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1.
Sci Rep ; 13(1): 12255, 2023 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-37507480

RESUMO

Nowadays, treatment of metastatic breast cancer (MBC) has been enriched with novel therapeutical strategies. Metronomic chemotherapy (mCHT) is a continuous and frequent administration of chemotherapy at a lower dose and so whit less toxicity. Thus, this strategy could be attractive for elderly MBC patients. Aim of this analysis is to provide insights into mCHT's activity in a real-life setting of elderly MBC patients. Data of patients ≥ 75 years old included in VICTOR-6 study were analyzed. VICTOR-6 is a multicentre, Italian, retrospective study, which collected data on mCHT in MBC patients treated between 2011 and 2016. A total of 112 patients were included. At the beginning of mCHT, median age was 81 years (75-98) and in 33% of the patients mCHT was the first line choice. Overall Response Rate (ORR) and Disease Control Rate (DCR) were 27.9% and 79.3%, respectively. Median PFS ranged between 7.6 and 9.1 months, OS between 14.1 and 18.5 months. The most relevant toxicity was the hematological one (24.1%); severe toxicity (grade 3-4) ranged from 0.9% for skin toxicity up to 8% for hematologic one. This is a large study about mCHT in elderly MBC patients, providing insights to be further investigated in this subgroup of frail patients.


Assuntos
Neoplasias da Mama , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Administração Metronômica , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Estudos Retrospectivos
2.
Breast Cancer Res Treat ; 190(3): 415-424, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34546500

RESUMO

PURPOSE: Triple-negative breast cancer (TNBC) represents a subtype of breast cancer which lacks the expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2): TNBC accounts for approximately 20% of newly diagnosed breast cancers and is associated with younger age at diagnosis, greater recurrence risk and shorter survival time. Therapeutic options are very scarce. Aim of the present analysis is to provide further insights into the clinical activity of metronomic chemotherapy (mCHT), in a real-life setting. METHODS: We used data included in the VICTOR-6 study for the present analysis. VICTOR-6 is an Italian multicentre retrospective cohort study, which collected data of metastatic breast cancer (MBC) patients who have received mCHT between 2011 and 2016. Amongst the 584 patients included in the study, 97 were triple negative. In 40.2% of the TNBC patients, mCHT was the first chemotherapy treatment, whereas 32.9% had received 2 or more lines of treatment for the metastatic disease. 45.4% out of 97 TNBC patients received a vinorelbine (VRL)-based regimen, which resulted in the most used type of mCHT, followed by cyclophosphamide (CTX)-based regimens (30.9%) and capecitabine (CAPE)-based combinations (22.7%). RESULTS: Overall response rate (ORR) and disease control rate (DCR) were 17.5% and 64.9%, respectively. Median progression free survival (PFS) and overall survival (OS) were 6.0 months (95% CI: 4.9-7.2) and 12.1 months (95% CI: 9.6-16.7). Median PFS was 6.9 months for CAPE-based regimens (95% CI: 5.0-18.4), 6.1 months (95% CI: 4.0-8.9) for CTX-based and 5.3 months (95% CI: 4.1-9.5) for VRL-based ones. Median OS was 18.2 months (95% CI: 9.1-NE) for CAPE-based regimens and 11.8 months for VRL- (95% CI: 9.3-16.7 and CTX-based ones (95%CI: 8.7-52.8). Tumour response, PFS and OS decreased proportionally in later lines. CONCLUSION: This analysis represents the largest series of TNBC patients treated with mCHT in a real-life setting and provides further insights into the advantages of using this strategy even in this poor prognosis subpopulation.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Capecitabina/uso terapêutico , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Receptor ErbB-2/genética , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
3.
Breast ; 48: 7-16, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31470257

RESUMO

Metronomic chemotherapy (mCHT) refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen, with no prolonged drug-free breaks, that leads to antitumor activity. Aim of the present study is to describe the use of mCHT in a retrospective cohort of metastatic breast cancer (MBC) patients in order to collect data regarding the different types and regimens of drugs employed, their efficacy and safety. Between January 2011 and December 2016, data of 584 metastatic breast cancer patients treated with mCHT were collected. The use of VRL-based regimens increased during the time of observation (2011: 16.8% - 2016: 29.8%), as well as CTX-based ones (2011: 17.1% - 2016: 25.6%), whereas CAPE-based and MTX-based regimens remained stable. In the 1st-line setting, the highest ORR and DCR were observed for VRL-based regimens (single agent: 44% and 88%; combination: 36.7% and 82.4%, respectively). Assuming VRL-single agent as the referee treatment (median PFS: 7.2 months, 95% CI: 5.3-10.3), the longest median PFS were observed in VRL-combination regimens (9.5, 95%CI 88.8-11.3, HR = 0.72) and in CAPE-single agent (10.7, 95%CI 8.3-15.8, HR = 0.70). The VICTOR-6 study provides new data coming from the real-life setting, by adding new information regarding the use of mCHT as an option of treatment for MBC patients.


Assuntos
Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
4.
Oncology ; 68(4-6): 438-45, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16020974

RESUMO

OBJECTIVES: We conducted a multicenter phase II study to evaluate the clinical efficacy, toxicity, and dose intensity of a new weekly schedule of docetaxel and gemcitabine as first-line treatment of metastatic breast cancer patients. METHODS: We enrolled 58 patients, 52% of whom had received a previous anthracycline-containing chemotherapy. The treatment schedule was: docetaxel 35 mg/m2 and gemcitabine 800 mg/m2 i.v. on days 1, 8, 15 every 28 days. RESULTS: All patients were assessable for toxicity and 56 for efficacy. Overall response rate was 64.3% with 16.1% of complete responses and 48.2% of partial responses. Median survival was 22.10 months (95% CI: 15.53-28.67) and median time to tumor progression was 13.6 months (95% CI: 10.71-16.49). The most common hematological toxicity was neutropenia (no febrile neutropenia), which occurred in 28 patients (48.3%) but grade 3-4 in only 8 patients (14%). Alopecia, the most common nonhematological toxicity, occurred in 20 (34.5%) patients, but only 5 patients (8.6%) experienced grade 3 alopecia. CONCLUSION: The activity of docetaxel and gemcitabine in metastatic breast cancer is confirmed. The promising results of the employed schedule, in agreement with other published studies, need to be further confirmed within a phase III study.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Lobular/tratamento farmacológico , Carcinoma Medular/tratamento farmacológico , Adulto , Idoso , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/secundário , Carcinoma Medular/secundário , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Docetaxel , Feminino , Humanos , Dose Máxima Tolerável , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida , Taxoides/administração & dosagem , Resultado do Tratamento , Gencitabina
5.
Oncology ; 63(3): 205-12, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12381898

RESUMO

OBJECTIVE: We conducted a multi-institutional phase II study to evaluate the tolerability and activity of a sequential schedule of treatment with doxorubicin and docetaxel in chemotherapy-naive women with advanced breast cancer. METHODS: A total of 73 patients with PS (ECOG) 0-2, aged <70 years and adequate bone marrow, renal, liver and cardiac functions were included in the study (13 stage III B and 60 stage IV). The schedule of administration was doxorubicin 50 mg/m2 by intravenous (i.v.) 30 min injection on day 1 followed the day after by docetaxel 75 mg/m2, by i.v. 60 min infusion. Cycles were repeated every 28 days. RESULTS: Overall, the median number of administered cycles was 6 (range 1-14). The most common toxicity was hematological, with 56.2% of the patients who experienced grade 3-4 neutropenia. However, febrile neutropenia occurred only in 2.8% of the cases. The median cumulative dose of doxorubicin was 350 mg/m2 (range 50-700 mg/m2). Eleven patients (15.4%) were documented to have >10% but <20% decrease in the left ventricular ejection fraction. No case of congestive heart failure was recorded. No patient experienced treatment-related death. Among the 68 evaluable patients, the overall objective response rate was 73.5% (95% confidence limits: 63-84%): 10 patients (14.7%) obtained a complete remission and 40 (58.8%) had a partial response. Only 10 patients (14.7%) experienced progressive disease. The median duration of response was 10 months (2-54+). CONCLUSION: This sequential treatment with doxorubicin and docetaxel is an effective, feasible and a well-tolerated regimen. The main toxicity was neutropenia. The lack of cardiotoxicity is an important advantage of such a doxorubicin-docetaxel combination and it justifies phase III comparative studies with other anthracyclines/taxanes containing schedules in both advanced and early-stage breast cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Paclitaxel/análogos & derivados , Taxoides , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Docetaxel , Doxorrubicina/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Taxa de Sobrevida , Resultado do Tratamento
6.
Ann N Y Acad Sci ; 963: 91-7, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12095933

RESUMO

Oxaliplatin is a platinum compound that inhibits DNA synthesis. This drug has a broad spectrum of antineoplastic activity, and its results in breast cancer are promising. We began a phase II study in pretreated advanced breast cancer patients using oxaliplatin together with 5-fluorouracil and folinic acid, a combination based on the efficacy of both drugs in breast cancer and their different toxicity profiles. Seventeen patients with advanced breast cancer were treated with oxaliplatin, 5-fluorouracil, and folinic acid, and preliminary data were analyzed. The mean number of courses per patient was 2.82 (range 1-8). The main toxicity was gastrointestinal, with nausea and vomiting G2-3 in 53% of the patients. Hematologic toxicity was moderate with neutropenia G2-3 in 13% of the patients. Among 10 evaluable patients we obtained partial response in one and stabilized the disease in two patients. No data on survival were evaluated. The small number of enrolled and evaluable patients does not permit any conclusions to be drawn. The study is ongoing.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Resultado do Tratamento
7.
Lung Cancer ; 34(1): 115-23, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11557121

RESUMO

A phase II study in patients with stage IIIB/IV non-small cell lung cancer (NSCLC) was carried out to evaluate the clinical activity and toxicity of the chemotherapeutic combination of gemcitabine+vinorelbine (GEM/VNR). Forty-five patients (40 male, 5 female) with a median age of 67 years (range 37-73) and a median ECOG performance status of 1 (range 0-2) were enrolled into the trial. Twenty patients had stage IIIB (two positive supraclavicular nodes and 20 cytologically positive pleural effusion), and 25 had stage IV NSCLC. GEM 1000 mg/m(2) diluted in 250 cc(3) of normal saline was administered iv on days 1, 8, and 15, while VNR was given 30 mg/m(2) on days 1 and 8 every 4 weeks. The median number of courses/patient was 4 (range 3-7). According to an intent-to-treat analysis 2 (4%) patients had a complete response and 16 (36%; 95% CL 22-52%) had a partial response for an overall response rate of 40% (95% CL 26-56%). Twelve (27%) patients had stable disease and 15 (33%) were considered as treatment failures. Median overall survival of the whole series was 8+ months with 33% of patients alive at 1 year. Toxicity was generally mild. WHO grade 3-4 neutropenia was recorded in 22% of cases, grade 1-3 liver toxicity in 6% of patients and neutropenia-unrelated fever in 9%. This multicentre phase II study suggests that the GEM/VNR combination regimen is an active and well tolerated regimen in patients with stage IIIB/IV NSCLC. Larger studies comparing cisplatin-based regimens to new schedules without cisplatin are warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Vimblastina/análogos & derivados , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Desoxicitidina/administração & dosagem , Feminino , Humanos , Infusões Intravenosas , Injeções Intravenosas , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Análise de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagem , Vinorelbina , Gencitabina
9.
Ann Oncol ; 11(4): 495-6, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10847474

RESUMO

PURPOSE: Gemcitabine (GEM) and vinorelbine (VNR) are both active against advanced breast cancer (ABC), being able to induce a median ORR of 25% and 40%, respectively. Because of their different mechanism of action and good tolerability, the combination of GEM and VNR has been tested in ABC. PATIENTS AND METHODS: Twenty-nine ABC patients pretreated with anthracycline-taxane were treated with GEM 1000 mg/m2 on day 1, 8, 15, and VNR 25 mg/m2 on day 1 and 8 every twenty-eight days. Analysis of toxicity pattern, response rate, TTP and OS were carried out. RESULTS: Twenty-nine patients were enrolled into the trial. The ORR was 48% (95% CI: 29-67): a CR was observed in three patients (10%; 95% CI: 2-27), while eleven patients (38%; 95 CI: 21-58) achieved PR, eight (28%) had a SD, and seven (24%) progressed. Toxicity was mainly hematological and included: grade 3 leukopenia in 48% of cases without episodes of neutropenic fever, grade 3-4 thrombocytopenia in 10%, and grade 2 anemia in 7%. Non-hematological toxicities were mild and rather infrequent. CONCLUSIONS: The GEM-VNR combination seems to be active in pretreated ABC with an acceptable toxicity pattern, and may well reppresent an interesting therapeutic choice after anthracycline/taxane regimens.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Projetos Piloto , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Vinorelbina , Gencitabina
10.
Haematologica ; 84(11): 1016-23, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10553163

RESUMO

BACKGROUND AND OBJECTIVE: Several in vitro and animal studies have shown that IL-3 primes hematopoietic stem cells to become more sensitive to later acting growth factors. We wanted to compare the toxicity and the synergistic stimulatory effect of interleukin-3 (IL-3) followed by granulocyte colony-stimulating factor (G-CFS) or granulocyte-macrophage colony-stimulating factor (GM-CSF) on white blood cell (WBC) and platelet counts, after standard-dose chemotherapy (CT) in patients with solid tumors. DESIGN AND METHODS: Fifty consecutive cancer patients with thrombocytopenia and/or leukopenia registered during a previous course of CT were randomized to receive, after the following course, IL-3 (10 microg/kg/day, s.c., day 1-5) followed by G- or GM-CSF (5 microg/kg/day, day 6-8). RESULTS: The nadir of WBC in the cycles supported with the combination of IL-3 and G-CSF was significantly higher than that observed in the CT cycles not supported by growth factors (p < 0. 005). Furthermore, severe leukopenia was abrogated in all the cycles supported with IL-3+G-CSF, while in the cycles without cytokines, this event was registered in 62.5% of the cases (p < 0.0005). Finally, the recovery of WBC was achieved a mean of 4 days earlier in the cycles supported with IL-3+G-CSF. As for thrombocytoprotection, no significant differences were evidenced, but severe thrombocytopenia was abrogated in all the cycles supported by IL-3+G-CSF (p < 0.05). Furthermore, platelet recovery after CT was achieved on average 3.5 days earlier in the IL-3+G-CSF group than in the previous cycles. The nadir of WBC count in the cycles supported by the combination of IL-3 and GM-CSF was significantly higher than that observed in the CT cycles not supported by growth factors (p < 0.005). Furthermore, severe leukopenia was abrogated in 40% of the cycles supported by IL-3+GM-CSF, while in the cycles without cytokines, this event was registered in 80% of the cases (p < 0.005). Finally, the recovery of WBC was achieved a mean of 3.5 days earlier in the cycles supported by IL-3+GM-CSF. As far as thrombocytoprotection is concerned, there were no significant differences in the nadir between the cycles supported by the association IL-3+GM-CSF and the cycles not supported by cytokines. However, severe thrombocytopenia was registered in 20% of the cycles not supported by growth factors but in only 10% of the cycles supported by IL-3+GM-CSF (p < 0.05). Furthermore, platelet recovery after CT was achieved on average 3 days earlier in the IL-3+GM-CSF group. The combination of IL-3 and G-CSF would appear to be more effective than the combination of IL-3 and GM-CSF in the control of both severe thrombocytopenia and leukopenia. Indeed, severe leukopenia was abrogated in all the cycles in arm A, but only in 40% of the cycles in arm B (p < 0.0005). Furthermore, considering a platelet count below 49


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Interleucina-3/administração & dosagem , Neoplasias/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Feminino , Fator Estimulador de Colônias de Granulócitos/toxicidade , Fator Estimulador de Colônias de Granulócitos e Macrófagos/toxicidade , Humanos , Interleucina-3/toxicidade , Contagem de Leucócitos/efeitos dos fármacos , Leucopenia/induzido quimicamente , Leucopenia/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas/efeitos dos fármacos , Estudos Prospectivos , Trombocitopenia/induzido quimicamente , Trombocitopenia/tratamento farmacológico , Resultado do Tratamento
11.
Oncol Rep ; 5(6): 1459-64, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9769388

RESUMO

We enrolled 19 cancer patients (11 females, 8 males) with thrombocytopenia after standard dose of chemotherapy to receive IL3 10 mg/kg/day s.c. until hematologic recovery. Therapeutic success was obtained in 69.6% of cycles; a major response in 39.3% and a minor response in 30.3% of cycles. We obtained the best results in case of platelet count <49,000/mm3. The main toxicity was a flu-like syndrome. In two cycles (6%) we registered allergic episodes with flushing and lipothymia. In the 47% of cycles evaluable for toxicity no side effect was registered.


Assuntos
Antineoplásicos/efeitos adversos , Interleucina-3/uso terapêutico , Neoplasias/tratamento farmacológico , Trombocitopenia/terapia , Adulto , Idoso , Hipersensibilidade a Drogas , Feminino , Humanos , Interleucina-3/efeitos adversos , Masculino , Pessoa de Meia-Idade , Trombocitopenia/induzido quimicamente
12.
Pathol Res Pract ; 194(5): 319-24, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9651944

RESUMO

We studied a consecutive series of 54 cases of lower lip squamous cell carcinoma (LLSCC) in order to identify any variables which might predict the development of lymph node metastases. The cases were divided into 38 tumors without metastases (group I) and 16 tumors with lymph node metastases (group II). The following factors were investigated: tumor size, histologic grading maximal thickness, perineural invasion, DNA ploidy and PCNA expression. In conclusion, we found that LLSCC greater than 2 cm in diameter, with histological grading G3-G4, thickness of more than 6 mm, DNA aneuploidy and high PCNA expression (PCNA LI > 0.48), were at high risk for the development of lymph node metastases.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias Labiais/patologia , Distribuição por Idade , Idoso , DNA de Neoplasias/genética , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Ploidias , Prognóstico , Antígeno Nuclear de Célula em Proliferação/análise , Fatores de Risco , Distribuição por Sexo
13.
Oncol Rep ; 5(5): 1095-8, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9683815

RESUMO

We studied a consecutive series of 78 stage I cutaneous malignant melanoma in order to identify variables which might predict development of metastases. Anatomical site, sex, tumor thickness, Clark level, microscopic ulceration, growth phase, histologic type, cell type, and DNA ploidy were investigated. Lesions with tumor thickness 1.5 mm, Clark level IV-V, microscopic ulceration and DNA aneuploidy were at high risk for the development of metastases. This study showed the prognostic importance of DNA ploidy in stage I cutaneous malignant melanoma and the strong relationship between DNA ploidy and classic prognostic factors. This variable can be used in routine diagnosis for selecting a high-risk group of patients who may benefit from a more aggressive therapeutic approach.


Assuntos
Melanoma/genética , Melanoma/patologia , Ploidias , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Adulto , Idoso , Aneuploidia , Divisão Celular , Diploide , Feminino , Seguimentos , Humanos , Masculino , Melanoma/cirurgia , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Medição de Risco , Neoplasias Cutâneas/cirurgia , Fatores de Tempo
14.
Anticancer Res ; 18(2A): 911-4, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9615740

RESUMO

We studied a consecutive series of 54 cases of lower lip squamous cell carcinoma (LLSCC) in order to identify any variables which might predict the development of lymph node metastases. The cases were divided into 38 tumors without metastases (group I) and 16 tumors with lymph node metastases (group II). The following variables were investigated: tumor size, histologic grading, tumor maximal thickness, perineural infiltration and DNA ploidy, in a group of patients undergoing surgical treatment for LLSCC, and to show which of these might be predictive of the development of lymph node metastases.


Assuntos
Carcinoma de Células Escamosas/patologia , DNA de Neoplasias/análise , Neoplasias Labiais/patologia , Adulto , Idoso , Carcinoma de Células Escamosas/genética , Feminino , Humanos , Neoplasias Labiais/genética , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Ploidias
15.
J Cancer Res Clin Oncol ; 124(3-4): 191-8, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9619746

RESUMO

Biochemical modulation is one of the most interesting fields in cancer chemotherapy. Interferon-alpha (IFNalpha) is a cytokine that is able to influence the pharmacodynamics of 5-fluorouracil (5FU) through a number of mechanisms. With the aim of confirming some data emerging from the literature, we initiated a multicentric randomized study comparing the combination of 5FU and IFNalpha-2a with 5FU alone in the treatment of advanced or metastatic colon cancer. A group of 205 colon cancer patients (104 in the 5FU arm and 101 in the 5FU + IFNapha-2a arm) were included in the final intention-to-treat analysis. Rectal cancers were not considered eligible. All patients had measurable disease, were aged 75 years or less, had a Karnofsky index of at least 60 and had good bone marrow, renal, liver and cardiac functions. No previous chemo-immunotherapy was allowed. The treatment was 750 mg/m2 5FU (4 h i.v. infusion) on days 1 5 and then i.v. bolus weekly, starting from day 12, with or without IFNalpha-2a given s.c. three times weekly (starting dose 3 x 10(6) IU rising to 9 x 10(6) IU, if tolerated). Patients were treated until progression or, if responsive, for a maximum of 48 weeks and then observed for a period of 2 years. The primary end-point of the study was objective clinical response (OR); secondary parameters were time to progression, overall survival, and time to death after progression. WHO criteria were used for both clinical response and toxicity measurements. Dose reduction was planned a priori in the event of significant toxicity due to 5FU, IFNalpha-2a or both. Association between primary and secondary end-points and treatment was studied by univariate and multivariate analysis. Altogether, 47 patients achieved a documented response. A 25% OR was observed in the combination arm while a 21% OR was seen in the 5FU arm; this difference is not statistically significant (P = 0.6). Patients with a small tumour burden (below 5 cm2) showed a higher probability of response in both arms. Patients in the experimental arm had a higher but not statistically significant cumulative progression-free probability. Median survival was 47.1 weeks overall, while it was 43.7 and 48.5 weeks in the control and experimental arms, respectively. The combination was clearly more toxic than 5FU alone, leukopenia being the most frequent side-effect in the experimental arm and nausea and vomiting in the control arm. In conclusion these results are quite disappointing and 5FU + IFNalpha-2a can not be considered a standard treatment for advanced colon cancer.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Fluoruracila/uso terapêutico , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes
16.
Gynecol Oncol ; 68(2): 172-7, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9514802

RESUMO

Because of the relative lack of overlapping toxicity, carboplatin (PPL) and cisplatin (CDDP) can be easily combined for treatment of ovarian cancer to increase total platinum dose intensity. Ifosfamide (IFO), one of the most effective single agents in ovarian cancer, has a low hematological toxicity when administered in continuous infusion. From January 1991 to December 1993, 34 patients with advanced ovarian cancer, previously untreated with chemo- or radiotherapy, were enrolled in a phase I-II study with the aim of determining the maximum tolerated dose (MTD) of CDDP (on day 8 of a 28-day cycle) in combination with PPL (300 mg/m2 on day 1) and IFO (4,000 mg/m2/24 h by continuous infusion on day 1). The initial dose level of CDDP was 40 mg/m2, which was continuously increased by 10 mg/m2 up to the MTD defined as one dose level below that inducing dose-limiting toxicity (DLT) in at least two-thirds of treated patients; no dose escalation was allowed in the same patient. Grade 3-4 leukopenia and thrombocytopenia were observed in 54 and 49% of patients, respectively. The DLT was reached at 70 mg/m2 and therefore the dose recommended for the phase II study was 60 mg/m2. Complete (CR) plus partial response was observed in 88% of patients with a 21% pathological CR. With a minimum follow-up of 32 months (median 40 months), median progression-free survival and overall survival were 21 and 39 months, respectively. In conclusion, the combination of CDDP, PPL, and IFO provides an effective regimen for ovarian cancer with an acceptable toxicity profile.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Antineoplásicos Alquilantes/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Cisplatino/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Ifosfamida/administração & dosagem , Leucopenia/induzido quimicamente , Pessoa de Meia-Idade , Análise de Sobrevida , Trombocitopenia/induzido quimicamente , Resultado do Tratamento
18.
Oncol Rep ; 4(4): 723-7, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-21590128

RESUMO

We enrolled 11 consecutive pre-treated resistant advanced cancer patients to receive hydroxyurea (HU) (as modulator of MDR) 10 mg/kg/day (d) p.o. d 1-14 in association with DXR (d 15) alone or in combination with VDS (d 15) or VP16 (d 15-17) in presence, respectively, of soft tissue sarcoma, breast carcinoma, lung and gastric carcinoma. We obtained a stabilization of disease (NC) in 62.5% of patients, with a mean duration of 6 months. The mean survival was 12.2+ months for NC and 6 months for progressive disease (PD). No severe or unexpected adverse events were reported over 34 cycles administered; the most frequently recorded side effects were haematological and gastrointestinal toxicity. It seems that at the dosage we used, HU is poorly active in overcoming MDR; further studies with larger number of patients and different dosage are needed.

19.
Ann Oncol ; 7(8): 821-6, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8922196

RESUMO

PURPOSE: To compare mitomycin C plus vindesine plus etoposide (MEV) vs. mitomycin C plus vindesine plus cisplatin (MVP) in the treatment of stage IV non-small-cell lung cancer. PATIENTS AND METHODS: 204 patients were entered in a phase III multicentre randomised trial from June 1990 to December 1994 and stratified according to the ECOG performance status (0-1 vs. 2). MVP was given in the following dosages: mitomycin C 8 mg/m2+vindesine 3 mg/m2+cisplatin 100 mg/m2 i.v. day 1 and vindesine 3 mg/m2 i.v. day 8 with cycles repeated every 4 weeks. MEV was given in the following dosages: mitomycin C 8 mg/m2+vindesine 3 mg/ m2 i.v. day 1 and etoposide 100 mg/m2 i.v. days 1 to 3 with cycles repeated every 3 weeks. For both treatments a maximum of 6 cycles was planned. Response and toxicity were evaluated according to WHO. Subjective responses were assessed by numerical scales. Analyses were made on the basis of intent to treat. RESULTS: The objective response rate was 21.4% (1 CR + 21 PR among 103 patients) in the MEV and 28.7% (1 CR + 28 PR among 101 patients) in the MVP arm (P = 0.48). Symptoms were similar in the two arms. 196 patients progressed and 182 died. The median times to progression were 10 weeks (95% CI 9-12) and 12 weeks (95% CI 10-15) and median survivals were 29 weeks (95% CI 25-36) and 28 weeks (95% CI 25-35) in the MEV and MVP arms, respectively. The relative risks of progressing and of dying were 0.89 (95% CL 0.66-1.20) and 0.96 (95% CL 0.71-1.30), respectively, for patients receiving MVP as compared with those receiving MEV at multivariate analysis adjusted by sex, age, histologic type, number of metastatic sites, performance status at entry, and centre. CONCLUSIONS: In the present study, no significant differences were observed in response rate, survival or palliation of symptoms between the MEV and MVP regimens, while toxicity was significantly more frequent and severe with MVP. Thus, MEV should be considered a reasonable alternative to the MVP regimen in the treatment of stage IV NSCLC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Antibióticos Antineoplásicos/administração & dosagem , Antineoplásicos/administração & dosagem , Antineoplásicos Fitogênicos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Etoposídeo/administração & dosagem , Feminino , Humanos , Infusões Intravenosas , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Análise Multivariada , Taxa de Sobrevida , Resultado do Tratamento , Vindesina/administração & dosagem
20.
Ann Ital Chir ; 67(1): 27-33; discussion 34, 1996.
Artigo em Italiano | MEDLINE | ID: mdl-8712614

RESUMO

The authors, after illustrating physiopathologic aspects of gastric MALTomas, examine the H.P. infections and the possible relations between this kind of bacterium and gastric MALTomas. They hypothesize that H.P. infection represents an important predisposition to gastric lymphoma, due to anatomopathological modifications over gastric mucosa. They conclude that a decreasing of gastric lymphoma could be correlatable an opportune eradication of H.P. despite of at moment it's impossible hypothesize a marked decreasing of lymphoma by an eradication of H.P.


Assuntos
Infecções por Helicobacter/complicações , Helicobacter pylori , Linfoma de Zona Marginal Tipo Células B/etiologia , Neoplasias Gástricas/etiologia , Idoso , Amoxicilina/administração & dosagem , Antiulcerosos/administração & dosagem , Quimioterapia Combinada , Feminino , Gastrectomia , Infecções por Helicobacter/tratamento farmacológico , Humanos , Linfoma de Zona Marginal Tipo Células B/cirurgia , Masculino , Metronidazol/administração & dosagem , Pessoa de Meia-Idade , Omeprazol/administração & dosagem , Penicilinas/administração & dosagem , Neoplasias Gástricas/cirurgia
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