RESUMEN
PURPOSE AND METHODS: Although a high prevalence of adjustment disorders and anticipatory nausea secondary to adjuvant chemotherapy (CT) has been reported, little has been done to develop strategies to prevent these problems. A double-blind, placebo-controlled study was therefore designed to assess the usefulness of adding low-dose alprazolam (0.5 mg to 2 mg per day) to a psychologic support program including progressive relaxation training designed to prevent the aforementioned conditions. Fifty-seven women undergoing adjuvant CT for stage II primary breast cancer agreed to participate in the assessment, which was conducted at four time points: before starting CT, 6 weeks after CT, before the fourth CT, and after the fourth CT. The Hospital Anxiety and Depression Scale (HADS), Montgomery and Asberg Depression Rating Scale (MADRS), Hamilton Anxiety Scale (HAS), Revised Symptom Checklist (SCL-90-R), Morrow Assessment of Nausea and Emesis (MANE), and World Health Organization (WHO) grading of acute and subacute toxicities were used to compare the alprazolam (AA) and placebo (PA) arms of the study. RESULTS: At the second evaluation, the results showed a higher rate of anticipatory nausea (18% v 0%) in the PA compared with the AA arm (P = .038). These differences were no more significant at each of the further assessments. Significant differences were found for the intake of hypnotics at each assessment visit, with the rate of hypnotic users being significantly higher in the PA (19%) compared with the AA (0%) arm at the fourth assessment (P < .05). Anxiety and depression scores of self- and observer-report were similar in the two arms. A significant relationship was found between the development of anticipatory nausea and the self-report of anxiety and depression score measured by HADS at baseline. The average HADS total score at baseline was 15.33 (SD = 6.56) for patients who developed anticipatory nausea and 11.23 (SD = 6.67) for other patients. CONCLUSION: The adjunct of alprazolam to a psychologic support program delays the occurrence of anticipatory nausea and controls sleeping problems secondary to adjunct CT. Although studies are needed to improve the efficacy reported here, physicians may already consider the use of alprazolam for cancer patients undergoing CT.
Asunto(s)
Trastornos de Adaptación/prevención & control , Alprazolam/uso terapéutico , Quimioterapia Adyuvante/efectos adversos , Náusea/prevención & control , Vómito Precoz/prevención & control , Trastornos de Adaptación/inducido químicamente , Adulto , Anciano , Ansiedad/prevención & control , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante/psicología , Depresión/prevención & control , Método Doble Ciego , Femenino , Humanos , Persona de Mediana Edad , Análisis Multivariante , Náusea/inducido químicamente , Vómito Precoz/inducido químicamenteRESUMEN
PURPOSE: To evaluate the safety, tolerance, and hematologic effects of recombinant human interleukin-3 (IL-3) in patients with small-cell lung cancer (SCLC) before and following multiagent antineoplastic therapy in a placebo-controlled, randomized, double-blind study. PATIENTS AND METHODS: Twenty-eight patients (22 men and six women; median age, 60 years) with previously untreated SCLC entered the study. Patients were assigned to six groups of escalating-dose IL-3 ranging from 0.25 to 10 micrograms/kg/d administered by continuous infusion for 7 days, with one patient in each group receiving placebo. After a 1-week interval, the first of three cycles of carboplatin, etoposide (VP16), and epirubicin (CVE) given every 3 weeks was administered. The second cycle of CVE was followed by 7 days of IL-3 administered at the same daily dose as administered during the first infusion. RESULTS: The maximum-tolerated dose was not encountered in this study. Fever was the most frequently observed side effect. Before any chemotherapy, World Health Organization (WHO) grade II fever only appeared at doses > or = 2.5 micrograms/kg/d. Other side effects included rash, headache, and myalgia. During the first infusion of IL-3, before administration of chemotherapy, dose-dependent increases in peripheral-platelet counts (r = .613; P < .001) and neutrophil counts (r = .505; P = .007) were observed. Following the second cycle of CVE, recovery of peripheral platelet counts was faster as compared with the first cycle of CVE for patients treated with 7.5 and 10 micrograms/kg of IL-3 (P = .021). Chemotherapy postponements due to myelotoxicity were also less frequent following the second cycle of CVE as compared with the first for patients treated with > or = 2.5 micrograms/kg of IL-3 (P = .036). Compared with an age-matched historical group receiving identical chemotherapy (n = 191), administration of IL-3 did not modify either disease-free survival or overall patient survival rates. CONCLUSION: IL-3 is well tolerated at doses up to 10 micrograms/kg/d. In the absence of chemotherapy, biologic effects on both neutrophils and platelets were seen at doses > or = 2.5 micrograms/kg/d. IL-3 infusion following the second cycle of CVE appears to reduce chemotherapy-induced myelosuppression, but does not alter tumor response or patient survival rates.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Células Pequeñas/sangre , Hematopoyesis/efectos de los fármacos , Interleucina-3/farmacología , Neoplasias Pulmonares/sangre , Adulto , Anciano , Plaquetas/efectos de los fármacos , Carcinoma de Células Pequeñas/tratamiento farmacológico , Citocinas/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Interleucina-3/administración & dosificación , Interleucina-3/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Neutropenia/inducido químicamente , Neutropenia/prevención & control , Neutrófilos/efectos de los fármacos , Análisis de Supervivencia , Trombocitopenia/inducido químicamente , Trombocitopenia/prevención & control , Resultado del TratamientoRESUMEN
Eighty-three patients (median age, 56 years and Karnofsky performance status greater than or equal to 70) were treated with carboplatin (Carbo) and fluorouracil (5Fu) for stage III and IV head and neck squamous cell carcinoma (HNSCC). 5Fu (1 g/m2/d) was administered from day 1 to 4 by continuous infusion. Carbo was given on day 1 and, in order to evaluate its maximum-tolerated dose (MTD), the dose level was progressively increased from 250 mg/m2 to 450 mg/m2. The effectiveness of this association and its potential role in local control were also evaluated. Three patients received Carbo at a dose of 250 mg/m2, 13 received 300 mg/m2, one received 330 mg/m2, 12 received 350 mg/m2, six received 375 mg/m2, 26 received 400 mg/m2, 18 received 420 mg/m2, and four received 450 mg/m2. Two (13 of 83) or three courses (64 of 83), repeated every 4 weeks, were administered. The overall (primary tumor and node) response and complete response (CR) rates were 33% and 14%, respectively. For primary tumor, the response rate (RR) was 57% with 32% CR and 18% pathologic complete response (PCR); the RR was higher for patients with oropharyngeal tumor (76%, P = .037) and for patients treated with Carbo greater than or equal to 350 mg/m2 (65%, P = .02); the tumor size (T1 + T2 v T3 + T4) was a good prognostic factor for RR (90% v 46%, P = .001), CR (65% v 20%, P less than .001), and PCR (45% v 8%, P less than .001). For nodes, the RR was 33% with 11% CR. Grade 3-4 neutropenia and thrombocytopenia were experienced by 17% and 28% of the patients treated with 420 mg/m2 of Carbo and by 50% of the patients treated with 450 mg/m2. The MTD can be fixed at 420 mg/m2 and the proposed dose at 400 mg/m2. Thirty-eight patients were treated with surgery plus radiotherapy, 33 with radiotherapy alone, and seven with surgery alone. The median follow-up is 12 months. The 18-month disease-free survival (DFS) is 78% for overall complete responders and 39% for the others (P = .04). There is no primary tumor recurrence among the 12 patients with a primary tumor PCR treated by radiotherapy alone for tumor control (median follow-up, 17.3 months). The association of Carbo-5Fu is a safe induction chemotherapy regimen for HNSCC. The proposed dose of Carbo for future treatment is 400 mg/m2.(ABSTRACT TRUNCATED AT 400 WORDS)
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/patología , Recurrencia Local de Neoplasia/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Carcinoma de Células Escamosas/mortalidad , Terapia Combinada , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Evaluación de Medicamentos , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Inducción de Remisión , Tasa de SupervivenciaRESUMEN
A multicentric randomized prospective trial was conducted to test whether late intensification chemotherapy would increase the remission rate, the relapse-free survival, and the survival of small-cell lung cancer patients responding to induction chemotherapy. Autologous bone marrow transplantation was used as support to reduce the duration of the aplasia induced by very high-dose chemotherapy. As induction chemotherapy, 101 patients received, during a period of 5 months, a total dosage of 120 mg/m2 methotrexate, 4.5 mg/m2 vincristine, 1,800 mg/m2 cyclophosphamide, 180 mg/m2 doxorubicin, 160 mg/m2 cisplatin, 750 mg/m2 VP-16-213, and 30 Gy prophylactic cranial irradiation. Forty-five patients, selected for their sensitivity to this induction treatment, were randomized to a last cycle of chemotherapy that combined cyclophosphamide, BCNU, and VP-16-213 either at a conventional dosage of 750 mg/m2 intravenously (IV), 60 mg/m2 IV, and 600 mg/m2 orally or alternatively at a very high dosage of 6 g/m2 IV, 300 mg/m2 IV, and 500 mg/m2 IV, respectively. In the late intensification group, the complete remission rate increased from 39% before randomization to 79% after high-dose chemotherapy. Median relapse-free survivals after randomization for intensified and control chemotherapy groups were 28 and 10 weeks, respectively (P = .002). Median overall survival after induction therapy was 68 weeks for the intensified group compared with 55 weeks for the conventional therapy group (P = .13). Four patients died during intensification. Patients in both groups relapsed at the primary site. It can thus be concluded that late intensification chemotherapy for sensitive small-cell lung cancer increases the complete remission rate and resulted in a statistically significant increase in the relapse-free survival. However, since relapse occurred at the primary site and toxicity was high, overall survival was not significantly improved.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea , Carcinoma de Células Pequeñas/terapia , Neoplasias Pulmonares/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Células Pequeñas/tratamiento farmacológico , Carcinoma de Células Pequeñas/mortalidad , Ensayos Clínicos como Asunto , Terapia Combinada , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Masculino , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estudios Prospectivos/efectos adversos , Distribución Aleatoria , Trasplante Autólogo , Vincristina/administración & dosificaciónRESUMEN
PURPOSE: To compare a full-dose epirubicin-cyclophosphamide (HEC) regimen with classical cyclophosphamide, methotrexate, and fluorouracil (CMF) therapy and with a moderate-dose epirubicin-cyclophosphamide regimen (EC) in the adjuvant therapy of node-positive breast cancer. PATIENTS AND METHODS: Node-positive breast cancer patients who were aged 70 years or younger were randomly allocated to one of the following treatments: CMF for six cycles (oral cyclophosphamide); EC for eight cycles (epirubicin 60 mg/m(2), cyclophosphamide 500 mg/m(2); day 1 every 3 weeks); and HEC for eight cycles (epirubicin 100 mg/m(2), cyclophosphamide 830 mg/m(2); day 1 every 3 weeks). RESULTS: Two hundred fifty-five, 267, and 255 eligible patients were treated with CMF, EC, and HEC, respectively. Patient characteristics were well balanced among the three arms. One and three cases of congestive heart failure were reported in the EC and HEC arms, respectively. Three cases of acute myeloid leukemia were reported in the HEC arm. After 4 years of median follow-up, no statistically significant differences were observed between HEC and CMF (event-free survival [EFS]: hazards ratio [HR] = 0.96, 95% confidence interval [CI], 0.70 to 1.31, P =.80; distant-EFS: HR = 0.97, 95% CI, 0.70 to 1.34, P =.87; overall survival [OS]: HR = 0.97, 95% CI, 0.65 to 1.44, P =.87). HEC is more effective than EC (EFS: HR = 0.73, 95% CI, 0.54 to 0.99, P =.04; distant-EFS: HR = 0.75, 95% CI, 0.55 to 1.02, P =.06; OS HR = 0.69, 95% CI, 0.47 to 1.00, P =.05). CONCLUSION: This three-arm study does not show an advantage in favor of an adequately dosed epirubicin-based regimen over classical CMF in the adjuvant therapy of node-positive pre- and postmenopausal women with breast cancer. Moreover, this study confirms that there is a dose-response curve for epirubicin in breast cancer adjuvant therapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bélgica/epidemiología , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Quimioterapia Adyuvante/métodos , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Epirrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Metotrexato/administración & dosificación , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estadísticas no Paramétricas , Tasa de SupervivenciaRESUMEN
Forty-six previously untreated patients with advanced breast cancer were eligible for the present randomised phase I study. It aimed to evaluate the toxicity and activity of a therapeutic sequence with epirubicin on day 1 followed by paclitaxel on day 2 (sequence A) or the reverse sequence, ie., paclitaxel on day 1 followed by epirubicin on day 2 (sequence B). The starting doses of epirubicin and paclitaxel, administered either according to sequence A or B, (level 1 cohort) were 90 mg/m2 and 175 mg/m2, respectively. Per cohort of 3 patients, the dose of paclitaxel was increased by 25 mg/m2 (levels 2 and 4) and of epirubicin by 10 mg/m2 (levels 3 and 5). Treatment was repeated with 3-week intervals. The maximal tolerated dose (MTD) was achieved at level 1 in sequence B (paclitaxel first) and level 3 (epirubicin 100 mg/m2 followed by paclitaxel 200 mg m2) in sequence A. Dose limiting toxicity (DLT) was neutropenia (+/- febrile) in both sequences. Cardiac events occurred in 28% of the patients; significant decrease in left ventricular ejection function (LVEF) was observed in 8/33 and in 2/13 patients in sequence A and B, respectively. This was associated with 5 and 1 cardiac heart failure (CHF), respectively. In 43 evaluable patients, 10 CR and 25 PR were observed (overall response rate 81%). In the 20 patients with locally advanced disease (LABC), the respective numbers were 7 CR and 11 PR; in the 23 metastatic (MBC) patients, 3 CR and 14 PR were recorded. The median survival of the both groups was not reached at 33 + months. In conclusion , the combination of epirubicin and paclitaxel has significant activity in breast cancer. The recommended sequence of both drugs in combination therapy, mainly to avoid neutropenia, is epirubicin day 1 followed by paclitaxel on day 2. Cardiac toxicity remains problematic in either sequence of administration.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Epirrubicina/administración & dosificación , Paclitaxel/administración & dosificación , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Esquema de Medicación , Epirrubicina/efectos adversos , Femenino , Corazón/efectos de los fármacos , Cardiopatías/inducido químicamente , Sistema Hematopoyético/efectos de los fármacos , Humanos , Dosis Máxima Tolerada , Persona de Mediana Edad , Neutropenia/inducido químicamente , Paclitaxel/efectos adversos , Volumen Sistólico/efectos de los fármacosRESUMEN
The purpose of this communication was to explore which situations in radiotherapy might benefit from concomitant administration of haematopoietic growth factors (HGF). Only large-field radiotherapy is likely to induce bone marrow depression, such as irradiation of Hodgkin's disease. Therefore, we studied 122 patients irradiated for Hodgkin's disease, looking at peripheral blood cell count before, during and after the treatment. One hundred and four treatments were preceded by chemotherapy (MOPP and/or ABVD) and the radiation dose was between 36 and 44 Gy in 2 Gy per fraction sessions. Severe leucopenia (grade III WHO) was very uncommon and justified treatment interruption only twice. In both cases, it was paired with thrombocytopenia. No infection developed. It is concluded that when radiotherapy is used alone, prophylactic use of HGFs does not seem justified. This, of course, does not apply to radiochemotherapy combinations, although thorough investigations in this field are still awaited.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Enfermedad de Hodgkin/radioterapia , Leucopenia/prevención & control , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Terapia Combinada , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Leucopenia/etiología , Persona de Mediana Edad , Radioterapia/efectos adversos , Estudios RetrospectivosRESUMEN
BACKGROUND AND PURPOSE: To determine the distribution of set-up errors for patients treated with and without two rigid partial immobilisation devices for pelvic malignancies. MATERIALS AND METHODS: 30 patients receiving pelvic irradiation with a four field technique underwent a total of 524 portal films. The patients are divided into 3 cohorts of 10 patients. The first cohort is treated on a standard treatment couch without immobilisation device (NI); the second and third cohorts are treated with a custom-made immobilisation device used in an attempt to improve set-up accuracy: an Alpha-Cradle mattress (AM) or an Orfit cast (OC). Set-up deviations are analysed in the X, Y, Z directions of a fixed coordinate system, corresponding to the lateral, cranio-caudal and antero-posterior direction, respectively. RESULTS: Considering the percentage of discrepancies < or = 5 mm between the simulation films and the portal films as a measure of set-up accuracy, immobilisation devices seem to increase accuracy: 88.5% (X) 79% (Y) and 100% (Z) with AM; 84% (X-Y), 97.5% (Z) with OC and only 76.5% (X), 40% (Y) and 65.5% (Z) for NI. The distribution of the systematic set-up errors for the three patient cohorts, defined as the mean patient displacement for the treatment course, had a mean and a standard deviation of (0.7 +/- 2.7) mm in the X-axis, (-5.5 +/- 2.6) mm in the Y-axis and (-0.9 +/- 2.2) mm in the Z-axis when no immobilisation is added; (0.8 +/- 1.7) mm, (-2 +/- 2.7) mm and (0.3 +/- 0.4) mm for the Alpha-Cradle group; (0.3 +/- 1.4) mm, (0.5 +/- 1.1) mm and (0.5 +/- 0.6) mm for the Orfit cast group. The distribution of random errors about the mean approximated a normal distribution and the standard deviations are 4.4 mm (X), 4.2 mm (Y) and 4.8 mm (Z) for NI; 3.3, 3.5 and 2.5 mm for the AM; 3.4, 3.3 and 2.7 mm for the OC. CONCLUSIONS: The two rigid immobilisation devices improve the reproducibility of a given pelvic field but there is a small benefit comparative to the cost and the cumbersome place of the devices.
Asunto(s)
Inmovilización , Neoplasias Pélvicas/radioterapia , Radioterapia/instrumentación , Femenino , Humanos , Masculino , Errores Médicos/prevención & control , Postura , Reproducibilidad de los Resultados , Tecnología RadiológicaRESUMEN
BACKGROUND: Increasing the radiation dose to prostatic adenocarcinoma has provided higher local control rates. A total of 80 Gy seem necessary to achieve this goal but patient set-up and prostate motion remain difficult problems to solve in conformal radiotherapy. Brachytherapy which overcomes these points could be an alternative way to external beam boost fields. We wanted to transpose the irradiation models largely used in cervix cancer treatment combining external beam radiotherapy and low dose rate brachytherapy. MATERIALS AND METHODS: In 71 patients with 19.5 and 13 ng/ml mean and median PSA levels, respectively, a dose escalation from 74 to 85 Gy was performed in four groups. RESULTS: Shifting from intraoperative placement of sources vectors (Group I) to positioning under ultrasound controls (groups II-IV), improving the implantation shape and optimizing radiation delivery to urethral bed have reduced the total dose to rectal wall under 65 Gy and to urethra under 100 Gy. Rectal/prostate dose ratio was lowered from 0.7 (Groups I-II) to 0.58 (Groups III-IV) while avoiding problems resulting from pelvic bone arch interference, prostate volume or seminal vesicles location. The mean and median follow-up periods are 28 and 18 months. In Groups III and IV 85% of patients without hormonotherapy treated with 80-85 Gy normalized PSA under 1 ng/ml within 6 months. No severe late effect has been noted for patients implanted under echographic control. CONCLUSIONS: The method described allows to deliver 85 Gy. Longer follow-up is however needed but the levels of dose delivered are not expected to induce prohibitive side effects.
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Adenocarcinoma/radioterapia , Braquiterapia , Radioisótopos de Iridio/uso terapéutico , Neoplasias de la Próstata/radioterapia , Radiofármacos/uso terapéutico , Anciano , Análisis de Varianza , Antineoplásicos Hormonales/uso terapéutico , Braquiterapia/efectos adversos , Braquiterapia/instrumentación , Quimioterapia Adyuvante , Distribución de Chi-Cuadrado , Estudios de Factibilidad , Estudios de Seguimiento , Humanos , Cuidados Intraoperatorios , Radioisótopos de Iridio/administración & dosificación , Radioisótopos de Iridio/efectos adversos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/prevención & control , Huesos Pélvicos/efectos de la radiación , Próstata/efectos de la radiación , Antígeno Prostático Específico/análisis , Radiofármacos/administración & dosificación , Radiofármacos/efectos adversos , Dosificación Radioterapéutica , Radioterapia Conformacional , Recto/efectos de la radiación , Vesículas Seminales/efectos de la radiación , Ultrasonografía Intervencional , Uretra/efectos de la radiaciónRESUMEN
Seventy autologous peripheral blood stem cell transplants (APBSCT) performed in 61 cancer patients were retrospectively analyzed. Patients were heterogenous with regard to malignancy, conditioning regimens and use of growth factors after transplantation. Six patients developed a non-infectious fever, fluid retention and pulmonary interstitial infiltrates during the early phase of neutrophil recovery. Diarrhea was observed in four of these patients and cutaneous rash in three. The clinical condition improved spontaneously in one patient, and within 48 h after steroid therapy in four. One patient died from multiple organ failure. Age, sex (all patients were female; P = 0.07), and time to platelet recovery did not distinguish the six courses complicated by the hypothetical engraftment syndrome (ES) from the other 64 courses taken as controls. However, neutrophil recovery > 0.5 x 10(9)/l occurred earlier (P = 0.01), and the neutrophil count increment during the early phase of recovery was steeper in ES patients (P = 0.003). ES was also associated with infusion of a high number of CD34+ progenitors (P = 0.03) and conditioning with busulfan (P = 0.03). Although all ES patients received G-CSF after transplantation, an association of ES with G-CSF use could not be demonstrated, possibly because of the small number of courses not supported by G-CSF. However, in one patient, ES did not recur after a second transplant unsupported by growth factors. Our study supports the idea of an engraftment syndrome associated with an early and steep neutrophil recovery after APBSCT.
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Supervivencia de Injerto , Trasplante de Células Madre Hematopoyéticas , Activación Neutrófila , Neutrófilos/patología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Síndrome , Trasplante AutólogoRESUMEN
Relative biological effectiveness (RBE) and oxygen enhancement ratio (OER) values of different neutron beams produced at the variable energy cyclotron "Cyclone" of Louvain-la-Neuve (Belgium) were determined. The neutrons were obtained by bombarding a beryllium target with 34-, 45-, 65-, or 75-MeV protons or with 50-MeV deuterons. The biological system was growth inhibition in Vicia faba bean roots. Taking the p(65) + Be neutron beam as a reference, RBE values were found equal to 1.36 +/- 0.2, 1.20 +/- 0.1, 1.00 (ref), 0.98 +/- 0.1, and 1.18 +/- 0.1, respectively; the doses corresponding to 50% growth inhibition were 0.39, 0.44, 0.53, 0.54, and 0.45 Gy. For the same beams, OER values were found equal to 1.55 +/- 0.1, 1.38 +/- 0.1, 1.29 +/- 0.1, 1.41 +/- 0.1, and 1.60 +/- 0.2, respectively.
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Neutrones , Aceleradores de Partículas , Crecimiento/efectos de la radiación , Modelos Biológicos , Oxígeno/fisiología , Plantas/efectos de la radiación , Efectividad Biológica RelativaRESUMEN
The RBE of p(75) + Be neutrons relative to d(50) + Be neutrons has been determined for chromosome aberrations induced in Allium cepa (onion) roots. Two biological criteria were selected: the average number of aberrations (mainly fragments) per cell in anaphase and telophase, and the percentage of aberration-free cells. The influence of sampling time (3 to 7 h incubation) between irradiation and fixation was investigated systematically. This factor did not significantly influence the results. The RBE values of p(75) + Be neutrons compared to those of d(50) + Be neutrons were 0.85 (0.79-0.91) and 0.87 (0.80-0.95) for the first and the second criteria, respectively. In previous experiments for the same beams, we found an RBE of 0.90 (0.86-0.94) for survival of V79 cells (D0 ratio), 0.96 (0.93-0.99) for the intestinal crypt cell system, and 0.83 (0.70-0.96) for Vicia faba growth delay.
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Aberraciones Cromosómicas , Neutrones , Allium/efectos de la radiación , Berilio , Deuterio , Protones , Genética de Radiación , Efectividad Biológica RelativaRESUMEN
In an early phase II trial combining gemcitabine (dFdC) and radiotherapy for lung carcinomas, severe pulmonary toxicity was observed. In this framework, the objective of this study was to investigate the effect of dFdC on the tolerance of the lungs of C3H mice to single-dose irradiation. The thoraxes of C3H mice were irradiated with a graded single dose of 8 MV photons; dFdC (150 mg/kg) or saline (control animals) was administered i.p. 3 or 48 h prior to irradiation. Lung tolerance was assessed by the LD50 at 7-180 days after irradiation. For irradiation alone, the LD50 reached 14.45 Gy (95% CI 13.33-15.66 Gy). With a 3-h interval between administration of dFdC and irradiation, the LD50 reached 13.29 (95% CI 12.26-14.44 Gy); the corresponding value with a 48-h interval reached 13.01 Gy (95% CI 11.92-14.20 Gy). Our data also suggested a possible effect of dFdC on radiation-induced esophageal toxicity. dFdC has a minimal effect on lung tolerance after single-dose irradiation. However, a proper phase I-II trial should be designed before any routine use of combined dFdC and radiotherapy in the thoracic region.
Asunto(s)
Antimetabolitos Antineoplásicos/farmacología , Desoxicitidina/análogos & derivados , Pulmón/efectos de la radiación , Tolerancia a Radiación/efectos de los fármacos , Animales , Desoxicitidina/farmacología , Relación Dosis-Respuesta en la Radiación , Masculino , Ratones , Ratones Endogámicos C3H , GemcitabinaRESUMEN
The lung tolerance in mice after single and fractionated irradiations with p(45)+Be and p(65)+Be neutrons produced at the isochronous cyclotron "CYCLONE" of Louvain-la-Neuve (Belgium) was studied. Cobalt-60 gamma rays were used for control irradiations. The end point was the dose which was lethal to 50% of the mice by 180 days (LD50/180). On a log-log plot, the slope (+/- SE) of the relationship between total isoeffect dose and fraction number decreases from 0.34 +/- 0.01 for gamma rays to 0.19 +/- 0.01 for p(65)+Be and 0.12 +/- 0.01 for p(45)+Be neutrons. The data have been analyzed using the linear-quadratic (LQ) model. The alpha/beta ratio (+95% confidence interval) increases from 5.3 (4.3-6.4) for gamma rays to 20.7 (16.7-24.9) for p(65)+Be and 37.9 (25.8-65.8) for p(45)+Be. The RBEs of neutrons relative to gamma rays were estimated from the LQ parameters, to 1.15 and 1.19 for a dose of 14 Gy gamma rays and 2.02 and 2.47 for a dose of 2 Gy gamma rays for p(65)+Be and p(45)+Be neutrons, respectively. The neutron RBE of the p(45)+Be relative to the p(65)+Be calculated from the ratio of their respective RBEs relative to gamma rays reaches 1.03 and 1.23 for doses of 14 and 2 Gy gamma-ray equivalent, respectively. These data are compared with other published data on lung tolerance after irradiation with lower-energy neutrons and with data obtained previously in our laboratory on mouse jejunum and Vicia faba.
Asunto(s)
Neutrones Rápidos , Pulmón/efectos de la radiación , Tolerancia a Radiación , Animales , Berilio , Ciclotrones , Femenino , Ratones , Dosis de Radiación , Efectividad Biológica RelativaRESUMEN
In an ongoing phase II trial conducted in advanced breast cancer, we tested a therapy schedule consisting of continuous, 24-h infusion of 5 g/m2 ifosfamide (IFO) in 3 1 dextrose saline with mesna (MSN), repeated every 3 weeks until disease progression. Since September 1988, 16 heavily pretreated patients with advanced disease (11 with visceral lesions) considered refractory to standard chemotherapy (regimens always including cyclophosphamide) have been included. Objective partial remissions were observed in two cases (one in liver and one in soft-tissue and pleural lesions), and disease stabilization for at least 3 months occurred in four cases. No treatment-related death was recorded and tolerance was judged to be excellent (six cases) or acceptable in all instances. The haematological toxicity consisted mainly of transient leucopenia (nadirs evaluated by WHO scale as grade 3 in 43% and grade 4 in 29%), sometimes associated with thrombocytopenia (grade 3 in 7% and grade 4 in 7%). Other side effects included nausea and/or vomiting (grade 3-4 in 33%); worsening of preexisting alopecia (five cases); haemorrhagic cystitis (one case); mild, transient somnolence (two cases); and moderate fluid retention (two cases). We concluded that infusion of 5 g/m2 IFO over 24 h with MSN rescue might represent an acceptable second- or third-line salvage regimen. Close monitoring of haematological and renal function parameters is recommended. A larger number of patients will be treated in a continuation of this study to evaluate the true response rate within narrower confidence limits.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Ifosfamida/administración & dosificación , Mercaptoetanol/análogos & derivados , Mesna/administración & dosificación , Adulto , Femenino , Humanos , Ifosfamida/efectos adversos , Persona de Mediana EdadRESUMEN
Asbestos-associated malignancies are one of the major industrial hazards of recent decades and will continue to be so until beyond the end of the century. It has been estimated that, in the United States alone, there will be 131,200 cancer deaths as a result of asbestos exposure. At present the early lesions are detected radiologically, by which time intervention is no longer effective. The aim of this study was to test the value of a battery of serum biomarkers in the early detection of malignancy and in distinguishing between the early stages of mesothelioma and bronchogenic carcinoma. Many of the biomarkers had no discriminating value but on the basis of four such markers (namely TPA, CEA, HA and ferritin) it has been possible to distinguish between the late stages of the two malignancies and asbestosis. The results are discussed in terms of their possible application to the detection of early pre-malignant lesions in a screened population of asbestos-exposed persons, with the aim of attempting to prevent cancer death in such early detected cases.
Asunto(s)
Amianto/efectos adversos , Biomarcadores de Tumor/sangre , Carcinoma Broncogénico/sangre , Carcinoma Broncogénico/prevención & control , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/prevención & control , Mesotelioma/sangre , Mesotelioma/prevención & control , Enfermedades Profesionales/sangre , Enfermedades Profesionales/prevención & control , Exposición Profesional , Antígenos de Neoplasias/sangre , Antígenos de Carbohidratos Asociados a Tumores/sangre , Asbestosis/sangre , Antígeno Carcinoembrionario/sangre , Ferritinas/sangre , Humanos , Ácido Hialurónico/sangre , Péptidos/sangre , Fosfopiruvato Hidratasa/sangre , Antígeno Polipéptido de TejidoRESUMEN
In the first part of this study we have shown how the serum levels of four selected tumour markers, namely tissue polypeptide antigen (TPA), carcino-embryonic antigen (CEA), hyaluronic acid (HA) and ferritin, display patterns characteristic of mesothelioma (M) or bronchogenic carcinoma (BC) in asbestos-exposed workers, and we hypothesize that the differences in marker patterns correspond to differences in carcinogenesis mechanisms. In a preliminary study, we found these specific marker patterns in 5/19 exposed workers of whom only one demonstrated any radiological signs of disease. Thus these specific marker patterns may be early events, occurring long (possibly years) before the classical radiological signs of exposure to asbestos. Accordingly they afford an optimal opportunity for prevention which should be adapted to the carcinogenesis mechanism as it is revealed by the marker pattern; it is aimed at antagonizing free radical carcinogenesis in all persons with TPA levels in excess of 100 U/l or Ferritin in excess of 400 ng/ml, and at inhibiting chemical carcinogenesis in those having elevated CEA levels (over 3 ng/ml). The mechanisms involved in these inhibitory processes are described and discussed, as well as the practical implementations that proceed from them. A prevention trial is now being started among 300 active and retired workers of an asbestos-cement works in northern France; the design of the study is presented. This prevention programme should be maintained over many years and holds a strong potential for reducing the untoward effects of exposure to asbestos.
Asunto(s)
Amianto/efectos adversos , Biomarcadores de Tumor/sangre , Carcinoma Broncogénico/prevención & control , Neoplasias Pulmonares/prevención & control , Mesotelioma/prevención & control , Enfermedades Profesionales/prevención & control , Exposición Profesional , Acetilcisteína/uso terapéutico , Antígenos de Neoplasias/sangre , Ácido Ascórbico/uso terapéutico , Antígeno Carcinoembrionario/sangre , Carcinoma Broncogénico/sangre , Carotenoides/sangre , Carotenoides/uso terapéutico , Estudios de Cohortes , Ferritinas/sangre , Humanos , Ácido Hialurónico/sangre , Estudios Longitudinales , Neoplasias Pulmonares/sangre , Masculino , Mesotelioma/sangre , Persona de Mediana Edad , Enfermedades Profesionales/sangre , Péptidos/sangre , Riboflavina/uso terapéutico , Selenio/sangre , Selenio/uso terapéutico , Antígeno Polipéptido de Tejido , Vitamina A/sangre , Vitamina E/sangre , Vitamina E/uso terapéutico , beta CarotenoRESUMEN
366 patients fully resected from a Dukes B2 or C colorectal cancer were randomised to receive 6 courses of systemic chemotherapy comprising either 5-fluorouracil (5 FU) alone (arm A: 450 mg/m2/day-5/21 days) or combined folinic acid (FOL) and 5 FU (arm B: respectively 200 mg/m2 racemic form or 100 mg/m2-l-form and 370 mg/m2/day-5/21 days). 173 patients had also been initially randomised to receive one course of intraportal chemotherapy just after surgery or no portal treatment. Oral levamisole (150 mg/day; 3 days every other week) was given to all patients for one year. A significantly higher incidence of leuco-granulocytopenia was observed in the arm A (5 FU alone) inducing more frequent dose delays and adaptations as well as levamisole's withdrawal. Then dose-intensities and dose-intensity products were lower in this arm but the dose intensity expressed in mg/m2/week remained higher (631 +/- 107 vs 557 +/- 99; p < 0.001). The median follow-up in the study was 4.5 years. Relapse free (RFS) and overall survivals (OAS) were prolonged in the 5 FU alone group peculiarly in those patients who had not been randomised for portal treatment. Curves diverged progressively with longer follows-up (at 8 years; RFS in arm A: 67-71% vs 59-53% in arm B; OAS in arm A: 72-74% vs 56-46% in arm B). Patients suffering from a colon or a Dukes C cancer benefited the most from the treatment with 5 FU alone. The results are discussed in the light of other recent adjuvant trials. Well dosed 5 FU over a short period of time without folinic acid may be a valuable and inexpensive adjuvant treatment for colorectal cancer. Levamisole may no longer be recommended in this setting.
Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Fluorouracilo/uso terapéutico , Neoplasias del Recto/tratamiento farmacológico , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/uso terapéutico , Adulto , Anciano , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Quimioterapia Adyuvante , Distribución de Chi-Cuadrado , Neoplasias del Colon/mortalidad , Neoplasias del Colon/patología , Neoplasias del Colon/cirugía , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Estudios de Seguimiento , Humanos , Infusiones Intravenosas , Inyecciones Intravenosas , Leucovorina/administración & dosificación , Leucovorina/uso terapéutico , Levamisol/administración & dosificación , Levamisol/uso terapéutico , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Sistema Porta , Radioterapia Adyuvante , Neoplasias del Recto/mortalidad , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Tasa de SupervivenciaRESUMEN
In a prospective randomized trial comparing CMF to CMF + HD-MPA for primary node positive breast cancer patients, the authors evidenced clear improvement of hematological tolerance (especially of WBC - granulocytes counts) to chemotherapy in the group receiving also hormonotherapy. The design of the trial allowed to give the patients overall high doses of CMF therapy in both arms; in the group receiving HD-MPA significantly higher doses of CMF could be administered (96.3-97.8% for CMF + HD-MPA treated patients vs 89.7-91.1% for CMF alone treated patients). The menopausal status did not influence the results.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Medroxiprogesterona/análogos & derivados , Adulto , Anciano , Ensayos Clínicos como Asunto , Ciclofosfamida/uso terapéutico , Interacciones Farmacológicas , Femenino , Fluorouracilo/uso terapéutico , Hemoglobinas/análisis , Humanos , Recuento de Leucocitos , Medroxiprogesterona/uso terapéutico , Acetato de Medroxiprogesterona , Metotrexato/uso terapéutico , Persona de Mediana Edad , Recuento de Plaquetas , Distribución AleatoriaRESUMEN
Ninety postmenopausal women with advanced breast cancer were randomly assigned to be treated with HD-MPA administered either by oral route (daily dose 900 mg) or by intramuscular injections (1 g IM daily X 5 q w during 4 consecutive weeks followed by maintenance with 1 g twice weekly). Among 78 evaluable cases, most heavily pretreated, remissions, lasting for a median duration of 11 months, were more frequent on oral (8/37 = 22%) than on IM therapy (5/41 = 12%). In both arms, high estrogen receptor levels and various clinical factors were associated with higher response rates i.e., age greater than 60, Karnofsky greater than 70, light prior systemic treatment. Side-effects, consisting mainly of weight gain, hypertension and tremor occurred with equal frequency on oral or IM treatment. Five patients complained of pain at the sites of IM injections. Thus, we recommended that, whenever possible, the oral route should be preferred. During the same study, in 20 patients (11 on oral and 9 on IM therapy), blood was drawn at 0, 30, and 60 days of treatment for the assessment of MPA and hormone levels. In both arms, at 60 days, comparable levels of circulating MPA were obtained, with a very significant drop of cortisol, androstenedione, and estrone. These endocrine results, together with our clinical data, indicate that HD-MPA therapy is active on estrogen-dependent tumors with the same specificity as that of other modalities aiming to suppress the adrenal function. Its antineoplastic action in humans could be ascribed at least in part to its suppressive action on the adrenals, resulting in a severe estrogenic deprivation in postmenopausal women.