RESUMEN
BACKGROUND: Treatment with oxaliplatin plus raltitrexed has demonstrated an encouraging therapeutic index in patients with advanced colorectal cancer and malignant pleural mesothelioma. The aim of this multi-institutional study was to determine the antitumor potential of this combination in patients with metastatic gastric cancer failing prior palliative first-line chemotherapy, and to reconfirm its favorable toxicity profile. PATIENTS AND METHODS: 21 patients with metastatic gastric cancer, who progressed while on or within 6 months after discontinuing palliative first-line chemotherapy, participated in this study. They received raltitrexed 3,0 mg/m(2) and oxaliplatin 130 mg/m(2) both given intravenously on day 1 every 3 weeks. RESULTS: One patient achieved a partial response, 6 had stable disease, and 14 patients progressed. Median progression-free and overall survival from the onset of salvage chemotherapy was 2.0 and 4.5 months, respectively. Hematologic adverse reactions, specifically neutropenia and anemia were common, though generally mild to moderate with only 3 patients experiencing grade 3/4 toxicity. The most frequent non-hematologic adverse events included nausea/emesis, asthenia, and transient elevation of liver functional parameters, again with grade 3 symptoms occurring only in a minority of patients. CONCLUSION: Despite reproducibility of a favorable toxicity profile of oxaliplatin + raltitrexed, our data suggest that this combination regimen has no substantial antitumor activity in patients with progressive, chemotherapeutically pretreated metastatic gastric cancer.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cuidados Paliativos , Terapia Recuperativa , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Oxaliplatino , Quinazolinas/administración & dosificación , Quinazolinas/efectos adversos , Retratamiento , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Tasa de Supervivencia , Tiofenos/administración & dosificación , Tiofenos/efectos adversosRESUMEN
There is no established second-line treatment for advanced pancreatic cancer after gemcitabine failure. In view of the urgent need for such therapy, and since preclinical and phase I clinical data suggest an encouraging, potentially synergistic activity between raltitrexed and irinotecan, the present randomised phase II study was initiated. A total of 38 patients with metastatic pancreatic adenocarcinoma, who progressed while receiving or within 6 months after discontinuation of palliative first-line chemotherapy with gemcitabine, were enrolled in this study. They were randomised to 3-weekly courses of raltitrexed 3 mg x m(-2) on day 1 (arm A) or irinotecan 200 mg x m(-2) on day 1 plus raltitrexed 3 mg x m(-2) on day 2 (arm B). The primary study end point was objective response, secondary end points included progression-free survival (PFS) and overall survival (OS), as well as clinical benefit response in symptomatic patients (n=28). In the combination arm, the IRC-confirmed objective response rate was 16% (three out of 19 patients had a partial remission; 95% CI, 3-40%), which was clearly superior to that in the comparator/control arm with raltitrexed alone, in which no response was obtained. Therefore, the trial was already stopped at the first stage of accrual. Also, the secondary study end points, median PFS (2.5 vs 4.0 months), OS (4.3 vs 6.5 months), and clinical benefit response (8 vs 29%) were superior in the combination arm. The objective and subjective benefits of raltitrexed+irinotecan were not negated by severe, clinically relevant treatment-related toxicities: gastrointestinal symptoms (42 vs 68%), partial alopecia (0 vs 42%), and cholinergic syndrome (0 vs 21%) were more commonly noted in arm B; however, grade 3 adverse events occurred in only three patients in both treatment groups. Our data indicate that combined raltitrexed+irinotecan seems to be an effective salvage regimen in patients with gemcitabine-pretreated pancreatic cancer. The superior response activity, PFS and OS (when compared to raltitrexed), as well as its tolerability and ease of administration suggest that future trials with this combination are warranted.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antineoplásicos/toxicidad , Camptotecina/análogos & derivados , Camptotecina/toxicidad , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamiento farmacológico , Quinazolinas/toxicidad , Tiofenos/toxicidad , Adenocarcinoma/mortalidad , Adulto , Anciano , Antimetabolitos Antineoplásicos/uso terapéutico , Antimetabolitos Antineoplásicos/toxicidad , Antineoplásicos/uso terapéutico , Camptotecina/administración & dosificación , Camptotecina/uso terapéutico , Desoxicitidina/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Humanos , Irinotecán , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/mortalidad , Quinazolinas/administración & dosificación , Quinazolinas/uso terapéutico , Análisis de Supervivencia , Tiofenos/administración & dosificación , Tiofenos/uso terapéutico , Factores de Tiempo , Resultado del Tratamiento , GemcitabinaRESUMEN
BACKGROUND: Gemcitabine is an active antitumor agent in the treatment of advanced pancreatic cancer, and has shown potential synergistic activity with the oral fluoropyrimidine capecitabine in previous phase I/II trials. Based on this background and in order to define the therapeutic potential and tolerance of this combination more precisely, the present randomized multicenter phase II trial was initiated. PATIENTS AND METHODS: We prospectively randomized 83 patients to treatment with biweekly gemcitabine 2,200 mg/m(2) given as a 30 min intravenous infusion on day 1, or the same treatment plus oral capecitabine 2,500 mg/m(2) given from days 1 to 7. In both arms, chemotherapy was administered for a duration of 6 months unless there was prior evidence of progressive disease. The efficacy of the two treatment arms was evaluated according to standard criteria, i.e. objective response, progression-free survival (PFS) and overall survival (OS), as well as by analysis of clinical benefit response. RESULTS: The overall objective response rate among the 42 patients treated with gemcitabine alone was 14% compared with 7/41 (17%) among those treated with the combination arm. Similar to response rates, there was no apparent difference between the two groups in terms of median PFS (4.0 versus 5.1 months) and median OS (8.2 versus 9.5 months) in the gemcitabine and combination arm, respectively. Of 61 patients with tumor-related symptoms, who were considered evaluable for clinical benefit response, 10/30 (33%) and 15/31 (48.4%) experienced significant palliation in the gemcitabine and combination arm, respectively. Chemotherapy was well tolerated in both arms with only four versus six patients experiencing WHO grade 3 symptoms. Apart from the occurrence of hand-foot syndrome in 10 patients, no major increase in incidence and/or degree of adverse reactions was noted in the combination arm. CONCLUSIONS: Results of this trial suggest a fairly good therapeutic index for the combination of biweekly high-dose gemcitabine and capecitabine for the treatment of advanced pancreatic cancer. Despite a somewhat superior clinical benefit response rate, no advantage over single-agent gemcitabine, however, was noted in terms of objective efficacy parameters.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamiento farmacológico , Adenocarcinoma/secundario , Neoplasias de las Glándulas Suprarrenales/tratamiento farmacológico , Neoplasias de las Glándulas Suprarrenales/secundario , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Capecitabina , Desoxicitidina/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/análogos & derivados , Enfermedad de Boca, Mano y Pie/etiología , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Metástasis Linfática , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Neoplasias Pancreáticas/patología , Estudios Prospectivos , Tasa de Supervivencia , Síndrome , Resultado del Tratamiento , GemcitabinaRESUMEN
BACKGROUND: Breast cancer metastasizing to the liver with presence of a parenchymatous icterus presents a therapeutic dilemma. Treatment-related toxicity can be unpredictable due to altered drug clearance, and bilirubin exceeding 5,0 mg/dl is generally considered an absolute contraindication for the administration of cytotoxic agents. The pharmacokinetics of capecitabine--an active oral 5-fluorouracil prodrug for the treatment of advanced breast cancer--are not affected in patients with mild to moderate hepatic dysfunction, but there are no data available for patients with severe hyperbilirubinemia. PATIENT AND METHODS: We herein report the case of a female patient with advanced breast cancer with predominant liver metastases and severe hyperbilirubinemia (12 mg/dl). The patient received oral capecitabine at a dose of 2,500 mg/m2/day in 2 divided doses for 2 weeks, followed by 1 week rest. RESULTS: Several assessments of liver function parameters including serum bilirubin showed a decrease to normal values within 2.5 months. After 7 courses of treatment, a partial remission was confirmed by CT scan. Treatment with capecitabine was well tolerated with grade 2 hand-and-foot syndrome and mild nausea being the only side effects. CONCLUSION: This case report suggests that capecitabine can be safely administered without dose adjustment in patients with extensive liver metastases and hepatic dysfunction.
Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Antineoplásicos Hormonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Hiperbilirrubinemia/tratamiento farmacológico , Pruebas de Función Hepática , Neoplasias Hepáticas/secundario , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Profármacos/administración & dosificación , Terapia Recuperativa , Antimetabolitos Antineoplásicos/efectos adversos , Antimetabolitos Antineoplásicos/farmacocinética , Antineoplásicos Hormonales/efectos adversos , Antineoplásicos Hormonales/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Neoplasias Óseas/sangre , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/patología , Neoplasias Óseas/secundario , Neoplasias de la Mama/sangre , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Capecitabina , Terapia Combinada , Desoxicitidina/efectos adversos , Desoxicitidina/farmacocinética , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/análogos & derivados , Humanos , Hiperbilirrubinemia/sangre , Hiperbilirrubinemia/etiología , Hiperbilirrubinemia/patología , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Mastectomía , Persona de Mediana Edad , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Neoplasias Hormono-Dependientes/sangre , Neoplasias Hormono-Dependientes/patología , Neoplasias Hormono-Dependientes/cirugía , Profármacos/efectos adversos , Profármacos/farmacocinética , RetratamientoRESUMEN
BACKGROUND: The aim of this phase I study was to determine the maximum-tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of an intermittent weekly capecitabine regimen in combination with oxaliplatin. Furthermore, we intended to explore its safety at the recommended dose, and to assess its principal antitumor activity in patients with advanced colorectal cancer. PATIENTS AND METHODS: Thirty patients with measurable metastatic colorectal cancer who previously were unexposed to palliative chemotherapy were enrolled on to this disease-oriented phase I trial. They were treated with a fixed dose of oxaliplatin (85 mg/m(2) administered as a 2-h intravenous infusion on day 1) plus escalating doses of capecitabine (given at two divided daily doses from days 1 to 7), repeated every 2 weeks. The dose of oral fluoropyrimidine was escalated in consecutive cohorts of three to six patients from 2500 to 4000 mg/m(2)/day. After having defined the toxic dose, nine additional patients were entered at the MTD/recommended dose to confirm its safety profile, and assure suitability for future phase II/III studies. RESULTS: In the phase I part of the study, 21 patients were enrolled, and a total of 222 courses were administered through four dose levels of capecitabine combined with oxaliplatin 85 mg/m(2). Gastrointestinal toxicities, predominantly diarrhea, were the principal DLTs. Other severe adverse events included grade 3 asthenia, acute neurological symptoms and skin toxicity. The combination was not myelosuppressive, eliciting only sporadically grade 3/4 neutropenia and/or thrombocytopenia. There was no alopecia, and only a few patients experienced mild symptoms of hand-foot syndrome. Externally reviewed objective responses were noted in 15 of all 30 evaluable patients (overall response rate, 50%; 95% confidence interval 31% to 69%) including three complete remissions and median progression-free survival was 8.8 months (range 7-14+ months). CONCLUSIONS: Overall results of this study indicate that the administration of clinically relevant single-agent doses of both capecitabine and oxaliplatin is feasible and seems to result in promising therapeutic activity in patients with advanced colorectal cancer. On the basis of the toxicological profile of the combination regimen shown in the present study, oxaliplatin 85 mg/m(2) as a 2-h intravenous infusion every 2 weeks administered in combination with capecitabine 3500 mg/m(2)/day x7 in two divided doses is recommended for further evaluations.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Administración Oral , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Capecitabina , Neoplasias Colorrectales/patología , Desoxicitidina/administración & dosificación , Diarrea/inducido químicamente , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Fluorouracilo/análogos & derivados , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Cuidados Paliativos , Resultado del TratamientoRESUMEN
BACKGROUND: Both oxaliplatin and irinotecan have demonstrated antitumor activity in pretreated colorectal cancer; experimental and early clinical data suggest that these two drugs may act synergistically. The aim of this study was to document the therapeutic index of a biweekly combination regimen in patients with metastatic colorectal cancer failing prior palliative first-line chemotherapy with raltitrexed. PATIENTS AND METHODS: In this study 27 patients with metastatic colorectal cancer were analyzed, who progressed while on or within 6 months after discontinuation of palliative first-line chemotherapy with raltitrexed. They received oxaliplatin 85 mg/m(2) and irinotecan 150 mg/m(2) both given on days 1 and 15 every 4 weeks. RESULTS: The confirmed overall response rate was 37% (95% confidence interval, 19.4-57.7%), including 2 complete and 8 partial remissions. 12 additional patients (44.4%) had stable disease, and in only 5 cases (18.5%) disease progression was not influenced by chemotherapy. The median progression-free survival for all 27 patients was 8 months (range, 1-16+ months), and 16 patients (59%) are still alive after a median follow-up time of 12.5 months. Hematologic adverse reactions, specifically leukocytopenia and neutropenia, were common though generally mild to moderate with grade 4 toxicity occurring in only 2 cases. The most frequent non-hematologic adverse events included gastrointestinal symptoms; severe nausea/emesis and diarrhea, however, were noted in only 2 and 3 patients, respectively. CONCLUSIONS: Our data suggest that the described biweekly combination regimen of oxaliplatin and irinotecan has substantial antitumor activity in patients with progressive, raltitrexed-pretreated metastatic colorectal cancer. Because of its favorable toxicity profile, further evaluation of this combination seems warranted.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Camptotecina/análogos & derivados , Camptotecina/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Compuestos Organoplatinos/administración & dosificación , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Camptotecina/efectos adversos , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Irinotecán , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Compuestos Organoplatinos/efectos adversos , Oxaliplatino , Cuidados Paliativos , Quinazolinas/administración & dosificación , Quinazolinas/efectos adversos , Tiofenos/administración & dosificación , Tiofenos/efectos adversos , Insuficiencia del TratamientoAsunto(s)
Antineoplásicos/efectos adversos , Neoplasias Colorrectales/tratamiento farmacológico , Enfermedades del Sistema Nervioso/inducido químicamente , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Compuestos Organoplatinos/efectos adversos , Ácido Tióctico/uso terapéutico , Anciano , Antineoplásicos/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/uso terapéutico , Oxaliplatino , Resultado del TratamientoRESUMEN
A phase II trial was performed to determine the antitumour efficacy and tolerance of combined paclitaxel and cisplatin with or without hematopoetic growth factor support in patients with advanced gastric cancer. Forty-five patients with histologically confirmed metastatic gastric cancer were entered in this trial. Treatment consisted of 2-weekly courses of paclitaxel 160 mg per m2 and cisplatin 60 mg per m2 both given on day 1. Depending on absolute neutrophil counts on the days of scheduled chemotherapeutic drug administration (1000-2000 per microl), a 5-day course of human granulocyte colony-stimulating factor 5 microg x kg(-1) per day was given subcutaneously; in addition, if haemoglobin was <12.0 mg dl(-1), erythropoietin 10 000 IU was administered subcutaneously three times per week. The confirmed overall response rate (intent-to-treat) was 44%, including five complete (11%) and 15 partial remissions (33%). Twelve patients had stable disease (27%), 11 (24%) progressed while on chemotherapy, and two patients were not evaluable. The median time to response was 3 months, the median time to progression 7.0 months, and the median survival time was 11.2 months with 12 patients currently alive. Haematologic toxicity was common, though WHO grade 4 neutropenia occurred in only five patients (11%). Apart from total alopecia in 16 patients (36%), severe non-haematologic adverse reactions included grade 3 peripheral neuropathy in six (13%) and anaphylaxis in two patients. In addition, there was one patient each who experienced grade 3 emesis, diarrhea, and infection, respectively. Our data suggest that the combination of paclitaxel and cisplatin with or without G-CSF and/or erythropoietin has promising therapeutic activity in patients with advanced gastric cancer.
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Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Eritropoyetina/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Eritropoyetina/efectos adversos , Femenino , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Enfermedades Hematológicas/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE: We assessed the influence of hemoglobin level and r-HuEPO administration on response to chemoradiotherapy, locoregional tumor control, and overall survival in patients treated with neoadjuvant chemoradiotherapy and surgery for a squamous cell carcinoma of the oral cavity or oropharynx. METHODS AND MATERIALS: The 191 study patients were treated with mitomycin C (15 mg/m(2) day 1), 5-fluorouracil (750 mg/m(2)/day, days 1-5), and radiotherapy (50 Gy in 25 fractions weeks 1-5), followed by resection of the primary tumor bed and neck dissection at the General Hospital Vienna, Austria, between November 1989 and October 1998 for a T2-4, N0-3, M0 SCC of the oral cavity or oropharynx. Starting in May 1996, patients with a low hemoglobin (Hgb) before or during chemoradiotherapy received r-HuEPO 10,000 IU/kg s.c. 3-6 times/week until the week of surgery. RESULTS: On multivariate analysis, Hgb level and use of r-HuEPO were independent prognostic factors for response to chemoradiotherapy and locoregional tumor control (p < 0.01). Pathologic response to neoadjuvant therapy was also predictive of locoregional control (p < 0.001). Patients with a pretreatment Hgb > or = 14.5 g/dL had significantly higher complete response, locoregional control, and survival rates than the patients with a pretreatment Hgb < 14.5 g/dL who did not receive r-HuEPO (p < 0.05). The response, control, and survival rates in patients with a pretreatment Hgb < 14.5 g/dL given r-HuEPO were significantly higher than in low Hgb patients not given r-HuEPO (p < or = 0.001) and equivalent to patients with a pretreatment Hgb > 14.5 g/dL (p > or = 0.3). CONCLUSION: Low pretreatment Hgb is a negative prognostic factor for oral cavity and oropharyngeal SCCA patients, but was completely abrogated by r-HuEpo administration during neoadjuvant chemoradiotherapy. Randomized trials of radiation and/or chemotherapy with or without r-HuEPO for patients whose Hgb level is either low at the start of therapy or is anticipated to become low during therapy are indicated.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/terapia , Eritropoyetina/uso terapéutico , Hemoglobinas/metabolismo , Neoplasias de la Boca/sangre , Neoplasias de la Boca/terapia , Neoplasias Orofaríngeas/sangre , Neoplasias Orofaríngeas/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Células Escamosas/patología , Eritropoyetina/efectos adversos , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Mitomicina/administración & dosificación , Mitomicina/efectos adversos , Neoplasias de la Boca/patología , Terapia Neoadyuvante , Estadificación de Neoplasias , Neoplasias Orofaríngeas/patología , Cuidados Preoperatorios , Proteínas Recombinantes , Estudios RetrospectivosRESUMEN
INTRODUCTION: Until today, an optimal palliative treatment regimen has not been defined for patients with advanced hepatocellular carcinoma. Since the novel cytidine analog gemcitabine has shown strong antitumor effects in vitro in a human hepatoma cell line and its therapeutic potential seems well established in several different tumors including gastrointestinal adenocarcinomas, the present phase II trial using a dose-intensified biweekly administration schedule was initiated. PATIENTS AND METHODS: 17 patients with histologically confirmed unresectable advanced or metastatic hepatoma were treated with gemcitabine 2,200 mg/m(2) given as a 30-min intravenous infusion on days 1 and 15. Treatment courses were repeated every 4 weeks. RESULTS: All patients were evaluable for response and toxicity assessment. No objective response was achieved, stable disease occurred in 8 patients (47%), and 9 progressed while on chemotherapy. The median time to progression was 4 months (range 1.5-14 months), and the median survival time was 8.5 months (range 2.5-16.0+ months). Treatment was well tolerated with mild or moderate leukopenia, thrombocytopenia and anemia representing the most common side effects. Gastrointestinal and other subjective toxicities were infrequent and also generally mild. CONCLUSIONS: In view of the disappointing treatment results, gemcitabine using this particular dose regimen should not be considered for further investigation in patients with advanced hepatocellular carcinoma.
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Antimetabolitos Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Desoxicitidina/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Adulto , Anciano , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Carcinoma Hepatocelular/mortalidad , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Femenino , Humanos , Infusiones Intravenosas , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Tasa de Supervivencia , Resultado del Tratamiento , GemcitabinaAsunto(s)
Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Hipotensión/inducido químicamente , Compuestos Organoplatinos/efectos adversos , Corticoesteroides/uso terapéutico , Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Fluorouracilo/administración & dosificación , Antagonistas de los Receptores Histamínicos H1/uso terapéutico , Humanos , Infusiones Intravenosas , Leucovorina/administración & dosificación , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/secundarioRESUMEN
BACKGROUND: Oxaliplatin is a novel cytotoxic agent with documented activity in colorectal cancer. Side effects are generally moderate, and include peripheral neuropathy along with mild bone marrow suppression and gastrointestinal side effects. To our knowledge, induction of febrile episodes by this agents has not been described in the literature. CASE REPORT: We present the case of a 74-year-old male patient admitted to our institution for palliative treatment of metastatic colorectal carcinoma. Due to progression during treatment with 5-fluorouracil and leucovorin, chemotherapy consisting of oxaliplatin 85 mg/m(2) on days 1 + 15 plus mitomycin C 8 mg/m(2) on day 1 repeated every 28 days was initiated. The first cycle of this combination was tolerated without side effects, but the patient experienced fever up to 39 degrees C starting 2 h after oxaliplatin administration on day 15 of the second cycle, which persisted for 3 days. Fever again recurred at the same interval following administration of oxaliplatin on day 1 of the next cycle. Blood samples taken at regular intervals disclosed an increase in IL-6 serum levels parallel to the body temperature curve, with the peak corresponding to the highest temperature, while C-reactive protein values remained unchanged. In spite of intensive premedication with steroids, antipyretics and clarithromycin, fever promptly recurred during the third cycle of treatment. CONCLUSION: Our data suggest a clear- cut correlation between fever, the release of IL-6 and oxaliplatin administration. Whether IL-6 release is directly triggered by the application of oxaliplatin or is a bystander phenomenon, however, remains unclear at the moment.
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Antineoplásicos/efectos adversos , Fiebre/inducido químicamente , Interleucina-6/metabolismo , Compuestos Organoplatinos/efectos adversos , Adenocarcinoma/sangre , Adenocarcinoma/tratamiento farmacológico , Anciano , Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/tratamiento farmacológico , Fiebre/sangre , Humanos , Interleucina-6/sangre , Masculino , Compuestos Organoplatinos/uso terapéutico , OxaliplatinoAsunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina , Captopril/farmacología , Dipéptidos/metabolismo , Prolina/análogos & derivados , Glándulas Suprarrenales/metabolismo , Animales , Disponibilidad Biológica , Biotransformación , Encéfalo/metabolismo , Dipéptidos/sangre , Dipéptidos/farmacología , Enalapril , Hidrólisis , Riñón/metabolismo , Pulmón/metabolismo , Masculino , Ratas , Ratas EndogámicasRESUMEN
Intravenous administration of captopril (20 micrograms) produced inhibition of angiontensin I pressor responses by 70 percent and of plasma-converting enzyme activity by 72 percent. Oral treatment with captopril (50 mg/kg/day) for 1 week inhibited angiotensin I pressor responses more (84 percent) than plasma-converting enzyme activity (23 percent). Four month oral treatment of normotensive and spontaneously hypertensive rats with captopril (50 mg/kg/day) led to 68 and 71 percent inhibition of angiotensin I pressor responses, but produced increases in plasma-converting enzyme activity of 123 and 94 percent, respectively. In spontaneously hypertensive rats, elevated converting enzyme activity in the medulla oblongata was measured after this treatment. It is concluded that plasma-converting enzyme activity measurements can be dissociated from the in vivo inhibition of converting enzyme. Chronic oral captopril treatment results in an induction of converting enzyme biosynthesis not only in peripheral tissue but also in the brain.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina , Captopril/farmacología , Prolina/análogos & derivados , Angiotensina I/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/enzimología , Hipertensión/tratamiento farmacológico , Hipertensión/enzimología , Masculino , Ratas , Ratas Endogámicas , Sistema Renina-Angiotensina/efectos de los fármacosRESUMEN
Intravenous Captopril (20 microgram) in rats produced similar inhibition of the pressor responses to intravenous ANG I (70%) and of plasma-converting enzyme activity (CEA) measured fluorometrically (72%). One week oral treatment with Captopril (50 mg/kg per day) inhibited ANG I pressor responses more (84%) than plasma CEA (23%). Four-month oral treatment of normotensive and spontaneously hypertensive rats with Captopril (50 mg/kg per day) led to a 68% and 71% inhibition of the ANG I pressor responses, but to a 123% and 94% increase of plasma CEA, respectively. Thus, plasma CEA measurements can be dissociated from the in vivo inhibition of converting enzyme (CE). Chronic oral Captopril treatment induces CE biosynthesis.
Asunto(s)
Captopril/farmacología , Hipertensión/tratamiento farmacológico , Peptidil-Dipeptidasa A/sangre , Prolina/análogos & derivados , Angiotensina I/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Captopril/uso terapéutico , Masculino , Ratas , Ratas EndogámicasRESUMEN
In rats, immunoreactivity was demonstrated in the brush border of the choroid plexus, in the wall of blood vessels in the brain, and in the brush border of the proximal tubules of the kidney, using the peroxidase-antiperoxidase technique (PAP) and an anti-pulmonary converting-enzyme antibody. These findings correlate with biochemical data of converting-enzyme activity in the choroid plexus and in other tissues. Possible functions of the enzyme in relation to its localization are discussed.