxel for nsNSCLC, regardless time of recurrence and docetaxel schedule; higher toxicities for q3wks docetaxel, without alterations in quality-of-life, have been described, underling the possibility, adopting the weekly schedule, to maintain efficacy with better tolerability.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Indóis/administração & dosagem , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Qualidade de Vida , Resultado do Tratamento
6.
Tumori ; 91(4): 314-6, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16277095

RESUMO

OBJECTIVE: The aim of this phase I study was to find the maximum tolerated dose of weekly docetaxel in association with estramustine in hormone-refractory prostate cancer. METHODS: Eleven patients with hormone-refractory prostate cancer were treated with escalating weekly doses of docetaxel (level I, 3 patients, 30 mg/m2; level II, 3 patients, 35 mg/m2, level III, 3 patients, 40 mg/mz; level IV, 2 patients, 45 mg/m2) associated with fixed dosage of estramustine (840 mg/day). RESULTS: In level I, there was only one episode of grade 3 neutropenia; grade 1 nausea and vomiting were registered in 1 patient; in 1 patient mild edema of the lower limbs was noted. In level II, grade 2 stomatitis and grade 1 sensory symptoms occurred in 1 patient, and grade 1 edema in 1 case. In level Ill, grade 2 edema was noted in 2 patients, damage to nails in 1 patient, asthenia in 1 patient, grade 1 neuropathy in 2 patients, and grade 1 nausea in 1 patient. In level IV, grade 2 edema was present in 1 patient, grade 3 edema in 1 patient, changes with fall of nails and grade 2 erythema of face in 2 patients, asthenia in 2 patients, grade 1 neuropathy in both patients. Nine patients had a more than a 50% decrease in PSA after 2 cycles of therapy. CONCLUSIONS: The results of the study suggest a good tolerability of weekly 35 Mg/m2 docetaxel in hormone-refractory prostate cancer in association with estramustine.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Próstata/tratamento farmacológico , Idoso , Docetaxel , Esquema de Medicação , Estramustina/administração & dosagem , Estramustina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Resultado do Tratamento
7.
Tumori ; 91(3): 237-40, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16206647

RESUMO

High-dose chemotherapy followed by autologous bone marrow or peripheral blood progenitor cell transplantation represents a recognized option in the treatment of solid tumors and hematologic diseases. Patients receiving high-dose chemotherapy are traditionally supported with parenteral nutrition with the aim to prevent malnutrition secondary to gastrointestinal toxicity and metabolic alterations induced by the conditioning regimens. Nevertheless, well-defined guidelines for its use in this clinical setting are lacking and there are several areas of controversy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Nutrição Parenteral , Transplante de Células-Tronco de Sangue Periférico , Guias de Prática Clínica como Assunto , Humanos , Neoplasias/terapia , Distúrbios Nutricionais/etiologia , Distúrbios Nutricionais/terapia , Fatores de Risco , Transplante Autólogo
9.
Tumori ; 91(2): 131-4, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15948539

RESUMO

BACKGROUND: Based on the results of previous phase I studies, in the current phase II trial we evaluated the efficacy and toxicity of cisplatin plus weekly docetaxel in the treatment of advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: The eligibility criteria for the study included newly diagnosed stage IIIB/IV NSCLC, age < or = 75 years, Eastern Cooperative Oncology Group performance status of 0-2, adequate organ functions, and signed informed consent. The chemotherapy regimen consisted of cisplatin, 80 mg/m2 on day 1, and docetaxel, 25 mg/m2 on days 1, 8 and 15 every 4 weeks. RESULTS: Between January 2002 and December 2003, 31 patients with NSCLC were enrolled in the study. An objective response rate of 40% (95% CI, 21-60) was obtained in 27 assessable patients. The median time to progression was 6.4 months (range, 2.5-26.3) and median overall survival was 10.01 months (range, 5-28.3). The regimen was well tolerated with no grade 4 toxicity. CONCLUSIONS: Cisplatin plus weekly docetaxel is an effective and well-tolerated regimen in chemo-naive patients with advanced NSCLC. A phase III study of weekly versus the conventional regimen of every three weeks should be conducted to compare the survival benefits, toxicity profile and quality of life.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/uso terapêutico , Taxoides/administração & dosagem , Taxoides/uso terapêutico , Idoso , Cisplatino/efeitos adversos , Progressão da Doença , Docetaxel , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida , Taxoides/efeitos adversos , Fatores de Tempo
13.
Anticancer Res ; 22(6B): 3647-52, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12552971

RESUMO

Glutathione S-Transferase (GST) is a phase II enzyme and catalyses reactions between glutathione and a variety of electrophilic compounds, including some environmental carcinogens. In man, at least 20 isoenzymatic forms of GST have been identified and many of them show genetically-based individual variability of enzyme activity. The GSTM1 and GSTT1 isoenzymes display several polymorphisms, including a homozygotic deletion, which have been associated with an increased risk for developing neoplastic diseases. There is geographical and ethnic variation in genotype frequencies for both genes. The available data suggest that cancer incidence varies amongst Italian regions, being higher in Northern that in Southern areas, though it is unknown whether this phenomenon is to be attributed to genetic and/or environmental factors. We performed a case-control study to evaluate the GSTM1 and GSTT1 polymorphisms in a series of cancer patients in Basilicata, a Southern Italian region, and in corresponding controls. The results obtained demonstrate that the occurrence of GST polymorphisms in the Basilicata population is not different from other Italian regions and suggest that the population attributable risk associated with these genotypes may be quite high. GSTM1 homozygous null genotype was associated with an increasing risk of cancer, especially in females. The strongest association was with colon and breast cancers. For the GSTT1 gene, the results obtained were suggestive of a decreased risk of cancer associated with the null genotype. Thus, similar studies on these and other susceptibility genes are warranted since they can help to identify susceptible subgroups of people who can be targeted for cancer prevention.


Assuntos
Glutationa Transferase/genética , Neoplasias/enzimologia , Neoplasias/genética , Polimorfismo Genético , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/enzimologia , Neoplasias da Mama/genética , Estudos de Casos e Controles , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/genética , Feminino , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Masculino , Neoplasias Ovarianas/enzimologia , Neoplasias Ovarianas/genética , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/genética
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