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2.
Ann Oncol ; 23(1): 135-141, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21531784

RESUMO

BACKGROUND: Previous studies investigating the prognostic role of mucinous histology of colorectal cancer produced conflicting results. This retrospective analysis was carried out in order to explore whether mucinous adenocarcinoma (MC) is associated with a comparatively worse prognosis than that of nonmucinous adenocarcinoma (NMC) for patients undergoing curative resection for stage II and III colon cancer. PATIENTS AND METHODS: This study involved 1025 unselected patients who underwent curative surgery for sporadic colon cancer and follow-up procedures at six different oncology departments. RESULTS: MCs accounted for 17.4% (n=178) of tumours. Patients with MC had 5- and 8-year overall survival rates of 78.6% and 68.8%, respectively, compared with 72.3% and 63.8%, respectively, for patients with nonmucinous tumours. Multivariate analysis using the Cox proportional hazards model showed that the clinically significant prognostic factors were stage of disease and adjuvant chemotherapy. No statistically significant interaction between mucinous histology and adjuvant chemotherapy was found. CONCLUSIONS: For patients with stage II and III colon cancer who underwent curative surgery, mucinous histology has no significant correlation with prognosis compared with NMC. This retrospective analysis suggests a comparable benefit from adjuvant chemotherapy for MC compared with NMC.


Assuntos
Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Adenocarcinoma Mucinoso/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Neoplasias do Colo/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos
3.
World J Oncol ; 2(5): 245-251, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29147255

RESUMO

BACKGROUND: Schedules with anthracyclines and taxanes are one of the best options for primary chemotherapy. The addition of trastuzumab showed an impressive percentage of pathological complete responses in Buzdar trial (66.7%). Recently, nonpegylated liposome-encapsulated doxorubicin (NLD) has been widely used in advanced breast cancer with high response rates (98.1 % in Cortes study). The aims of our study were to assess pathological responses and toxicity of NLD plus paclitaxel (and trastuzumab in patients with HER2 overexpression). METHODS: Thirty patients entered the study: 9 locally advanced and 21 operable. Median age was 58.5 years (range: 31-73). 23 patients without HER2 overexpression (or FISH not amplified) were treated with NLD 50 mg/m2 every three weeks for 3 courses and weekly paclitaxel 80 mg/m2 for 8 courses. 7 patients with HER2 overexpression or FISH amplified were treated with the same schedules plus trastuzumab (Herceptin) 4 mg/kg for the first administration and 2 mg/kg for the following 7 weekly administrations. RESULTS: Pathological complete response (pCR) was documented in 1 patient (treated with trastuzumab); no residual tumor (infiltrating or "in situ") on breast was documented in other 2 patients. Objective clinical responses were documented in 22 patients (73.3%): 8 complete, 10 partial and 4 "minimal" responses. 7 patients have shown stable and 1 progressive disease. Clinical response in patients with HER2 overexpression treated with trastuzumab was 100% (4 complete and 3 partial responses). Conservative surgery was performed in 8 (38%) and mastectomy in 13 (62%) out of 21 operable patients; however, 7 out of 14 responding patients with operable disease underwent quadrantectomy (50%). Main toxicity was neutropenia: febrile in 2 patients (7%) and gr. 3-4 in 13 (43%). Other grade 3 toxicities were as follows: vomiting in 1 patient, asthenia in 1 patient, joint symptom in 1 patient. 3 patients were withdrawn from the study. No episodes of left ventricular ejection fraction (LVEF) < 50% were recorded (with a median reduction of 8%). CONCLUSIONS: A "short course" of paclitaxel and NLD is active in terms of clinical response and conservative surgery for patients with potentially operable and locally advanced breast cancer; toxicity was manageable. High activity of the combination with trastuzumab has been confirmed. However, with this "short course" schedule, the result in term of clinical responses didn't turn into complete pathological responses.

4.
Br J Cancer ; 100(6): 881-7, 2009 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-19259089

RESUMO

The objective of this study was to investigate the efficacy of first-line chemotherapy containing irinotecan and/or oxaliplatin in patients with advanced mucinous colorectal cancer. Prognostic factors associated with response rate and survival were identified using univariate and multivariate logistic and/or Cox proportional hazards analyses. The population included 255 patients, of whom 49 (19%) had mucinous and 206 (81%) had non-mucinous colorectal cancer. The overall response rates for mucinous and non-mucinous tumours were 18.4 (95% CI, 7.5-29.2%) and 49% (95% CI, 42.2-55.8%), respectively (P=0.0002). After a median follow-up of 45 months, median overall survival for the mucinous patients was 14.0 months compared with 23.4 months for the non-mucinous group (hazard ratio (HR), 1.74; CI 95%, 1.27-3.31; P=0.0034). After adjustment for significant features by multivariate Cox regression analysis, mucinous histology was associated with poor overall survival (HR, 1.593, 95% CI, 1.05-2.40; P=0.0267), together with performance status ECOG 2, number of metastatic sites > or =2, and peritoneal metastases. This retrospective analysis shows that patients with mucinous colorectal cancer have poor responsiveness to oxaliplatin/irinotecan-based first-line combination chemotherapy and an unfavourable prognosis compared with non-mucinous colorectal cancer patients.


Assuntos
Adenocarcinoma Mucinoso/tratamento farmacológico , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Compostos Organoplatínicos/administração & dosagem , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Camptotecina/administração & dosagem , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Irinotecano , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Oxaliplatina , Estudos Retrospectivos
5.
Pharmacogenomics J ; 9(1): 78-84, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19104506

RESUMO

The interleukin-1 receptor antagonist (IL-1RA) cytokine is thought to counteract tumor angiogenesis/metastasis. Two single nucleotide polymorphisms in the IL-1RA gene (rs4251961 T/C and rs579543 C/T) influence IL-1RA circulating levels with highest production in carriers of the homozygous rs4251961 T/T and rs579543 T/T genotypes. A total of 180 patients with metastatic colorectal cancer were categorized as high IL-1RA producers if they were carriers of at least one of the rs4251961 T/T or rs579543 T/T genotypes (T/T carriers). Median survival times were 35.8 months (95% confidence interval: 29.7-43.7 months) and 28.6 months (95% confidence interval: 25.6-30 months) in 56 T/T carriers and in 124 non-T/T carriers, respectively. The favorable association between T/T carriers' status and survival was significant in the multivariate analysis (P=0.018). Also, T/T carriers and non-T/T carriers were prevalent among patients with Karnofsky performance status 90-100 and 70-80, respectively (P=0.002). These findings encourage additional studies in this field and the evaluation of a recombinant-IL-1RA for anticancer activity.


Assuntos
Neoplasias Colorretais/genética , Proteína Antagonista do Receptor de Interleucina 1/genética , Polimorfismo de Nucleotídeo Único , Idoso , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Antineoplásicos/uso terapêutico , Cetuximab , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Feminino , Genótipo , Humanos , Proteína Antagonista do Receptor de Interleucina 1/sangue , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica
6.
Br J Cancer ; 99(9): 1402-7, 2008 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-18971936

RESUMO

No established second-line chemotherapy is available for patients with advanced gastric cancer failing to respond or progressing to first-line chemotherapy. However, 20-40% of these patients commonly receive second-line chemotherapy. We evaluated the influence of clinico-pathologic factors on the survival of 175 advanced gastric cancer patients, who received second-line chemotherapy at three oncology departments. Univariate and multivariate analyses found five factors which were independently associated with poor overall survival: performance status 2 (hazard ratio (HR), 1.79; 95% CI, 1.16-2.77; P=0.008), haemoglobin 50 ng ml(-1) (HR, 1.86; 95% CI, 1.21-2.88; P=0.004), the presence of greater than or equal to three metastatic sites of disease (HR, 1.72; 95% CI, 1.16-2.53; P=0.006), and time-to-progression under first-line chemotherapy

Assuntos
Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno Carcinoembrionário/análise , Progressão da Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Neoplasias Gástricas/mortalidade
7.
Br J Cancer ; 99(5): 716-21, 2008 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-18728661

RESUMO

We investigated the association between thymidylate synthase (TS) germline polymorphisms and response to 5-fluorouracil-based chemotherapy in 80 patients with liver-only metastatic colorectal cancer (MCRC). The tandem repeat polymorphism (VNTR) in TS 5'-untranslated region (5'-UTR), which consists of two (2R) or three (3R) 28-bp repeated sequences, with or without a G/C nucleotide change in 3R carriers (3G or 3C) and a 6-bp insertion/deletion (6+/6-) in the TS 3'-UTR, was studied. The distinction between high (2R/3G, 3C/3G and 3G/3G) and low (2R/2R, 2R/3C and 3C/3C) TS expression genotypes according to the 5'-UTR VNTR+G/C nucleotide change showed significant association with tumour response (P=0.01). In particular, high TS expression genotypes were found in 8 out of 34 patients (23.5%) with complete or partial response and in 24 out of 46 patients (52%) with stable disease and disease progression. Liver-only MCRC patients are a homogeneous and clinical relevant subgroup that may represent an ideal setting for studying the actual influence of TS polymorphisms.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/uso terapêutico , Neoplasias Hepáticas/secundário , Polimorfismo Genético , Timidilato Sintase/genética , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/patologia , Feminino , Genótipo , Haplótipos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/enzimologia , Masculino , Análise de Sobrevida , Sequências de Repetição em Tandem , Resultado do Tratamento
8.
Pharmacogenomics J ; 8(4): 278-88, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17549067

RESUMO

The primary end point of the study was the analysis of associations between polymorphisms with putative influence on 5-fluorouracil/irinotecan activity and progression-free survival (PFS) of patients with advanced colorectal cancer treated with first-line FOLFIRI chemotherapy. Peripheral blood samples from 146 prospectively enrolled patients were used for genotyping polymorphisms in thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR), excision repair cross-complementation group-1 (ERCC 1) xeroderma pigmentosum group-D (XPD), X-ray cross-complementing-1 (XRCC 1), X-ray cross-complementing-3 (XRCC 3) and uridine diphosphate-glucuronosyltransferases-A1 (UGT1 A1). TS 3'-UTR 6+/6+ and XRCC3-241 C/C genotypes were associated with adverse PFS. Hazard ratio for PFS achieved 2.89 (95% confidence interval=1.56-5.80; P=0.002) in 30 patients (20%) with both risk genotypes. Risk for Grade III-IV neutropenia was significantly associated with UGT1A1*28 7/7 genotype. These promising findings deserve further investigations and their validation in independent prospective studies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Perfilação da Expressão Gênica/métodos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Camptotecina/análogos & derivados , Camptotecina/farmacologia , Camptotecina/uso terapêutico , Intervalo Livre de Doença , Feminino , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Genótipo , Humanos , Irinotecano , Leucovorina/farmacologia , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Farmacogenética/métodos , Polimorfismo Genético/efeitos dos fármacos , Polimorfismo Genético/genética , Estudos Prospectivos
9.
Minerva Med ; 93(4): 303-7, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12207200

RESUMO

BACKGROUND: Anthracyclines combined with paclitaxel are one of the most active schedules in patients with advanced breast cancer: response rates range from 40 to 80%, considering all metastatic sites (visceral and soft tissues). We performed a non-randomized phase II trial with anthracyclines/paclitaxel combination to evaluate response and toxicity only in patients with visceral metastases. METHODS: Twenty-seven patients (median age 50 years; range 30-72) with visceral metastases of breast cancer were enrolled in this study. Overall, 11 patients had lung metastases (41%), 10 liver (37%), 4 liver-lung metastases (15%) and 2 peritoneal carcinosis (7%). 7 patients had received adjuvant anthracycline-based chemotherapy (26%) and 10 patients adjuvant CMF combination chemotherapy (37%); 10 patients (37%) received hormonal therapy for advanced disease. Treatment schedules were: group A) 17 patients, Adriamicyn 50 mg/m2 on day 1 i.v. bolus and Paclitaxel 175 mg/m2 on day 2 i.v. 3 hours infusion, every 3 weeks; group B) 10 patients, epirubicin 90 mg/m2 on day 1 i.v. bolus and paclitaxel 200 mg/m2 on day 2 i.v., 3 hours infusion, every 3 weeks. The number of cycles administered was 141 with a median of 5 (range 3-9). RESULTS: All patients were evaluable for response and toxicity. The objective response rate was 59% - 16 patients - (15% complete and 44% partial remission), 95% C.I. 40.7-77%; 10/17 in group A and 7/10 in group B. Stable disease 30% (8 patients) and progressive disease 11% (3 patients). The median duration of response was 5 months (range 1-16); median time to progression 13 months (range 3-18) and median survival 17 months (range 4-24). The main toxicity was neutropenia, occurred in 16 patients (59%; grade IV in 7 patients, of whom 2 febrile neutropenia, and grade III in 9 patients); grade III gastrointestinal toxicity in 2 patients; grade III neurological toxicity in 1 patient; grade III stomatitis in 2 patients. No congestive hearth failure or treatment death related was observed. CONCLUSIONS: These schedules of anthracyclines and paclitaxel confirmed their efficacy in metastatic breast cancer even in patients with visceral disease. Neutropenia was the main toxicity; grade IV neutropenia was more frequently observed in epirubicin/paclitaxel arm.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Adulto , Idoso , Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Epirubicina/administração & dosagem , Feminino , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Neoplasias Peritoneais/secundário
10.
Anticancer Res ; 22(5): 3087-92, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12530048

RESUMO

BACKGROUND: Cisplatin/gemcitabine are one of the "standard" chemotherapy schedules in locally advanced and metastatic NSCLC cancer. A number of trials documented that omission of gemcitabine on day 15 and reduction of cisplatin up to 70 mg/mq are equivalent in term of response rates to "classic" administrations on days 1, 8 and 15 with cisplatin 100 mg/mq. The aim of this study was to confirm this evidence and to demonstrate that a further reduction of gemcitabine dose-intensity may be performed with the same efficacy on response. PATIENTS AND METHODS: Fifty untreated patients with locally advanced and metastatic NSCLC entered the study: 24 stage IIIB and 26 stage IV. The median age was 65 years (range 32-76); 44 males and 6 females Genicitabine was administered 1000 mg/mq weekly on days 1 and 8 followed by a 2-week rest and cisplatin 80 mg/mq on day 2 of each 28-day-cycle. RESULTS: Forty-five patients were evaluable for response and all for toxicity. The overall response rates were 35.5% with 16 partial responses (95% Confidence Interval: 32%-61%). Most of the objective responses were seen in IIIB patients (56% of the stage IIIB and 44% of the stage IV patients responded). According to the intent-to-treat-principle, the response rates were 32% (16 out of 50 patients). The median dose-intensity of gemcitabine and cisplatin was respectively 477.6 mg/mq/week (481.4 for responders) and 19.5 mg/mq/week (19.9 mg/mq for responders). The median response duration was 5 months (range 1-18) and the median time to progression was 5 months (1-21); median survival was 9 months (range 2-31). The main toxicity was haematological: thrombocytopenia grade IV in 5 patients (10%) and grade III in 11 patients (22%); neutropenia grade III-IV in 4 patients (8%); grade III anemia in 3 (6%). Asthenia was the most significant non-haematological toxicity and was observed in 19 patients (38%). CONCLUSION: This trial confirmed the efficacy of a schedule with 2 administrations of gemcitabine (on days 1, 8) and a cisplatin dose on day 2 lower than 100 mg/mq. Moreover, the same efficacy was obtained with a median-dose intensity of cisplatin and gemcitabine lower than planned in a 21-day-schedule. For safety and low toxicity, we think that this schedule provides another chance to treat patients with non-small cell lung cancer, especially the elderly or patients with coexistent medical illnesses.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida , Gencitabina
11.
Cancer Invest ; 18(5): 411-6, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10834024

RESUMO

Calcium and antioxidant vitamins, such as A, C, and E, have been shown to reduce colorectal epithelial proliferation and thereby to act as possible chemoprotective agents in colorectal cancer. We investigated the effects of an intervention with calcium and vitamins on cell proliferation in the colonic mucosa of patients operated on for colorectal cancer. Patients with resected colorectal cancer Dukes' stage B-C were randomized to receive daily 30,000 IU of axerophthol palmitate (vitamin A) plus 1 g ascorbic acid (vitamin C) plus 70 mg of dl-alpha-tocopherol acetate (vitamin E) and 2 g natural calcium daily or indistinguishable placebo for 6 months. At the time of surgery and after 6 and 12 months of treatment, cell kinetics of normal colonic mucosa were assessed by using proliferating cell nuclear antigen (PCNA). Ninety patients were enrolled and 77 were assessable: 34 in the treatment group and 43 in the placebo group. A significant reduction of mean total PCNA labeling index (PCNALI) was evident in both groups after 6 months (vitamins/calcium, from 16.11 +/- 2.43 to 10.71 +/- 2.81; placebo, from 17.30 +/- 2.63 to 12.53 +/- 3.40). The difference in the percentage of reduction of mean PCNALI between baseline and after 6 months was not statistically significant in the treatment and placebo groups: 34% and 28%, respectively. A second control, 6 months after discontinuation of vitamin and calcium supplementation, showed a further decrease of mean total PCNALI in both groups, but this was not statistically significant. Our randomized trial showed that calcium and vitamin supplementation does not reduce cell kinetics of colon epithelium. Furthermore, this study suggests the need for extreme caution in the interpretation and publication of studies on chemoprotectants in colon cancer without a control group.


Assuntos
Ácido Ascórbico/farmacologia , Cálcio/farmacologia , Neoplasias Colorretais/prevenção & controle , Vitamina A/farmacologia , Vitamina E/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ácido Ascórbico/administração & dosagem , Cálcio/administração & dosagem , Divisão Celular/efeitos dos fármacos , Quimioprevenção , Neoplasias Colorretais/patologia , Neoplasias Colorretais/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Mucosa Intestinal/citologia , Mucosa Intestinal/efeitos dos fármacos , Cinética , Masculino , Pessoa de Meia-Idade , Vitamina A/administração & dosagem , Vitamina E/administração & dosagem
12.
J Exp Clin Cancer Res ; 19(1): 13-6, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10840930

RESUMO

We report the long-term results of a series of patients affected by advanced epithelial ovarian cancer treated with the PEC combination (cisplatin 60 mg/m2, epirubicin 60 mg/m2 and cyclophosphamide 750 mg/m2, all at day 1, every 21 days). Response was evaluated after three cycles, and treatment continued in responsive patients. A total of 80 patients with a median follow-up of 55 months were studied. Fifty-eight patients with stage III ovarian cancer and 22 patients with stage IV received PEC as primary treatment (41 patients), or for residual disease after surgery (37 patients), or for relapsed disease after primary surgery (2 patients). The overall response rate was 67.5% (20.0% complete response, 47.5% partial response), with 22.5% stable disease and 3.7% progressive disease. Median progression free survival was 13.0 months, and median survival was 25 months. Grade III-IV toxicity was moderate: leukopenia 20.0% of patients, thrombocytopenia 5.0%, anemia 16.2%. No cardiac toxicity was observed. In conclusion, the PEC combination, an anthracycline-containing platinum-based regimen, proved to be effective in advanced ovarian cancer, in terms of response rate and overall survival. The regimen was devoid of significant toxicity and in particular of cardiac toxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cisplatino/administração & dosagem , Ciclofosfamida/administração & dosagem , Epirubicina/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Terapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasia Residual/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Recidiva , Estudos Retrospectivos , Análise de Sobrevida
13.
Support Care Cancer ; 6(2): 139-43, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9540173

RESUMO

Cancer patients with painful osteolytic bone metastases who had failed initial treatment with hormones and/or chemotherapy were each randomized to receive one of three pamidronate doses as outpatients: 45, 60, 90 mg given every 3 weeks for 12 weeks. Seventy patients were enrolled in this study, for a total of 265 infusions. There were 64 patients who completed 12 weeks of therapy. Forty-eight patients took nonsteroidal antinflammatory drugs, while 22 patients received morphine before pamidronate treatment. A reduction in bone pain and mobility scores was observed in all three different dose groups: in 11 of 23 patients (47%) at 45 mg; in 12 of 24 patients (50%) at 60 mg; and in 16 of 23 patients (69%) at 90 mg. However, while for patients receiving pamidronate at 90 mg median changes in pain and mobility were statistically significant at the 6th week, for patients receiving 45 mg they were not significant until the 12th week and for patients receiving 60 mg, until the 9th week. In weeks 0-6, the daily consumption of analgesics was reduced in 3 patients in the 45-mg arm, in 4 patients in the 60-mg arm, and in 7 patients in the 90-mg arm. In weeks 7-12, the daily consumption of analgesics was reduced in 8 patients receiving 45 mg, in 8 patients receiving 60 mg, and in 7 patients receiving 90 mg. No significant toxicity was recorded. In 2 patients (45 and 90 mg) fever (> 38 degrees C) and myalgia were observed after the first administration. In conclusion, our results seem to confirm the utility of higher doses of pamidronate in patients with painful bone metastases, because of the faster symptom relief achieved.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Ósseas/secundário , Carcinoma/secundário , Difosfonatos/administração & dosagem , Dor Intratável/etiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor Intratável/terapia , Pamidronato , Resultado do Tratamento
14.
J Clin Oncol ; 15(11): 3313-9, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9363860

RESUMO

PURPOSE: A multiinstitutional trial was performed to confirm the clinical activity, in terms of response rate and toxicity (primary objectives) and duration of responses and survival (secondary objectives), of an intensive weekly regimen in advanced gastric cancer. PATIENTS AND METHODS: Patients with measurable unresectable and/or metastatic gastric carcinoma received 1-day per week administration of cisplatin (CDDP) 40 mg/m2, fluorouracil (5FU) 500 mg/m2, epi-doxorubicin (epi-ADR) 35 mg/m2, 6S-stereoisomer of leucovorin 250 mg/m2, and glutathione 1.5 g/m2. On the other days, filgrastim was administered by subcutaneous injection at a dose of 5 mg/kg. One cycle of therapy consisted of eight 1-week treatments. Patients who showed a response or stable disease received a further 6 weeks of therapy. RESULTS: Of 105 enrolled patients, 11 had locally advanced unresectable disease only; 33 had primary nonresected and metastatic disease; 48 had metastatic disease and primary tumor resected; 10 had locoregional recurrence and metastatic disease; and three had locoregional recurrence only. After one cycle, 18 complete responses (CRs) and 47 partial responses (PRs) were achieved, for an overall response rate of 62% (95% confidence interval [CI], 53% to 71%). Twenty patients had stable disease and 20 progressed on therapy. The median survival duration of all 105 patients was 11 months, with 1- and 2-year survival rates of 42% and 5%, respectively. World Health Organization (WHO) grade III to IV toxicity, in terms of anemia, neutropenia, thrombocytopenia, and mucositis, was experienced by 40 patients (38%). There were no treatment-related deaths. CONCLUSION: These data support the results of the pilot study and confirmed the high activity of the regimen, with acceptable toxicity. This schedule deserves evaluation in the adjuvant setting.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Análise de Sobrevida
15.
Cancer Chemother Pharmacol ; 38(4): 385-6, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8674163

RESUMO

A total of 26 patients with advanced colorectal cancer received 60 mg/m2 methotrexate i.v. on days 1-4; 400 mg/m2 5-fluorouracil i.v. on days 2, 3, 5, and 6; and 100 mg/m2 6S-leucovorin i.v. on days 2, 3, 5, and 6. Interferon-alpha 2b at a dose of 3 million U was given i.m. daily for the 6 days of chemotherapy. Courses were repeated every 3 weeks. There were four partial responses for a response rate of 15% (95% confidence interval 2-28%): In all, 14 patients expressed grade 3 toxicity; 9 patients had diarrhea, 3 had stomatitis, and 2 developed leukopenia. In conclusion, multimodal biochemical modulation of 5-fluorouracil, at least on this schedule, does not seem to be effective, as it results in severe toxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Esquema de Medicação , Estudos de Viabilidade , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Projetos Piloto , Proteínas Recombinantes , Indução de Remissão
16.
Support Care Cancer ; 4(1): 31-3, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8771291

RESUMO

In an open prospective study. 40 patients with progressing painful bone metastases received 45 mg pamidronate by 1-h infusion every 3 weeks. A total of 27 patients (67%; 95% CI 53%-81%) experienced relief of pain as shown by the significant reduction of the bone pain score after three pamidronate administrations (from 2.25 +/- 0.64 to 1.15 +/- 0.36). Furthermore, 20 patients (60%) reduced their consumption of analgesics. We did not observe any objective response by skeletal radiological examination. In 11 patients presenting a skeletal progressive disease, bone pain improved, as well as their mobility score, but not their fatigue score. Treatment was well tolerated. Only 1 patient discontinued the treatment because of fever and cutaneous rash after the first administration. In conclusion, our results seem to confirm that pamidronate exerts a benefical effect on bone pain and mobility impairment in patients with painful osteolytic bone metastases.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Difosfonatos/uso terapêutico , Dor/tratamento farmacológico , Adulto , Idoso , Neoplasias Ósseas/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Cuidados Paliativos , Pamidronato , Estudos Prospectivos
17.
Oncology ; 52(5): 422-6, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-7637961

RESUMO

The efficacy of recombinant human erythropoietin (rHuEPO) on the increase in hemoglobin levels was assessed in patients with cisplatin (CDDP)-induced anemia older than 70 years. Furthermore, we compared the results obtained in this group of patients with those observed in other patients receiving rHuEPO for a CDDP-associated anemia with similar clinical features (chemotherapeutic regimen, primary tumor; CDDP cumulative dose) but of an age less than 70 years. Twenty patients older than 70 years with a CDDP-associated anemia (hemoglobin levels < 90 milligrams) received rHuEPO at the dose of 100 U/kg subcutaneously, three times a week. The control group consisted of 20 younger patients, anemic after CDDP chemotherapy, treated with rHuEPO. All patients were evaluable for response and toxicity. Hemoglobin concentrations showed a statistically significant increase after the 3rd, 6th and 9th week of therapy in both older (93.1 +/- 10.7, 103.5 +/- 8.2 and 102.7 +/- 8.2, respectively, vs. baseline, 84.6 +/- 4.9) and younger patients (95.3 +/- 11.7, 101.5 +/- 13.4 and 101.9 +/- 8.7, respectively, vs. baseline, 86.6 +/- 4.0). Furthermore, 30% of older patients required blood transfusions versus 35% of younger patients, with the mean unit of blood transfused per patient being 0.7 U in elderly and 0.65 U in younger patients. Treatment was well tolerated with no significant side effects. The CDDP-induced anemia seems to be corrected by rHuEPO also in elderly patients, without differences with respect to younger patients.


Assuntos
Anemia/tratamento farmacológico , Cisplatino/efeitos adversos , Eritropoetina/uso terapêutico , Neoplasias/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Anemia/induzido quimicamente , Cisplatino/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento
18.
Environ Health Perspect ; 102 Suppl 5: 251-2, 1994 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7882944

RESUMO

We report a prevalence study of environmental pleural plaques in subjects over 50 years old from the northeastern Corsican village of Murato, built on asbestos surface deposits. The percentage of plaques was 41%, versus 7.5% in the control village of Vezzani. Although surface deposits contain both chrysotile and tremolite, airborne pollution and asbestos lung burden of exposed inhabitants consist essentially of tremolite as assessed by transmission electron microscopy (TEM). However, TEM analysis of the parietal pleura of three animals bred in exposed areas showed a predominance of short fibers of chrysotile. The respective roles of tremolite and chrysotile in inducing pleural plaques in Corsica should thus be considered.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Asbestose/etiologia , Minerais/análise , Pleura/patologia , Idoso , Animais , Asbestose/epidemiologia , Asbestose/patologia , Cães , Feminino , França/epidemiologia , Cabras , Humanos , Masculino , Pessoa de Meia-Idade , Pleura/metabolismo , Prevalência
19.
Eur Respir J ; 6(7): 978-82, 1993 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8396536

RESUMO

The purpose of this study was to determine whether the inhabitants of villages environmentally exposed to asbestos, in northeast Corsica, had a higher incidence of pleural plaques. X-rays were obtained from subjects aged over 50 yrs, with no occupational exposure to asbestos or history of pleural disease, in one village exposed to asbestos, Murato, and a nonexposed, control village, Vezzani. In addition, the mineral content of the air and parietal pleura of animals in the exposed zone was studied, using transmission electron microscopy. The incidence of bilateral pleural plaques in the exposed population was 41%, as compared to 7.5% in the nonexposed population (p < 0.00001). The levels of airborne tremolite were higher in Murato (6-72 ng.m-3) than in Vezzani (< 1 ng.m-3), but chrysotile levels were similar. Significant numbers of chrysotile and tremolite fibres were identified in the parietal pleura of animals from the exposed village. This study confirms the well-known correlation between bilateral pleural plaques and environmental exposure to low levels of asbestos.


Assuntos
Amiantos Anfibólicos , Amianto , Asbestose/epidemiologia , Exposição Ambiental , Doenças Pleurais/epidemiologia , Ácido Silícico , Idoso , Poluentes Atmosféricos/análise , Animais , Asbestos Serpentinas , Cães , Feminino , França/epidemiologia , Cabras , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pleura/química , Prevalência
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