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1.
Ann Oncol ; 28(10): 2526-2532, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28961833

RESUMO

BACKGROUND: In the phase III LUX-Head & Neck 1 (LUX-H&N1) trial, second-line afatinib significantly improved progression-free survival (PFS) versus methotrexate in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Here, we evaluated association of prespecified biomarkers with efficacy outcomes in LUX-H&N1. PATIENTS AND METHODS: Randomized patients with R/M HNSCC and progression following ≥2 cycles of platinum therapy received afatinib (40 mg/day) or methotrexate (40 mg/m2/week). Tumor/serum samples were collected at study entry for patients who volunteered for inclusion in biomarker analyses. Tumor biomarkers, including p16 (prespecified subgroup; all tumor subsites), EGFR, HER2, HER3, c-MET and PTEN, were assessed using tissue microarray cores and slides; serum protein was evaluated using the VeriStrat® test. Biomarkers were correlated with efficacy outcomes. RESULTS: Of 483 randomized patients, 326 (67%) were included in the biomarker analyses; baseline characteristics were consistent with the overall study population. Median PFS favored afatinib over methotrexate in patients with p16-negative [2.7 versus 1.6 months; HR 0.70 (95% CI 0.50-0.97)], EGFR-amplified [2.8 versus 1.5 months; HR 0.53 (0.33-0.85)], HER3-low [2.8 versus 1.8 months; HR 0.57 (0.37-0.88)], and PTEN-high [1.6 versus 1.4 months; HR 0.55 (0.29-1.05)] tumors. Afatinib also improved PFS in combined subsets of patients with p16-negative and EGFR-amplified tumors [2.7 versus 1.5 months; HR 0.47 (0.28-0.80)], and patients with p16-negative tumors who were EGFR therapy-naïve [4.0 versus 2.4 months; HR 0.55 (0.31-0.98)]. PFS was improved in afatinib-treated patients who were VeriStrat 'Good' versus 'Poor' [2.7 versus 1.5 months; HR 0.71 (0.49-0.94)], but no treatment interaction was observed. Afatinib improved tumor response versus methotrexate in all subsets analyzed except for those with p16-positive disease (n = 35). CONCLUSIONS: Subgroups of HNSCC patients who may achieve increased benefit from afatinib were identified based on prespecified tumor biomarkers (p16-negative, EGFR-amplified, HER3-low, PTEN-high). Future studies are warranted to validate these findings. CLINICAL TRIAL REGISTRATION: NCT01345682.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/metabolismo , Metotrexato/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/metabolismo , Quinazolinas/administração & dosagem , Administração Intravenosa , Administração Oral , Afatinib , Antimetabólitos Antineoplásicos/administração & dosagem , Biomarcadores Tumorais/sangue , Biópsia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/patologia , Intervalo Livre de Doença , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Metástase Neoplásica , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Valor Preditivo dos Testes , Carcinoma de Células Escamosas de Cabeça e Pescoço
2.
Ann Oncol ; 27(8): 1585-93, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27084954

RESUMO

BACKGROUND: In the phase III LUX-Head & Neck 1 (LHN1) trial, afatinib significantly improved progression-free survival (PFS) versus methotrexate in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients progressing on/after platinum-based therapy. This report evaluates afatinib efficacy and safety in prespecified subgroups of patients aged ≥65 and <65 years. PATIENTS AND METHODS: Patients were randomized (2:1) to 40 mg/day oral afatinib or 40 mg/m(2)/week intravenous methotrexate. PFS was the primary end point; overall survival (OS) was the key secondary end point. Other end points included: objective response rate (ORR), patient-reported outcomes, tumor shrinkage, and safety. Disease control rate (DCR) was also assessed. RESULTS: Of 483 randomized patients, 27% (83 afatinib; 45 methotrexate) were aged ≥65 years (older) and 73% (239 afatinib; 116 methotrexate) <65 years (younger) at study entry. Similar PFS benefit with afatinib versus methotrexate was observed in older {median 2.8 versus 2.3 months, hazard ratio (HR) = 0.68 [95% confidence interval (CI) 0.45-1.03], P = 0.061} and younger patients [2.6 versus 1.6 months, HR = 0.79 (0.62-1.01), P = 0.052]. In older and younger patients, the median OS with afatinib versus methotrexate was 7.3 versus 6.4 months [HR = 0.84 (0.54-1.31)] and 6.7 versus 6.2 months [HR = 0.98 (0.76-1.28)]. ORRs with afatinib versus methotrexate were 10.8% versus 6.7% and 10.0% versus 5.2%; DCRs were 53.0% versus 37.8% and 47.7% versus 38.8% in older and younger patients, respectively. In both subgroups, the most frequent treatment-related adverse events were rash/acne (73%-77%) and diarrhea (70%-80%) with afatinib, and stomatitis (43%) and fatigue (31%-34%) with methotrexate. Fewer treatment-related discontinuations were observed with afatinib (each subgroup 7% versus 16%). A trend toward improved time to deterioration of global health status, pain, and swallowing with afatinib was observed in both subgroups. CONCLUSIONS: Advancing age (≥65 years) did not adversely affect clinical outcomes or safety with afatinib versus methotrexate in second-line R/M HNSCC patients. CLINICAL TRIAL REGISTRATION: NCT01345682 (ClinicalTrials.gov).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Metotrexato/administração & dosagem , Quinazolinas/administração & dosagem , Afatinib , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/patologia , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Metotrexato/efeitos adversos , Metástase Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Platina/administração & dosagem , Platina/efeitos adversos , Quinazolinas/efeitos adversos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Resultado do Tratamento
3.
Ann Oncol ; 25(1): 216-25, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24256848

RESUMO

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is the standard treatment for patients with unresectable, nonmetastatic locoregionally advanced squamous-cell carcinoma of the head and neck (LASCCHN). This randomized, open-label, phase III clinical trial compared the efficacy between standard CCRT and two different induction chemotherapy (ICT) regimens followed by CCRT. PATIENTS AND METHODS: Patients with untreated LASCCHN were randomly assigned to ICT (three cycles), with either docetaxel (Taxotere), cisplatin and 5-fluorouracil (TPF arm) or cisplatin and 5-fluorouracil (PF arm), followed by CCRT [7 weeks of radiotherapy (RT) with cisplatin 100 mg/m(2) on days 1, 22 and 43]; or 7 weeks of CCRT alone. The primary end points were progression-free survival (PFS) and time-to-treatment failure (TTF). RESULTS: In the intention-to-treat (ITT) population (n = 439), the median PFS times were 14.6 (95% CI, 11.6-20.4), 14.3 (95% CI, 11.8-19.3) and 13.8 months (95% CI, 11.0-17.5) at TPF-CCRT, PF-CCRT and CCRT arms, respectively (log-rank P = 0.56). The median TTF were 7.9 (95% CI, 5.9-11.8), 7.9 (95% CI, 6.5-11.8) and 8.2 months (95% CI, 6.7-12.6) for TPF-CCRT, PF-CCRT and CCRT alone, respectively (log-rank P = 0.90). There were no statistically significant differences for overall survival (OS). Toxic effects from ICT-CCRT were manageable. CONCLUSION: Overall, this trial failed to show any advantage of ICT-CCRT over CCRT alone in patients with unresectable LASCCHN.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeça e Pescoço/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Quimiorradioterapia , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Docetaxel , Fracionamento da Dose de Radiação , Feminino , Fluoruracila/administração & dosagem , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Quimioterapia de Indução , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Taxoides/administração & dosagem
4.
Ann Oncol ; 23(4): 1016-22, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21865152

RESUMO

BACKGROUND: The efficacy and safety of a novel combination of weekly paclitaxel and the epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab for the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck were investigated. PATIENTS AND METHODS: Patients received paclitaxel (80 mg/m(2)) and cetuximab (400/250 mg/m(2)), weekly, until disease progression or unacceptable toxicity. The primary end point was response rate. RESULTS: Among 46 patients enrolled, the overall response rate was 54% [95% confidence interval (CI) 39% to 69%], with 10 (22%) complete responses and a disease control rate of 80%. Median progression-free and overall survival times were 4.2 (95% CI 2.9-5.5 months) and 8.1 months (95% CI 6.6-9.6 months), respectively. Common grade 3/4 adverse events were acne-like rash (24%), asthenia (17%) and neutropenia (13%). Prior chemotherapy and the development of acne-like rash were associated with tumor response but not survival. No association between tumor EGFR expression or EGFR gene copy number and response or survival was found. CONCLUSION: The combination of cetuximab and weekly paclitaxel was active and well tolerated by these poor prognosis patients and may be an option for the treatment of medically unfit patients, particularly those for whom platinum is contraindicated.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/secundário , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Cetuximab , Receptores ErbB/metabolismo , Exantema/induzido quimicamente , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Paclitaxel/administração & dosagem , Resultado do Tratamento
5.
Clin Transl Oncol ; 23(4): 764-772, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32797376

RESUMO

BACKGROUND: Our previous phase-3 study (TTCC 2503) failed to show overall survival advantage of 2 induction chemotherapy (IC) regimens followed by standard concurrent chemoradiotherapy (CRT) over CRT alone in patients with unresectable locally advanced head and neck squamous-cell carcinoma (LAHNSCC). This study described the long-term survival of those patients. MATERIALS AND METHODS: Long-term follow-up study of patients with untreated LAHNSCC assigned to IC (three cycles), with either docetaxel, cisplatin and 5-fluorouracil (TPF arm) or cisplatin and 5-fluorouracil (PF arm), followed by CRT, or CRT alone, included in the previous TTCC 2503 trial. RESULTS: In the intention-to-treat population (n = 439), the median OS times were 25.4 (95% CI, 16.8-34.4), 26.2 (95% CI, 18.2-36.6) and 25.4 months (95% CI, 17.4-36.0) in the TPF-CRT, PF-CRT and CRT arms, respectively (log-rank p = 0.51). In the per-protocol population (n = 355), patients with larynx-hypopharynx primary tumors treated with IC (TPF or PF) followed by CRT had a longer median PFS than those who received CRT alone. Moreover, patients with ECOG 0 treated with IC (TPF or PF) followed by CRT had a better TTF than those with CRT alone. There were no statistically significant differences in terms of OS, PFS or TTF, according to the tumor load or affected nodes. CONCLUSION: After a long follow-up, the TTCC 2503 trial failed to show the benefit of IC-CRT in unresectable LAHNSCC regarding the primary end point. However, fit patients with ECOG 0 and primary larynx-hypopharyngeal tumors may benefit from the use of IC if administered by an experienced team. ClinicalTrials.gov identifier NCT00261703.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Neoplasias de Cabeça e Pescoço/mortalidade , Quimioterapia de Indução , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Cisplatino/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Intervalos de Confiança , Docetaxel/uso terapêutico , Fluoruracila/uso terapêutico , Seguimentos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Neoplasias Hipofaríngeas/tratamento farmacológico , Neoplasias Hipofaríngeas/mortalidade , Neoplasias Hipofaríngeas/patologia , Neoplasias Hipofaríngeas/terapia , Análise de Intenção de Tratamento , Neoplasias Laríngeas/tratamento farmacológico , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/terapia , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Neoplasias Bucais/terapia , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , 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/terapia , Taxoides/uso terapêutico , Resultado do Tratamento , Carga Tumoral
6.
Clin Transl Oncol ; 9(3): 172-6, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17403628

RESUMO

Intramedullary spinal cord metastases (ISCM) are uncommon and present with rapidly progressing neurological deficits. The objective of this study was to determine the rate, duration of neurological response and survival after radiation therapy. We have retrospectively reviewed the clinical outcome of six cases with a diagnosis of ISCM from primary lung cancer, non-small cell (NSCLC) (n=3) and small cell (SCLC) (n=3). Total radiation dose ranged from 27 Gy/5 fr to 40 Gy/20 fr. Ambulation was preserved in 3 patients and partially recovered in one. Five out of the six patients (83%) showed improvement in neurological signs/symptoms with a mean duration of 17.2 days (max: 40 days; min: 6 days). Median survival time was 5 months (confidence interval (CI) 95%: 0-12) for NSCLC and 5 months (CI 95%: 4-6) for SCLC. Although radiation response rate is high, the interval free of neurological progression is very short. A therapeutic approach should be considered for each individual.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/secundário , Carcinoma de Células Pequenas/secundário , Neoplasias Pulmonares/patologia , Neoplasias da Medula Espinal/secundário , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/radioterapia , Vértebras Cervicais , Intervalo Livre de Doença , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Paraplegia/etiologia , Dosagem Radioterapêutica , Estudos Retrospectivos , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/radioterapia , Neoplasias da Medula Espinal/complicações , Neoplasias da Medula Espinal/radioterapia , Vértebras Torácicas , Resultado do Tratamento
7.
J Clin Oncol ; 14(7): 2091-7, 1996 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8683241

RESUMO

PURPOSE: Circulating melanoma cells can be detected in peripheral blood by means of tyrosinase mRNA amplification by reverse-transcriptase polymerase chain reaction (RT-PCR). We conducted a prospective study to evaluate the clinical significance of the presence of circulating neoplastic cells in the blood of patients with malignant melanoma (MM). METHODS: A sensitive RT-PCR assay was used to detect tyrosinase mRNA in the peripheral blood of patients with stages I to IV melanoma. Healthy subjects or patients with other malignancies were used as negative controls. RESULTS: Ninety-one assessable patients were included in the study. There was a statistically significant association between RT-PCR positivity and clinical stage. Circulating melanoma cells were detected in 36% of patients with localized disease (stages I and II), in 45% of patients with regional nodal involvement (stage III), and in 94% of patients with metastatic disease (stage IV) (P < .001). In stage II-III patients who were RT-PCR-positive for mRNA tyrosinase in blood, the recurrence rate and disease-free survival were significantly worse than patients who were RT-PCR-negative. In multivariate analysis, RT-PCR was an independent prognostic factor for recurrence in patients with nonmetastatic disease (P = .002). CONCLUSION: The detection of circulating melanoma cells in peripheral blood by RT-PCR correlated with the clinical stage of patients with melanoma and was an independent prognostic factor for recurrence. Further studies are warranted to better assess the significance of this test in the evaluation of prognosis, early detection of relapse, and in monitoring the effectiveness of systemic therapy.


Assuntos
Melanoma/sangue , Células Neoplásicas Circulantes , Reação em Cadeia da Polimerase , Neoplasias Cutâneas/sangue , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Melanoma/mortalidade , Melanoma/patologia , Melanoma/secundário , Pessoa de Meia-Idade , Estudos Prospectivos , DNA Polimerase Dirigida por RNA , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia
8.
J Clin Oncol ; 16(3): 1036-9, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9508188

RESUMO

PURPOSE: We performed a clinical trial to determine whether postoperative adjuvant chemotherapy with two drugs versus one drug could prolong survival. PATIENTS AND METHODS: From 1985 to 1996, 85 patients with completely resected locally advanced gastric cancer were enrolled. The subjects were randomized into two treatment groups, as follows: mitomycin (MMC) 10 to 20 mg/m2 intravenously (i.v.) on day 1 every 6 weeks plus ftorafur (FT) 500 mg/m2/d for 36 consecutive days; or MMC alone, 10 to 20 mg/m2 i.v. every 6 weeks. All courses were repeated four times. RESULTS: After a median follow-up duration of 62 months, the overall 5-year survival rates were 67% for the MMC-FT group versus 44% for the MMC group (P = .04). Subgroup analysis to compare survival curves using the method of Mantel-Cox showed survival rates significantly in favor of the MMC-FT group in the subsets of patients with node-negative disease (P = .01) and those whose disease was stage IB or II (P = .008). CONCLUSION: Significantly better survival results were observed for MMC-FT versus MMC alone. Subset analysis suggest a strong benefit in patients with node-negative and early-stage resected gastric cancer.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antibióticos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mitomicinas/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/cirurgia , Adulto , Idoso , Quimioterapia Adjuvante , Feminino , Gastrectomia , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Mitomicinas/administração & dosagem , Esplenectomia , Neoplasias Gástricas/cirurgia , Análise de Sobrevida , Tegafur/administração & dosagem
9.
Eur J Cancer ; 29A(3): 340-2, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8398330

RESUMO

In order to evaluate the results on successful adjuvant chemotherapy in resected gastric cancer we performed a randomised trial on 134 patients in two arms: a control one with no further treatment after surgery versus a treatment arm given mitomycin-C (MMC), 20 mg/m2 intravenously one day every 6 weeks for four courses, starting before the sixth week after surgery. The median follow-up was 105 months. In the control arm, 49 out of 66 patients died due to recurrence, versus 40 out of 68 patients in treatment arm. Actuarial survival curve was statistically significant (P < 0.025) in favour of the treatment group. Liver metastases were lower in adjuvant group than in the control group (8/68 versus 19/66). Toxicity was mild. Main toxic effects were thrombocytopenia, leukopenia, nausea and vomiting. A pelvis renal cancer as a second malignancy 8 years after gastric cancer was observed. In that particular case MMC was given after surgery. We conclude that adjuvant chemotherapy based on MMC given in the early period after surgery, improves survival rate in gastric cancer resected patients.


Assuntos
Mitomicina/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Humanos , Leucopenia/induzido quimicamente , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Mitomicina/efeitos adversos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Trombocitopenia/induzido quimicamente
10.
Eur J Cancer ; 28A(4-5): 835-7, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1326308

RESUMO

25 consecutive inoperable or extended non-small cell lung cancer (NSCLC) patients (19 non-chemotherapy pretreated, 6 non-heavily pretreated) were given oral etoposide, 50 mg/m2/day for 21 successive days, every 4 weeks. 5 partial responses (PR), 9 disease stabilizations were achieved; the overall response rate of 20% (95% confidence interval, 4% to 36%) or 26% in non-pretreated patients. Median survival and PR duration probabilities were 6.7 months and 6.3 months, respectively. Alopecia excepted (96% of patients), non-haematological toxicity was mild. Haematological toxicity WHO grade II+III mainly consisted of leukopenia (28%).


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Etoposídeo/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Administração Oral , Adulto , Idoso , Esquema de Medicação , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
Cancer Chemother Pharmacol ; 33(6): 527-9, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-8137464

RESUMO

Chronic oral etoposide has shown activity in some metastatic refractory tumors. To test its activity in previously treated metastatic breast cancer patients, we started a study in 18 consecutive patients given etoposide orally at 50 mg/m2 daily for 21 days. A partial response was observed in 4 of 18 patients (22%); of the responding patients, 3 had visceral metastases and 1 had multiple bone metastases. Leukopenia of grade 3 or 4 was the main hematological toxic effect (23% of patients) and alopecia was the most important nonhematological toxicity. Chronic oral etoposide shows some activity in pretreated patients with metastatic breast cancer, with tolerance being good and toxicity, acceptable. Further studies of this drug given as first-line chemotherapy or in combination with other drugs can establish all its potential activity in this cancer.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Etoposídeo/uso terapêutico , Administração Oral , Adulto , Idoso , Neoplasias da Mama/patologia , Esquema de Medicação , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade
12.
Anticancer Res ; 14(2B): 705-8, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-8010730

RESUMO

We have measured serum CEA levels in 207 patients with colorectal cancer. CEA sensitivity was related to tumor stage in tumors located in the right colon, but not in tumors located in the left colon or the rectum. CEA had prognostic value in patients with tumors located in the right colon (p < 0.001) but not in the left colon or the rectum. However, CEA did not have prognostic value independent of Dukes stage even in tumors in the right colon. Our results underline the different sensitivities and prognostic values for primary tumors in the left and right colorectal regions.


Assuntos
Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/sangue , Neoplasias do Colo/sangue , Neoplasias do Colo/patologia , Neoplasias Colorretais/patologia , Seguimentos , Humanos , Ensaio Imunorradiométrico , Estadiamento de Neoplasias , Prognóstico , Neoplasias Retais/sangue , Neoplasias Retais/patologia , Análise de Sobrevida , Fatores de Tempo
13.
Anticancer Res ; 18(1B): 631-4, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9584045

RESUMO

BACKGROUND: The significance of tumor markers in lung cancer is not well established. PATIENTS AND METHODS: We analyzed level of serum markers as prognostic factor of response and survival in 46 evaluable patients with locally advanced or metastasic non small cell lung cancer. All patients were treated with cisplatin 120 mg/m2 or carboplatin 400 mg/m2 day 1, plus etoposide 80 mg/m2 days 1 to 3. RESULTS: Partial response was obtained in 11 patients (24%), stabilization in 18 and progression in 17. Tumor marker sensitivities were: CEA 37%, CA 125 54.5%, SCC 17.5%, NSE 30.5%, and CYFRA 52%. Higher levels of CEA and NSE correlated with more probability of response (p < 0.001 and p = 0.002). The survival probability of patients with normal pretreatment levels of NSE was significantly better than those with NSE over normal level (15.2 vs 7.2 months) p = 0.02. In patients who achieved partial response, CEA, CA 125 and CYFRA levels decreased significantly with respect to the pretreatment values. CONCLUSIONS: Patients with high CEA and NSE serum level have an increased probability of response than patients with low initial levels; however, patients with high initial level of NSE have poor survival. The decrease in CEA, CA 125 and CYFRA values at the moment of response evaluation could help in response assessment.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Cisplatino/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Resultado do Tratamento
14.
Int J Biol Markers ; 8(2): 113-23, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8366294

RESUMO

Mucin-like Carcinoma-associated Antigen (MCA) has been associated with many breast cancers. The aim of this study was to evaluate MCA in tumor tissue and serum as a potential tumor marker for prognosis and disease monitoring. MCA levels were determined in the tissue of 196 patients with primary breast cancer, 25 with metastatic disease and 25 patients with benign diseases, in pellet and/or cytosol. MCA levels were also determined in the serum of 50 patients with benign diseases, 148 with primary breast cancer (Mo), 150 with metastatic breast cancer (MT), and 200 with no clinical evidence of disease (NED). MCA tissue concentrations in pellet and cytosol were similar: 66.7 + 251 U/mg and 41.1 + 53 U/mg, respectively. No relationship between MCA levels and tumor size or nodal involvement was found. Higher MCA levels were observed in patients with ER+ or PgR+ tumors than in those with ER- or PgR- tumors (p < 0.01). Patients with MCA pellet concentrations lower than 10 U/mg of protein had shorter disease-free intervals (DFI) than those with higher values (p < 0.05). Abnormally high serum levels of MCA were found in 8% of patients with benign diseases, 4% of NED patients, 22% of Mo patients, and in 76% of MT cases. In primary breast cancer MCA values were related to tumor size and nodal involvement. A trend toward a lower DFI in patients with elevated presurgical MCA levels was observed but was of no statistical significance. These differences became statistically significant when patients were subdivided according to nodal status, with shorter DFI in those without nodal invasion (p < 0.05). In metastatic patients, changes in serum MCA were related to the tumor's response to treatment in 82% of cases. The highest MCA values were found in patients with liver or bone metastasis and the lowest values were found in those with locoregional recurrence. In conclusion, although MCA is not a specific tumor marker, it can be useful as a prognostic factor (tissue and serum) and in monitoring metastatic patients.


Assuntos
Antígenos de Neoplasias/metabolismo , Antígenos Glicosídicos Associados a Tumores , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/imunologia , Adenofibroma/imunologia , Adenofibroma/metabolismo , Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/imunologia , Neoplasias da Mama/metabolismo , Carcinoma/imunologia , Carcinoma/metabolismo , Carcinoma/secundário , Estudos de Avaliação como Assunto , Feminino , Doença da Mama Fibrocística/imunologia , Doença da Mama Fibrocística/metabolismo , Humanos , Metástase Linfática/imunologia , Prognóstico , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo
15.
Am J Clin Oncol ; 15(2): 160-2, 1992 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-1553906

RESUMO

Twenty-seven metastatic breast adenocarcinoma patients, pretreated with standard hormonotherapy or chemotherapy, received carboplatin 100 mg/m2/day x 3 intravenously (i.v.) plus etoposide 100 mg/m2/d x 3 i.v. repeated at 4-week intervals. There were five partial responses (18.5%), two minor responses, and 12 disease stabilizations. The dominant metastatic disease sites were soft tissue in three partially responding patients and visceral metastases in the two remaining responders. The median duration of response and time to progression were, respectively, 10 and 26 weeks. Major toxicity was myelosuppression with 85% of patients developing leukopenia; 48%, anemia; and 30%, thrombocytopenia. Carboplatin plus etoposide has shown antitumor activity in our group of pretreated patients. Based on the same schedule, a first-line carboplatin plus etoposide Phase II trial has been started.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adenocarcinoma/secundário , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Carboplatina/administração & dosagem , Avaliação de Medicamentos , Etoposídeo/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade
16.
Am J Clin Oncol ; 13(2): 98-100, 1990 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2316488

RESUMO

Sixteen patients with hepatic metastases of histologically documented breast cancer were treated with etoposide (VP 16-213) and cyclophosphamide. Previously, 6 had shown relapse in the liver after adjuvant chemotherapy, 2 had failed to respond to another chemotherapy combination, and 8 had never undergone chemotherapy. Fifty percent responded to treatment, including 1 complete remission and 7 partial responses. Median survival was 16 months and median duration of response was 13 months. All patients showed alopecia and moderate leukopenia; 13 experienced moderate gastrointestinal toxicity; there was 1 mild case of anemia and 1 case of moderate hemorrhagic cystitis. This study suggests that the combination of VP 16-213 and cyclophosphamide is a well-tolerated and effective treatment in advanced breast cancer patients with liver metastases.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Administração Oral , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Sinergismo Farmacológico , Etoposídeo/administração & dosagem , Feminino , Humanos , Injeções Intravenosas , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , Indução de Remissão
17.
Am J Clin Oncol ; 17(2): 134-6, 1994 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7511327

RESUMO

Forty consecutive patients with local advanced cancer of the oral cavity and lip, heavily pretreated, were palliated with two courses of carboplatin, 400 mg/m2 intravenously once a month plus ftorafur, 500 mg/m2 daily per os for 30 days. Previous treatment consisted of surgery (17 patients), radiation therapy (23 patients), and chemotherapy with cisplatin plus bleomycin (15 patients). The main sites of primary tumor were the tongue (12 patients), hard palate (6 patients), retromolar area (6 patients), tonsils (6 patients), perioral skin and lip (5 patients), and floor of the mouth (5 patients). Complete response was observed in 3 patients, and partial response in 7. Symptomatic improvement was observed in 56% of the cases. Median duration of response was 9 months. Median survival was 7 months. The main toxic effects were nausea (39 cases), vomiting (35 cases), and thrombocytopenia (4 cases). We conclude that carboplatin plus ftorafur has a role as palliative chemotherapy in cancer of the oral cavity and lip in heavily pretreated patients when local therapies are not suitable.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Labiais/tratamento farmacológico , Neoplasias Bucais/tratamento farmacológico , Cuidados Paliativos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Neoplasias Labiais/mortalidade , Neoplasias Labiais/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Estadiamento de Neoplasias , Taxa de Sobrevida , Tegafur/administração & dosagem , Resultado do Tratamento
18.
Tumori ; 82(3): 221-4, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8693597

RESUMO

AIMS AND BACKGROUND: The purpose of this study was to retrospectively compare different approaches including neoadjuvant chemotherapy. METHODS: Ninety-six consecutive patients with pyriform sinus squamous cell carcinoma with no distant metastases were entered. The first 48 patients were treated with surgery plus postoperative radiation therapy (50-60 Gy) over cervical lymphatics. The next 48 patients were treated by induction chemotherapy with two courses of cisplatin, 120 mg/m2 i.v. day one, plus bleomycin, 20 mg/m2/day for 5 consecutive days in 24-hr i.v. perfusion followed by definitive surgery and postoperative radiation therapy as in the first therapeutic group. RESULTS: Definitive surgery was performed in 38 control vs 39 neoadjuvant patients. Complete response was observed in 9 (18.7%) and partial response in 32 (66.7%) of 48 chemotherapy-treated patients. Partial plus complete response was seen in 41 (85.4%) of the 48 patients. Comparison between controls versus chemotherapy-treated groups showed persistence of the disease in 10 vs 9 patients; local-regional relapses in 21 versus 14 patients; and distant metastases in 4 vs 2 patients. Median survival was 12 vs 40 months. Survival curves were statistically better in neoadjuvants than in controls (P < 0.025). CONCLUSIONS: Multidisciplinary therapy slightly decreases the rate of local-regional relapses and distant metastases and should improve survival in this set of pyriform sinus cancer patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Faríngeas/tratamento farmacológico , Adulto , Idoso , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Carcinoma de Células Escamosas/mortalidade , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Faríngeas/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida
19.
Int Surg ; 83(1): 8-10, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9706507

RESUMO

BACKGROUND: Resective surgery can play a role in solitary pulmonary metastasis or in a few multiple metastases of the lungs. METHODS: We performed a retrospective analysis of the cure rate and survival in patients with pulmonary metastases after surgical resection. Inclusion criteria included no evidence of extrapulmonary metastases or local control of the primary neoplasia. Selective adjunctive therapy was added when applicable. RESULTS: Twenty-five out of 53 patients with resected pulmonary metastases are still alive and disease free. After a 5-year period of follow-up the cure rate obtained was 42%. CONCLUSIONS: In selected patients, resective surgery of solitary or limited multiple pulmonary metastases should be useful, offering the patients a high rate of curability and long term survival. These positive results suggest that adjunctive therapies should be added after resective surgery.


Assuntos
Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Humanos , Neoplasias Pulmonares/mortalidade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
20.
Clin Transl Oncol ; 15(12): 1025-9, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23982852

RESUMO

Nasopharyngeal carcinoma cases are not frequently encountered in our environment. Local stages are treated with radiotherapy. For advanced local stages, the association of chemotherapy with radiotherapy improves the rates of survival. In the case of metastatic disease stages, treatment requires platinum-based chemotherapy and patients may achieve a long survival time.


Assuntos
Neoplasias Nasofaríngeas/terapia , Algoritmos , Carcinoma , Humanos , Monitorização Fisiológica/normas , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/patologia , Metástase Neoplásica , Estadiamento de Neoplasias/normas , Recidiva
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