RESUMEN
High-dose chemotherapy and hematopoietic stem cell support remains a curative treatment option for relapsed or nonresponsive germ cell tumors, and has been applied experimentally to control severe autoimmune diseases. In the present study, we report on a patient with systemic lupus erythematosus nephritis who developed a nonseminomatous germ cell tumor that relapsed after standard chemotherapy and surgery. The patient received high-dose chemotherapy supported by autologous hematopoietic cell transplantation based on its indication for relapsed germ cell tumors. Prolonged control of his relapsed germ cell tumor and systemic lupus erythematosus was attained with high-dose chemotherapy and hematopoietic stem cell support. An extensive literature review is provided alongside a detailed discussion of the aforementioned case.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Lupus Eritematoso Sistémico/prevención & control , Nefritis Lúpica/prevención & control , Recurrencia Local de Neoplasia/prevención & control , Neoplasias de Células Germinales y Embrionarias/prevención & control , Terapia Recuperativa , Adulto , Carboplatino/administración & dosificación , Terapia Combinada , Ciclofosfamida/administración & dosificación , Etopósido/administración & dosificación , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/patología , Nefritis Lúpica/complicaciones , Nefritis Lúpica/patología , Masculino , Recurrencia Local de Neoplasia/etiología , Recurrencia Local de Neoplasia/patología , Neoplasias de Células Germinales y Embrionarias/etiología , Neoplasias de Células Germinales y Embrionarias/patología , Pronóstico , Trasplante Autólogo , Adulto JovenRESUMEN
BACKGROUND: Renal cell carcinoma (RCC) may involve both kidneys. When bilateral nephrectomy is necessary renal replacement therapy is mandatory. Treating such patients with sequential therapy based on cytokines, antiangiogenic factors and mammalian target of rapamycin (mTOR) inhibitors is challenging. CASE PRESENTATION: The first case, a 50-year-old Caucasian female, underwent a radical right nephrectomy for RCC. Twelve years later she underwent a radical left nephrectomy along with total hysterectomy including bilateral salpingo-oophorectomy for RCC involving the right kidney and ovary. Hemodialysis was necessary because of bilateral nephrectomy. She relapsed with pulmonary metastases and enlarged mediastinal lymph nodes and received cytokine based therapy along with bevacizumab. Therapy was discontinued despite the partial response because of hemorrhagic gastritis. Therapy was switched to an antiangiogenic factor but the patient manifested a parietal brain hematoma and stopped therapy. Subsequently disease relapsed with malignant pleural effusion and pulmonary nodules and a mammalian target of rapamycin inhibitor was administered which was withdrawn only at patient's deteriorating performance status. The patient died of the disease 13 years after the initial diagnosis of RCC. CONCLUSION: Patients with RCC are in significant risk to manifest bilateral disease. Renal insufficiency requiring hemodialysis poses therapeutic challenges. Clinicians must be aware of the antiangiogenic factors' adverse effects, especially bleeding, that may manifest in higher frequency and more severe in this setting.
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Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/secundario , Neoplasias Renales/diagnóstico , Neoplasias Renales/secundario , Diálisis Renal/tendencias , Carcinoma de Células Renales/cirugía , Femenino , Humanos , Neoplasias Renales/cirugía , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND: Adenocarcinoma of the pancreas only rarely is associated with inflammatory myopathy. In this setting, polymyositis may be treated with glucocorticoids in combination with cancer specific treatment. CASE PRESENTATION: We present the case of a 52-year-old man with stage IIA pancreatic tail adenocarcinoma who underwent surgical treatment and six months into therapy with gemcitabine he developed symmetrical, painful, proximal muscle weakness with peripheral oedema. Re-evaluation with imaging modalities, muscle histology and biochemistry conferred the diagnosis of polymyositis associated with pancreatic cancer progression. The patient was treated with glucocorticoids along with gemcitabine and erlotinib which resulted in complete remission within six months. He remained in good health for a further six months on erlotinib maintenance therapy when a new computer tomography scan showed pancreatic cancer relapse and hence prompted 2nd line chemotherapy with gemcitabine. CONCLUSIONS: Polymyositis associated with pancreatic cancer may respond to glucocorticoids along with cancer specific treatment.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antimetabolitos Antineoplásicos/efectos adversos , Desoxicitidina/análogos & derivados , Glucocorticoides/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Polimiositis/inducido químicamente , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/cirugía , Antimetabolitos Antineoplásicos/uso terapéutico , Linfocitos T CD8-positivos/efectos de los fármacos , Desoxicitidina/efectos adversos , Desoxicitidina/uso terapéutico , Clorhidrato de Erlotinib , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/cirugía , Polimiositis/tratamiento farmacológico , Polimiositis/patología , Quinazolinas/uso terapéutico , Cintigrafía , GemcitabinaRESUMEN
OBJECTIVE: This study was conducted to investigate the efficacy and safety of gabapentin monotherapy in the management of chemotherapy-induced neuropathic pain. PATIENTS: Seventy-five cancer patients who had previously received chemotherapy, and had experienced at least one symptom of neuropathic pain were included in the intervention group. They received a fixed low-dose of gabapentin (800 mg/day). The control group consisted of 35 cancer patients with similar treatment history and symptomatology, who refused treatment with gabapentin and, therefore, received a fixed-dose combination of naproxen and codeine/paracetamol. OUTCOME MEASURES: Patients were grouped in three categories according to the severity of their neuropathic symptoms at baseline: mild, moderate, and severe. Analgesic efficacy of the study drug was assessed by means of a patient-answered questionnaire. Four stages of analgesic response were established: complete, partial, minor, and no response. RESULTS: All patients completed the study and were evaluable. In the intervention arm, gabapentin led to a complete response in 25.3% of patients (19/75), partial response in 44% (33/75), minor response in 25.3% (19/75), and no response in 5.3% (4/75). The response to gabapentin correlated with the severity of the underlying neurotoxicity. Approximately 25% of patients receiving gabapentin experienced mild somnolence, but none discontinued it. In the control group, none experienced complete response (0/35), while partial, minor, and no response were observed in 5.7% (2/35), 45.7% (16/35), and 48.6% (17/35), respectively. Compared with the control group, gabapentin therapy led to a statistically significant better response in patients of each baseline neurotoxicity group. CONCLUSIONS: Gabapentin monotherapy seems to be well tolerated and useful for the management of chemotherapy-induced neuropathic pain.
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Aminas/uso terapéutico , Analgésicos/uso terapéutico , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Neuralgia , Ácido gamma-Aminobutírico/uso terapéutico , Adulto , Anciano , Femenino , Gabapentina , Humanos , Masculino , Persona de Mediana Edad , Neuralgia/inducido químicamente , Neuralgia/tratamiento farmacológico , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: Treatment options in patients with recurrent non-small cell lung cancer (NSCLC) remain limited as a result of poor activity of most agents after failure of platinum-based therapy. In the present phase I-II study, we evaluated the feasibility and efficacy of bi-weekly gemcitabine (GEM) + irinotecan (CPT-11) in patients with relapsed NSCLC. PATIENTS AND METHODS: Patients with advanced NSCLC, WHO-performance status (PS) = 2, prior taxane/platinum-based chemotherapy were eligible. Chemotherapy was administered in a dose-escalated fashion in subgroups of 3-6 patients until dose-limiting toxicity (DLT) was encountered as follows: CPT-11 150 or 180 mg/m(2) followed by GEM 1,200-1,800 mg/m(2), both on days 1 + 15, recycled every 28 days in four dose levels (DLs). RESULTS: Forty-nine patients entered the phase I and II part of the study (phase I: 12-phase II: 37 + 3 at DL-3), and 40 patients were evaluable for a response in phase II and all for toxicity: median age, 61 years (range 36-74); PS, 1 (0-2); gender, 43 males/6 females-histologies; adenocarcinoma, 25; squamous, 20; large cell, 4. Metastatic sites included lymph nodes, 38; bone, 5; liver, 4; brain, 3; lung nodules, 14; adrenals, 13; other, 3. All patients had prior taxane + platinum-based treatment, and 42 patients had prior docetaxel-ifosfamide-cisplatin/or-carboplatin regimens. DLT was observed at DL-4 and included 2/3 cases with grade 3 diarrhea-1/3 of these with febrile neutropenia. The recommended DL for phase II evaluation was DL3: GEM, 1,500 + CPT-11-180 mg/m(2). Objective responses in phase II were PR, 6/40 [15%; 95% confidence interval (CI), 5-31%]; stable disease, 16/40 (40%; 95% CI, 21-53%); and progressive disease, 18/40 (45%; 95% CI, 28.5-62.5%). The median time-to-progression was 4 months (range 1-12) and median survival 7 months (range 1.5-42 +), while 1-year survival was 20%. Grade 3/4 neutropenia was seen in 18% of patients (6% grade 4) and 6% incidence of febrile neutropenia. No Grade 3/4 thrombocytopenia were seen, grade 3 diarrhea in 6% of patients and grade 2 in 15% of patients, while other grade 3 non-hematologic toxicities were never encountered. CONCLUSIONS: Bi-weekly GEM + CPT-11 is active and well tolerated in patients with advanced NSCLC failing prior taxane + platinum regimens, and represents an effective and convenient combination to apply in the palliative treatment of relapsed NSCLC particularly after failure of first-line docetaxel + platinum-based regimens.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Antibióticos Antineoplásicos/administración & dosificación , Antineoplásicos/administración & dosificación , Antineoplásicos Fitogénicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Recuento de Células Sanguíneas , Hidrocarburos Aromáticos con Puentes/administración & dosificación , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/psicología , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Diarrea/inducido químicamente , Diarrea/epidemiología , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Irinotecán , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/psicología , Masculino , Persona de Mediana Edad , Neutropenia/inducido químicamente , Neutropenia/epidemiología , Compuestos Organoplatinos/administración & dosificación , Cooperación del Paciente , Calidad de Vida , Análisis de Supervivencia , Taxoides/administración & dosificación , GemcitabinaRESUMEN
Given the prevalence of leishmaniasis and cancer, the co-existence of these two diseases may be merely coincidental. However, a number of epidemiological, experimental and laboratory studies suggest that an association between these two entities does exist. The aim of this review is to summarise the occurrence of leishmaniasis as an opportunistic infection associated with malignant disorders and to present the available literature potentially linking this infection with the development of cancerous lesions. We searched electronic databases and evaluated 37 studies involving 44 patients. Four different types of association between leishmaniasis and cancer were established: leishmaniasis mimicking a malignant disorder, such as lymphoma; leishmaniasis arising as a difficult to diagnose and treat infection among patients receiving chemotherapy for various malignant disorders; simultaneous diagnosis of leishmaniasis and a neoplastic disorder in the same tissue samples of immunocompromised patients; and direct involvement of Leishmania spp. in the pathogenesis/occurrence of malignant lesions, especially of the skin and mucous membranes. The main conclusion of this review is that leishmaniasis can directly or indirectly affect the presentation, diagnosis and course of various malignant disorders and it should be considered in the differential diagnosis of malignancies in geographic areas where it is endemic and/or in patients with travel history to these areas.
Asunto(s)
Leishmaniasis/complicaciones , Neoplasias/complicaciones , Carcinoma/complicaciones , Neoplasias Colorrectales/complicaciones , Femenino , Neoplasias de Cabeza y Cuello/complicaciones , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: The purpose of the present study was to evaluate the differences in the sequence of administration of 5-fluorouracil (5-FU)/leucovorin (LV) followed by irinotecan (CPT-11), or CPT-11 followed by 5-FU/LV in advanced colorectal cancer (ACC). PATIENTS AND METHODS: Chemotherapy-naïve patients with ACC were allocated to the following treatment groups: group A, a bolus of 20 mg/m(2) LV and 425 mg/m(2) 5-FU for 5 days until progression/relapse, and upon progression treatment with weekly CPT-11 (100 mg/m(2)), and group B, CPT-11 followed at progression/relapse by 5-FU/LV at the same doses and schedules as in group A. RESULTS: 120 patients were randomized to receive one of the two treatment sequences and their pretreatment characteristics were equally balanced between treatment arms. No statistically significant difference was found in the objective response rate to CPT-11 (p = 0.45); partial response (PR) was 23.3% for group A patients and 33.3% for group B. Following documented progression and second line treatment there was a significant difference between the response rate in group A (23.3%) and group B where no patients were found to respond to second-line treatment with 5-FU/LV (p = 0.024). The median overall survival was 42.0 weeks (range, 36.6-47.4 weeks) for group A and 32.0 weeks (range, 28.2-35.8 weeks) for group B. The median time to progression for patients in group A following first-line 5-FU/LV was 18 weeks (range, 10-36 weeks) and 12 weeks (range, 10-16 weeks) for group B following first-line CPT-11 (p = 0.0005). Toxicity, according to WHO, was similar between groups. CONCLUSIONS: Treating patients with CPT-11 upon progression to 5-FU/LV treatment seems to be superior to the opposite sequence. We used these treatments as sequential monotherapies (at progression/relapse), and the best results are gained when 5-FU/LV is followed by CPT-11 at disease progression or relapse.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Anciano , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Neoplasias Colorrectales/mortalidad , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Irinotecán , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Análisis Multivariante , Cooperación del PacienteRESUMEN
Spontaneous remission of acute myeloid leukemia (AML) in adults is a rare but well documented phenomenon. This study reports on a 64-year-old male patient with acute myelogenous leukemia (AML-M4, according to the French-American-British classification) that was developed on a background of chronic myelomonocytic leukemia (CMML) and then underwent remission after treatment with the gonadotropin-releasing hormone agonist (GnRH agonist) triptorelin for presumed prostate cancer. Remission persisted for at least 4 years before the patient was lost to follow-up. To the author' knowledge, this is the first report of remission in an AML-M4 case associated with hormone manipulation. Possible mechanisms of this phenomenon are discussed.
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Hormona Liberadora de Gonadotropina/agonistas , Leucemia Mielomonocítica Aguda/tratamiento farmacológico , Leucemia Mielomonocítica Aguda/patología , Leucemia Mielomonocítica Crónica/tratamiento farmacológico , Pamoato de Triptorelina/uso terapéutico , Estudios de Seguimiento , Humanos , Leucemia Mielomonocítica Aguda/diagnóstico , Leucemia Mielomonocítica Crónica/diagnóstico , Leucemia Mielomonocítica Crónica/patología , Masculino , Persona de Mediana Edad , Remisión Espontánea , Resultado del TratamientoRESUMEN
We undertook a prospective, nonrandomized study with the objective to evaluate the efficacy of salmon calcitonin (sCT) in controlling pain secondary to bone metastases. Our study population consisted of 45 cancer patients with bone metastases (26 men) with a mean age of 64 years (range, 48-70) who had completed chemotherapy, hormonal therapy and radiation therapy at least 30 days prior to enrollment in the study, and had intractable pain despite the use of common analgesics (acetaminophen, nonsteroidal anti-inflammatory agents, opioids) and bisphosphonates. The study medication was a 300-IU dose of sCT administered intravenously daily for 5 consecutive days and repeated every two weeks until no response was noticeable. The analgesic efficacy of sCT was evaluated by means of Huskisson's visual analogue scale and Keele's pain scale; the daily consumption of analgesic drugs and performance status were also monitored. None of the patients managed to completely discontinue the use of other analgesics, but 5 patients (11% of the total number) had an analgesic response that lasted 4 weeks and less than 5% of the patients continued to respond for 6 weeks. No significant side effects were observed. Our data show that intravenous calcitonin administered in a relatively high dose has a very limited therapeutic potential as an adjuvant analgesic for a short period of time in selected cancer patients with bone metastases.
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Analgésicos/uso terapéutico , Neoplasias Óseas/secundario , Huesos/metabolismo , Calcitonina/administración & dosificación , Calcitonina/uso terapéutico , Dolor Intratable/tratamiento farmacológico , Anciano , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/patología , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Cuidados Paliativos , Estudios Prospectivos , Factores de TiempoRESUMEN
Many investigations have focused on an optimal dosing schedule for paclitaxel since its regulatory approval. Paclitaxel is generally administered at a dose of 175 mg/m2 IV over 3 hours or 135-175 mg/m2 IV over 24 hours, every 3 weeks. The purpose of this study was to simplify the administration of paclitaxel to make it suitable and practical in the outpatient setting. Using this rationale, the duration of administration was decreased to 1 hour, with a minimized premedication regimen. Fifty-two patients scheduled to receive paclitaxel-based chemotherapy were entered into the study. Tumor types included non-small cell lung cancer, small cell lung cancer, breast cancer, head and neck cancer, and ovarian cancer. Twelve patients received paclitaxel 175 mg/m2 IV, and the remaining 40 patients received paclitaxel 225 mg/m2 IV. Premedication consisted of IV dexamethasone 20 mg over 5-10 minutes, given 30-60 minutes before infusion of paclitaxel,followed by IV dimethindene maleate 4 mg and IV ranitidine 50 mg over 30 minutes. Paclitaxel always was administered before other chemotherapeutic agents. Hypersensitivity reactions were recorded in 4 patients (7.7%) and were not influenced by age, gender, disease, dose schedule, or number of cycles of therapy; no serious hypersensitivity reactions were observed. The present study supports the efficacy and safety of a short premedication schedule; with further study, this schedule might become a standard premedication protocol prior to paclitaxel administration.
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Antineoplásicos Fitogénicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias/tratamiento farmacológico , Paclitaxel/administración & dosificación , Adulto , Anciano , Atención Ambulatoria , Antineoplásicos Fitogénicos/efectos adversos , Carboplatino/uso terapéutico , Intervalos de Confianza , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Epirrubicina/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Infusiones Intravenosas , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Neoplasias/patología , Premedicación , Estudios Prospectivos , Medición de Riesgo , Estadísticas no Paramétricas , Resultado del TratamientoRESUMEN
AIM: To determine the serum levels of c-reactive protein (CRP), transferrin (TRF), a2-macroglobulin (A2M), ceruloplasmin (CER), a1-acid glycoprotein (AAG), pre-albumin (P-ALB) and retinol-binding protein (RBP) in gastric carcinoma patients and to explore their possible correlation with underlying Helicobacter pylori (H pylori) infection. METHODS: We measured the serum levels of CRP, TRF, A2M, CER, AAG, P-ALB, and RBP in 153 preoperative patients (93 males; mean age: 63.1+/-11.3 years) with non-cardia gastric adenocarcinoma and 19 healthy subjects. RESULTS: The levels of CRP, CER, RBP, and AAG in cancer patients were significantly higher than those in healthy controls (P<0.0001), while no difference was found regarding the TRF, P-ALB, and A2M levels. Cancer patients with H pylori infection had significantly lower RBP values compared to non-infected ones (P<0.0001) and also higher values of CRP and AAG (P = 0.09 and P = 0.08, respectively). CONCLUSION: High serum levels of CRP, CER and AAG in cancer patients do not seem to be related to H pylori infection. Retinol-binding protein seems to discriminate between infected and non-infected patients with gastric carcinoma. Further studies are needed to explore if it is directly involved in the pathogenesis of the disease or is merely an epiphenomenon.
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Adenocarcinoma/complicaciones , Infecciones por Helicobacter/complicaciones , Helicobacter pylori , Neoplasias Gástricas/complicaciones , Proteínas de Fase Aguda/metabolismo , Adenocarcinoma/sangre , Adenocarcinoma/microbiología , Anciano , Biomarcadores de Tumor/sangre , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Unión al Retinol/metabolismo , Neoplasias Gástricas/sangre , Neoplasias Gástricas/microbiologíaRESUMEN
The aim of the present study was to evaluate the predictive value of cerebrospinal fluid (CSF) tumor marker levels in patients with breast cancer and carcinomatous meningitis. Serial CSF and serum tumor marker (CEA, CA-15.3, CA-125, and CA-19.9) measurements were performed in five patients with breast cancer developing carcinomatous meningitis in an attempt to correlate these with clinical outcome under treatment. CSF tumor marker levels correlated with response to treatment and outcome in each patient, and, despite achieving negative CSF cytology after therapy in two patients, it heralded disease progression. Given our findings, CSF tumor marker evaluation may provide a reliable means and surrogate end-points of monitoring response of carcinomatous meningitis to treatment. Therefore, large studies to assess the value of CSF tumor marker changes in carcinomatous meningitis are warranted.
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Biomarcadores de Tumor/líquido cefalorraquídeo , Neoplasias de la Mama/complicaciones , Neoplasias Meníngeas/terapia , Meningitis/terapia , Anciano , Neoplasias de la Mama/líquido cefalorraquídeo , Neoplasias de la Mama/terapia , Antígeno Carcinoembrionario/metabolismo , Progresión de la Enfermedad , Femenino , Humanos , Neoplasias Meníngeas/líquido cefalorraquídeo , Neoplasias Meníngeas/diagnóstico , Meningitis/líquido cefalorraquídeo , Meningitis/diagnóstico , Persona de Mediana Edad , Mucina-1/metabolismo , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
The activity of single-agent docetaxel in patients with platinum pretreated non-small cell lung cancer (NSCLC) has been established in two recent large randomized phase III trials, either against best supportive care or versus single-agent vinorelbine/ifosfamide. Moreover, single-agent gemcitabine has demonstrated significant activity and clinical benefit in platinum- and paclitaxel-pretreated advanced NSCLC. Combination regimens employing these two agents in various doses and schedules have recently been initiated. The gemcitabine/docetaxel combination with or without G-CSF support as salvage therapy of NSCLC pre-treated with platinum+/-paclitaxel-based regimens has been evaluated in four recently published phase II clinical studies and has been shown to represent a tolerable and active regimen in this setting, yielding a 10-33% response rate, thus, warranting randomized comparisons to single-agent gemcitabine or docetaxel, drugs currently recommended in second-line treatment of advanced NSCLC.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Neoplasias Pulmonares , Taxoides/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ensayos Clínicos como Asunto , Desoxicitidina/administración & dosificación , Docetaxel , Esquema de Medicación , Humanos , Terapia Recuperativa , Taxoides/administración & dosificación , Resultado del Tratamiento , GemcitabinaRESUMEN
PURPOSE: The present study aimed at evaluating the efficacy of Raltitrexed, a specific thymidilate synthase inhibitor, in patients with advanced colorectal cancer (ACC) in relapse (>8 weeks) after a prior response or disease stabilization to first-line chemotherapy combination with lrinotecan+5-Fluorouracil (5-FU)+Leucovorin (LV). METHODS: Twenty-five patients with metastatic ACC entered; 17 males/8 females, median age 61 (range: 47-70), median Karnovsky PS: 80 (70-90), and sites of metastases; liver: 21, lung: 4, lymph nodes: 7, peritoneal: 5 and a life expectancy of at least 3 months, were entered in the present pilot study. All patients had progressed after prior chemotherapy with lrinotecan+5-FU+LV. Raltitrexed was administered at a dose of 3 mg/m2 i.v. every 21 days. RESULTS: Three patients (12%) achieved a partial response (PR), 8 (32%) had stable disease (SD), and the remaining 14 (56%) developed progressive disease (PD). Median time-to-progression (TTP) was 5.5 months (range, 2-8.5), and median overall survival (OS) 8 months (range, 4.0-12.5). Toxicity was generally mild; it consisted mainly of myelosuppression; neutropenia grade 1-2: 52%-grade 3: 28%, and anemia grade 1-2 only: 36%. Mild mucositis grade 1-2 occurred in 13.5% of patients and was the principal non-hematologic toxicity. CONCLUSION: Response to treatment with Raltitrexed is limited in patients with ACC failing after an initial response or non-progression to the weekly lrinotecan+5-FU+LV combination. However, it appears that a limited number of patients with PR/SD may derive clinical benefit, but final proof would require a randomized study.
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Adenocarcinoma/secundario , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/secundario , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/secundario , Ganglios Linfáticos/patología , Neoplasias Peritoneales/secundario , Quinazolinas/uso terapéutico , Tiofenos/uso terapéutico , Adenocarcinoma/tratamiento farmacológico , Anciano , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Antimetabolitos Antineoplásicos/uso terapéutico , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Neoplasias Colorrectales/tratamiento farmacológico , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Irinotecán , Leucovorina/administración & dosificación , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Ganglios Linfáticos/efectos de los fármacos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasias Peritoneales/tratamiento farmacológico , Quinazolinas/administración & dosificación , Quinazolinas/efectos adversos , Terapia Recuperativa/efectos adversos , Terapia Recuperativa/métodos , Prevención Secundaria , Tiofenos/administración & dosificación , Tiofenos/efectos adversos , Resultado del TratamientoRESUMEN
Fifty-two consecutive patients with advanced colorectal cancer who developed persistent diarrhea following chemotherapy with 5-fluorouracil despite dose reduction were treated with amifostine 800, 500 or 150 mg/m(2). The administered dose of 5-fluorouracil was significantly greater during amifostine treatment. Amifostine 800 mg/m(2) was associated with complete elimination of diarrhea, but 76.3% of patients developed infusion-related hypotension. At a dose of 500 mg/m(2), diarrhea was significantly reduced and milder compared with baseline and the incidence of hypotension was 54.2%. At the lowest dose of amifostine, 17.1% of patients developed Grade 1 diarrhea, a significant reduction over baseline, and hypotension occurred in 25.2% of patients. Treatment with amifostine also improved mucositis but had no effect on the relatively mild nausea and vomiting due to 5-fluorouracil. In this study, amifostine reduced the incidence and severity of diarrhea associated with 5-fluorouracil in patients with advanced colorectal cancer, with acceptable efficacy at a reduced dose that offered better tolerability.
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Amifostina/administración & dosificación , Antimetabolitos Antineoplásicos/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Diarrea/prevención & control , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Anciano , Anciano de 80 o más Años , Diarrea/inducido químicamente , Diarrea/fisiopatología , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Masculino , Proyectos Piloto , Índice de Severidad de la EnfermedadRESUMEN
Uridine glucuronosyltransferase (UGT) gene polymorphisms have been linked to irinotecan toxicity. Our purpose was to study the association between UGT1A1*28, UGT1A7*2, and UGT1A7*3 polymorphisms and irinotecan toxicity in Greek patients receiving low-dose weekly irinotecan. Blood samples were collected for 46 patients. DNA was extracted and UGT1A1 promoter and UGT1A7 exon 1 genotyping was carried out. Laboratory tests and physical examination were performed on regular basis for the assessment of toxicity. UGT1A1*28 was significantly correlated with both haematologic and non-haematologic toxicity. Moreover, patients carrying UGT1A7 polymorphisms had significant incidence of toxicity. To conclude, UGT polymorphisms play a role in the toxicity of irinotecan, even if the drug is administered in low doses. The genotyping test may be a useful tool for the management of patients who are going to receive irinotecan.
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INTRODUCTION: In this case series and short review of the literature, we underline the impact of nephrectomy combined with sequential therapy based on cytokines, antiangiogenic factors, and mammalian target of rapamycin inhibitors along with metastasectomy on overall survival and quality of life in patients with metastatic clear cell renal carcinoma. CASE PRESENTATION: In the first of two cases reported here, a 53-year-old Caucasian man underwent a radical left nephrectomy for renal cell cancer and relapsed with a bone metastasis in his right humerus. He was treated with closed nailing and cytokine-based chemotherapy. For 5 years, the disease was stable and he had great improvement in quality of life. Subsequently, the disease relapsed in his lymph nodes, lung, and thorax soft tissue. He was then treated with antiangiogenic factors and mammalian target of rapamycin inhibitors. The disease progressed until September 2009, when he died of allergic shock during a blood transfusion, 9 years after the initial diagnosis of renal cell cancer.In the second case, a 54-year-old Caucasian man underwent a radical left nephrectomy for renal cell cancer. A year later, the disease progressed to his neck lymph nodes, and cytokine-based chemotherapy was initiated. While he was on cytokines, a solitary pulmonary nodule appeared and he underwent a metastasectomy. Nine months later, magnetic resonance imaging of his brain revealed a focal right occipitoparietal lesion, which was resected. After two years of active surveillance, the disease relapsed as a pulmonary metastasis and he was treated with an antiangiogenic factor. Further progressions presenting as enlarged axillary lymph nodes, chest soft tissue lesions, and thoracic spine bone metastases were sequentially observed. He then received a first-generation mammalian target of rapamycin inhibitor, an antiangiogenic factor, and later a second-generation mammalian target of rapamycin inhibitor and palliative radiotherapy. Ten years after the initial diagnosis of renal cell cancer, his disease is stable and he is on a third antiangiogenic factor and leads an active life. CONCLUSIONS: One multidisciplinary approach to patients with metastatic renal cell cancer combines nephrectomy, metastasectomy, and radiotherapy (when feasible) with medical therapy based on cytokines and targeted treatment employing agents inhibiting angiogenesis, other receptor tyrosine kinases, and mammalian target of rapamycin. This approach could prolong survival and improve quality of life.
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Platinum agents (cisplatin, carboplatin, and oxaliplatin) are a class of chemotherapy agents that have a broad spectrum of activity against several solid tumors. Toxicity to the peripheral nervous system is the major dose-limiting toxicity of at least some of the platinum drugs of clinical interest. Among the platinum compounds in clinical use, cisplatin is the most neurotoxic, inducing mainly sensory neuropathy of the upper and lower extremities. Carboplatin is generally considered to be less neurotoxic than cisplatin, but it is associated with a higher risk of neurological dysfunction if administered at high dose or in combination with agents considered to be neurotoxic. Oxaliplatin induces two types of peripheral neuropathy, acute and chronic. The incidence of oxaliplatin-induced neuropathy is related to various risk factors such as treatment schedule, cumulative dose, and time of infusion. To date, several neuroprotective agents including thiol compounds, vitamin E, various anticonvulsants, calcium-magnesium infusions, and other nonpharmacological strategies have been tested for their ability to prevent platinum-induced neurotoxicity with controversial results. Further studies on the prevention and treatment of neurotoxicity of platinum analogues are warranted.
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INTRODUCTION: This case report and short review discusses how long trastuzumab should be continued in metastatic breast cancer, the safety issues in case of pregnancy and the risk of relapse with trastuzumab cessation. CASE PRESENTATION: We present the case of a 34-year-old Caucasian woman with human epidermal growth factor receptor 2-positive metastatic breast cancer in the liver who achieved prolonged complete remission within six months of receiving trastuzumab (Herceptin) in combination with vinorelbine and gemcitabine. The patient remains in complete remission seven years later and continues to receive trastuzumab as maintenance therapy. CONCLUSION: Trastuzumab-based therapies have greatly improved the survival rates of patients with human epidermal growth factor receptor 2- positive metastatic breast cancer. Despite such improvements, the safety of trastuzumab administration during pregnancy is yet to be defined.
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PURPOSE: Human DNA topoisomerases I and II (topo-I and -II) are essential for vital cellular processes such as DNA replication, transcription, translation, recombination, and repair. In the present study, we correlate topo-I and -II expression and outcome after chemotherapy in primary and relapsed colorectal cancer. PATIENTS AND METHODS: Patients with colorectal cancer that had recurred, following surgery and adjuvant chemotherapy and underwent a second operation were included in the present study. All had undergone surgical resection of the primary tumor and received post-operatively 5-FU-based (5FU + Leucovorin, Mayo Clinic regimen) adjuvant chemotherapy. Tumor tissue was collected at the initial operation from the primary tumor and at the time of recurrence (during the second operation following chemotherapy). All tissue samples were analyzed for levels of expression of both topo-I and topo-IIa using standard three-step immunohistochemistry on paraffin sections. RESULTS: Forty patients were included. Levels of expression of topo-I and topo-II were higher in malignant cells from tumor recurrences compared to primary tumors (P = 0.0001 for both). There was a statistically significant positive relationship between patients age and levels of topo-I (P = 0.011) and topo-II (P = 0.011) expression. CONCLUSIONS: The study results reported here underscore the role of topoisomerase expression in colorectal cancer and suggest a potential role in tumor recurrence.