RESUMEN
PURPOSE: The Veneto Region implemented a novel integrated home-based palliative cancer care (HPCC) program embedded in primary care. We examined the impact of timing and intensity of this program on the quality of end-of-life (EOL) care. METHODS: We selected adult cancer patients died in the Veneto Region between March and December 2013, excluding those died from haematological malignancies as well as the very elderly (85+ years). We retrieved the claim-based data on hospitalization and homecare visits, and defined two observation windows: 90 to 16 days before death to examine intensity of HPCC exposure, and the last 15 days of life to examine EOL outcomes, including hospital death, any hospital stay for medical reasons and hospital stay ≥7 days for medical reasons. Multivariate analysis was conducted using a Poisson model. RESULTS: Among the 2211 adults who died of solid tumours and received 1+ homecare visits during the exposure period, 1077 (48.7%), 552 (25.0%) and 582 (26.3%) had 0.1-1.9, 2-3.9 and 4+ homecare visits/week, respectively. The median duration between an HPCC home visit and death was 92 days (IQR 42-257 days). Hospital death occurred in 856 (38.7%) patients, while 1087 (49.2%) and 556 (25.1%) had a hospital stay and a hospital stay ≥7 days during the exposure period, respectively. In the multivariate analysis, a greater intensity of integrated HPCC (4+ visits/week) was significantly associated with a lower risk of hospital death (relative risk [RR] = 0.67, 0.59-0.76), any hospital stay (RR = 0.69, 0.62-0.77) and hospital stay ≥7 days for medical reasons (RR = 0.59, 0.49-0.71). A late activation (≤30 days before death) of HPCC was also associated with increased both hospital stay (RR = 1.26, 0.11-1.42) and hospital stay ≥7 days (RR = 1.25, 1.01-1.54). CONCLUSIONS: A greater HPCC program intensity reduces the risk of hospital death and hospital stay in the end-of-life. An early activation of this program can contribute to improve these EOL outcomes.
Asunto(s)
Cuidados Paliativos/métodos , Cuidado Terminal/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Hospitalización , Humanos , Italia , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Patients with histologically confirmed advanced colorectal cancer were randomized to receive folinic acid (FA; 500 mg/mq in 2-hour intravenous infusion) and 5-fluorouracil (5FU; 600 mg/mq given as an intravenous bolus 1 hour after FA), beginning every week for 6 weeks, followed by a 2-week rest period, either without hydroxyurea (HU, arm A) or with HU (35 mg/kg per day) given orally in three administrations (every 8 hours) starting 6 hours after 5FU administration (arm B). Six weekly doses were considered one course. One hundred eighty-two patients were randomized in this trial and 162 (89%) were evaluable for response: 81 patients in arm A and 81 patients in arm B. Objective response was observed in 18 (one complete response and 17 partial responses) of 81 evaluable patients (22%; 95% confidence interval, 13-31%) in arm A, and 24 (nine complete responses and 15 partial responses) of 81 patients (30%; 95% confidence interval, 20-40%) in arm B. There was no difference in terms of median time to progression and median survival. Gastrointestinal toxicity was the most frequently observed toxicity in both arms. The double modulation of 5FU, FA plus HU does not appear to be better than the classic 5FU plus FA schedule. This trial confirms that 5FU and FA reached a plateau of 20% to 30%.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/secundario , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Adulto , Anciano , Neoplasias Colorrectales/patología , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Hidroxiurea/administración & dosificación , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Análisis de SupervivenciaRESUMEN
PURPOSE: The nucleoside analog, gemcitabine, has shown activity as a single agent in the treatment of metastatic non-small-cell lung cancer (NSCLC). Its combination with cisplatin in preclinical models suggested synergy between the two drugs. The aim of the study was to evaluate the clinical efficacy and toxicity of the cisplatin-gemcitabine combination in advanced NSCLC. PATIENTS AND METHODS: Forty-eight consecutive previously untreated NSCLC patients entered the trial from January to June 1994. The median age was 60 years (range, 37 to 70) and performance status (PS) was 0 or 1; 22 patients had unresectable stage III disease (21 stage IIIB and one stage IIIA) and 26 had stage IV disease. Gemcitabine 1 g/m2 was administered weekly (days 1, 8, and 15) followed by a 1-week rest and cisplatin 100 mg/m2 on day 2 of each 28-day cycle. Survival and response were determined in accordance with the intention-to-treat principle in all enrolled patients. RESULTS: Of 48 assessable patients, one (stage IV) had a complete response (CR) and 25 achieved a partial response (PR). The overall response rate was 54% (95% confidence interval [CI], 40% to 68%). Thrombocytopenia was the main side effect, with 52% of patients experiencing grade III to IV toxicity, which was usually short-lived and responsible for the omission of gemcitabine administration on day 15 in 50% of chemotherapy courses. The median survival time was 61.5 weeks (95% CI, 40 to 71). CONCLUSION: The combination of gemcitabine and cisplatin induced a high response rate in both stage IIIB and IV NSCLC, with modest side effects. The regimen deserves further careful evaluation in a phase III prospective randomized trial.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/patología , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Esquema de Medicación , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neutropenia/inducido químicamente , Estudios Prospectivos , GemcitabinaRESUMEN
From June 1991 to August 1994, 61 patients with stage III unresectable non-small-cell lung cancer (NSCLC; 16 cases of stage IIIA with N2 bulky disease and 45 cases of stage IIIB) were treated with ifosfamide given i.v. at 3 g/m2 on day 1, carboplatin given i.v. at 200 mg/m2 on days 1 and 2, etoposide given i.v. at 120 mg/m2 on days 1-3 (ICE) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) given s.c. at 5 micrograms/kg on days 4-13. Chemotherapy was given every 3 weeks for up to three cycles and, unless the disease progressed, was followed by thoracic radiotherapy on the tumor volume (total dose 60 Gy) and mediastinum (40 Gy). All patients had measurable or evaluable unresectable disease and a performance status (Eastern Cooperative Oncology Group) of 0-1. Only 61% of the enrolled patients received the full program of chemoradiotherapy according to the study design. At the end of sequential chemo-radiotherapeutic treatment, 41% of the patients had an objective response (24 partial responses and 1 complete response), 31% showed no change and 28% had progressive disease. The response rate noted for patients in stage IIIA with N2 bulky disease and that recorded for patients in stage IIIB did not differ significantly. The median time to progression was 5.4 months and the median survival was 8.2 months, with the 1-year survival rate being 31%. Sites of progression were mostly intrathoracic. Haematological toxicity was the main side effect, with grade III-IV thrombocytopenia being reported in 24% of the 165 courses of intensive ICE chemotherapy given. Febrile neutropenia was described in six courses (three patients). Non-haematological toxicities and radiotherapy-related side effects were generally mild and easily manageable. In conclusion, in unresectable stage III NSCLC a short program of moderately intensified ICE chemotherapy with rhG-CSF protection followed by sequential radiotherapy failed to increase the percentage of objective responses and reached a median survival comparable with that previously achieved with standard doses.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Neoplasias Pulmonares/terapia , Radioterapia Adyuvante , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/secundario , Adenocarcinoma/terapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Progresión de la Enfermedad , Etopósido/administración & dosificación , Femenino , Enfermedades Hematológicas/inducido químicamente , Humanos , Ifosfamida/administración & dosificación , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Proteínas Recombinantes , Tasa de SupervivenciaRESUMEN
To evaluate the efficacy of a three-drug regimen vs. a two-drug CDDP based combination in the treatment of NSCLC, we conducted a three-arm randomized parallel trial comparing (a) CDDP (120 mg/m2 day 1) + etoposide (100 mg/m2 days 1-3) every 3 weeks (PE--arm A); (b) CDDP (120 mg/m2 every 4 weeks) + mitomycin (8 mg/m2 days 1, 29, 71) + vindesine (3 mg/m2 days 1, 8, 15, 22 every 2 weeks) (MVP--arm B); and (c) CDDP (120 mg/m2 day 1) + mitomycin (6 mg/m2 day 1) + ifosfamide (3 g/m2 day 2) every 3 weeks (MIC--arm C). From May 1989 to April 1992, 393 consecutive previously untreated patients with NSCLC Stage IIIB and IV entered the trial; 373 were evaluable for survival and 360 for response. The response rate was significantly better for both the three-drug regimens compared with PE (Table 3). Logistic regression model showed a significantly better response in patients with a good P.S. and in Stage IIIB. Main toxicity consisted of myelosuppression: neutropenia Grade III-IV was recorded in 14% (arm A), 15% (arm B) and 21% (arm C). Thrombocytopenia Grade III-IV was worst in arm C: 10% vs. 5% (arm A) and 3% (arm B). Nephrotoxicity Grade III-IV was more common in arm C: 3.5%. Toxic deaths were 11 (3%: three in arm A, five in arm B, three in arm C). From our data, the three-drug containing regimens, MVP and MIC, appear more active than the two-drug combination PE in treatment of advanced NSCLC.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Humanos , Ifosfamida/administración & dosificación , Ifosfamida/efectos adversos , Neoplasias Pulmonares/mortalidad , Masculino , Mitomicina/administración & dosificación , Mitomicina/efectos adversos , Tasa de Supervivencia , Resultado del Tratamiento , Vindesina/administración & dosificación , Vindesina/efectos adversosRESUMEN
BACKGROUND: Cisplatin-based chemotherapy is generally considered the most active treatment for advanced non-small-cell lung cancer. The combination of cisplatin and etoposide had for some time been the standard treatment at our center. Of the other active regimens, cisplatin in combination with mitomycin-C, vindesine or ifosfamide (MVP or MIC) showed the highest response rates. We decided to perform a comparative trial of the three 'best' regimens in order to define a possible standard regimen in advanced NSCLC. MATERIALS AND METHODS: From May 1989 to April 1992, 393 consecutive, previously untreated NSCLC patients, stages IIIB and IV, were randomized to receive either cisplatin (120 mg/sqm day 1) + etoposide (100 mg/sqm days 1-3) every 3 weeks (PE) or cisplatin (120 mg/sqm every 4 weeks) + mitomycin-C (8 mg/sqm days 1-29-71) + vindesine (3 mg/sqm days 1-8-15-22) (MVP) or cisplatin (120 mg/sqm day 1) + mitomycin-C (6 mg/sqm day 1) + ifosfamide (3 mg/sqm day 2) every 3 weeks (MIC). Of these, 382 were evaluable for survival and 360 for response. RESULTS: Response rates were statistically higher for both MIC (40%) and MVP (36%) than for the PE arm (23%). Survival estimates analyzed by the log-rank test showed a significant benefit (p < 0.04) for patients treated with three-drug regimens (MVP; MIC) as compared to those in the PE arm. The main toxicity was myelosuppression; thrombocytopenia WHO grade 3-4 was worse in the MIC arm; nephrotoxicity grade 3-4 was also more frequent in the MIC arm. CONCLUSIONS: A three-drug cisplatin-based regimen (MVP; MIC) should be considered as reference treatment in NSCLC.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Humanos , Ifosfamida/administración & dosificación , Ifosfamida/efectos adversos , Italia , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Mitomicina/administración & dosificación , Mitomicina/efectos adversos , Análisis Multivariante , Estadificación de Neoplasias , Estudios Retrospectivos , Tasa de Supervivencia , Vindesina/administración & dosificación , Vindesina/efectos adversosAsunto(s)
Síndrome de Inmunodeficiencia Adquirida/complicaciones , Brotes de Enfermedades , Sarcoma de Kaposi/epidemiología , Adulto , Linfocitos T CD4-Positivos , Femenino , Infecciones por VIH/epidemiología , Humanos , Italia/epidemiología , Recuento de Leucocitos , Persona de Mediana Edad , Sarcoma de Kaposi/mortalidadRESUMEN
Nodular bilateral pulmonary histoplasmosis: cyto-histological correlation. A case of nodular pulmonary histoplasmosis is reported. A 29 year old man was admitted to hospital with temperature and general weakness following a short stay in a tropical country. Laboratory investigation showed an increased E.S.R. and a routine chest-roentgenogram revealed multiple bilateral nodular lesions confirmed by CT scan. Smears obtained from fine-needle-aspiration biopsy showed the presence of epithelioid cell's clusters with a few giant-cells in a background of inflammatory elements and necrotic debris. The cytological picture was consistent with an inflammatory process with necrotizing granulomatous features. The clinical evolution and the radiological picture progression caused, nevertheless, suspicion of a metastatic tumor. The histological examination of a resected peripheral nodule confirmed the inflammatory nature of the process, revealing the presence of multiple roundish encapsulated conidia 2-4 microns in diameter scattered within a granulomatous and necrotic tissue. The fungi are clearly pinpointed by using special stains like Grocott method. Serological and microbiological investigations are necessary in order to confirm the diagnosis.
Asunto(s)
Histoplasmosis/patología , Enfermedades Pulmonares Fúngicas/patología , Adulto , Biopsia , Diagnóstico Diferencial , Granuloma/diagnóstico , Granuloma/patología , Histoplasma/aislamiento & purificación , Histoplasmosis/diagnóstico , Histoplasmosis/diagnóstico por imagen , Humanos , Inflamación , Pulmón/microbiología , Pulmón/patología , Enfermedades Pulmonares Fúngicas/diagnóstico , Enfermedades Pulmonares Fúngicas/diagnóstico por imagen , Masculino , Necrosis , Coloración y Etiquetado , Tomografía Computarizada por Rayos XRESUMEN
Treatment of gastric cancer still presents a challenge in cancer chemotherapy. In our Institute, from January 1981 to November 1984, 45 patients were given 5-fluorouracil (5FU) 600 mg/m2 Days 1, 8, 29, and 36; doxorubicin (A) 30 mg/m2 Days 1 and 29; mitomycin-C 10 mg/m2 Day 1 (FAM regimen) every 8 weeks. From December 1984 to October 1986, 26 patients were treated with 5FU 300 mg/m2 on Days 1-5, A 40 mg/m2 on Day 1, cisplatin (P) 100 mg/m2 on Day 1 (FAP regimen) every 3 weeks. In the FAM group, 42 patients are evaluable for response; 5 (12%) partial remission (PR), 9 stable disease (SD), and 28 progressions (PRO) were observed. Median duration of response (MDR) was 21 weeks (range 13-45) and the median survival (MS) in the whole group was 27 weeks. In the FAP group, 23 patients are evaluable: 2 CR (9%), 11 PR (47%), 2 SD (9%), and 8 PRO (34%) were observed; CR duration was 24 and 107+ weeks, respectively, MDR of PR was 22 weeks (5-35). The MS of all patients was 16 weeks. Toxicity (WHO criteria) was mild in the FAM group and severe in the FAP group. In spite of a higher objective response rate, the short MS and the severe toxicity observed in the FAP group do not merit recommendation of this regimen in patients with gastric cancer; therefore neither FAM nor FAP appear to be an ideal standard therapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Cisplatino/administración & dosificación , Cisplatino/toxicidad , Doxorrubicina/administración & dosificación , Evaluación de Medicamentos , Sinergismo Farmacológico , Femenino , Fluorouracilo/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Mitomicina/administración & dosificaciónAsunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Hidroxiurea/administración & dosificación , Leucovorina/administración & dosificación , Masculino , Persona de Mediana EdadRESUMEN
The pharmacokinetics of etoposide (VP 16) and teniposide (VM 26) were studied after intrapleural administration to 3 patients with lung cancer and malignant pleural effusion. Comparison with the kinetic behavior of intravenously infused VP 16 and VM 26 in the same patients suggests that intrapleural drug delivery achieves higher and longer-lasting pleural concentrations, thus providing a theoretical basis for the palliative treatment of malignant pleural effusions. Although no systemic toxicity was observed after intrapleural administration of either drug, 1 of the 3 patients developed a transient asymptomatic hemorrhagic pleurisy during the first 2 days after the drug, alerting to the possible local toxicity of such treatment.
Asunto(s)
Etopósido/farmacocinética , Neoplasias Pulmonares/tratamiento farmacológico , Derrame Pleural/tratamiento farmacológico , Podofilotoxina/análogos & derivados , Tenipósido/farmacocinética , Anciano , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Humanos , Infusiones Intravenosas , Neoplasias Pulmonares/metabolismo , Masculino , Persona de Mediana Edad , Derrame Pleural/metabolismo , Tenipósido/administración & dosificación , Tenipósido/efectos adversosAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Inflamación/inducido químicamente , Membrana Mucosa/efectos de los fármacos , Anciano , Cisplatino/administración & dosificación , Esquema de Medicación , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificaciónRESUMEN
A total of 52 consecutive, previously untreated patients with small-cell lung cancer (SCLC) were scheduled to receive six cycles of a combination of etoposide (75 mg/m2 per day) and cisplatin (20 mg/m2 per day), each cycle given over 5 consecutive days. In all, 28 patients had extensive disease (ED) and 24, limited disease (LD). After three cycles of chemotherapy, all responding patients were given chest radiotherapy (RT) (45 Gy in two split courses and 30 Gy in LD and ED, respectively); only patients with LD who achieved complete remission (CR) after three cycles of chemotherapy were given prophylactic brain irradiation (30 Gy). In the 51 evaluable patients, the overall response rate was 90%, with a 31% CR and a 59% partial remission (PR) rate. In LD and ED patients, 57% and 11% CR rates and 30% and 82% PR rates were noted, respectively. Myelosuppression was the most frequently observed toxicity. The median duration of response was 12 months in LD (range, 3-41 + months) and 7 months (range, 2-12 months) in ED; the median survival was 15 months in LD and 9.3 months in ED, respectively. In all 30% of LD patients are alive and well at a minimal follow-up of 18 months. This trial confirms the activity of the cisplatin-etoposide combination in SCLC.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Células Pequeñas/radioterapia , Cisplatino/administración & dosificación , Terapia Combinada , Etopósido/administración & dosificación , Femenino , Humanos , Neoplasias Pulmonares/radioterapia , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Twenty-seven evaluable patients with small cell lung cancer (SCLC) resistant to, or relapsed after induction combination chemotherapy (CT) were treated with etoposide (VP16) plus cisplatin (DDP). Previous treatment was: alternating CT with cyclophosphamide (C), adriamycin (A), methotrexate (M), procarbazine (P) (CAMP)/VP16, BCNU (B), hexamethylmelamine (H) (VP16 BH) in 16 patients; C, A, vincristine (CAV) in 6 patients; C, A, and VP16 (CAVP16) in 5 patients. We observed 2 (7%) complete responses (CR) and 9 (33%) partial responses (PR). Duration of CRs was 8 and 14 weeks, respectively. PRs lasted a median of 22 weeks (range 16-44). Seven of 21 (33%) patients previously treated with VP16 responded to DDP plus VP16 (D-V). These results confirm D-V regimen as active in SCLC patients even when heavily pretreated. Our 33% response in patients who had VP16 in their induction treatment regimen provides further evidence of an important potentiating effect of DDP, as reported in animal system.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Cisplatino/administración & dosificación , Ensayos Clínicos como Asunto , Etopósido/administración & dosificación , Estudios de Seguimiento , HumanosRESUMEN
The possible synergism of cisplatin (P) and 5-fluorouracil was studied in 38 consecutive patients with advanced or metastatic colorectal carcinoma. Cisplatin 60 mg/m2 i.v.q. 4 weeks and fluorouracil 600 mg/m2 i.v. weekly were administered for at least 2 cycles, on an out-patient basis, to 24 males and 14 females with a median age of 57 years and a median PS of 80 (Karnofsky). Evaluable lesions were: primary unresectable tumor in 2 patients, local recurrence in 11, liver, lung, bone and soft tissue metastases in 21, 7, 2 and 3 patients respectively. With a median number of 3 cycles administered to 35 evaluable patients, 6 partial responses, 16 unchanged and 13 progressions were observed. Responses were observed in the liver (2 patients), lungs (1) and soft tissues (3). Median remission duration was 15 weeks, median duration of 'unchanged' was 12 weeks. The overall median survival was 24 weeks (30.5 weeks for responders and 22.5 weeks for non-responders). Six patients were pretreated with chemotherapy not containing cisplatin (mainly adjuvant 5-FU). None of them responded. Toxicity was very tolerable with moderate nausea, vomiting and alopecia in the majority of the patients; bone marrow toxicity was generally mild with no blood transfusions required, no complications of myelosuppression (sepsis or bleeding) and no chemotherapy-related deaths. In this experience the combination of low dose cisplatin with fluorouracil, does not appear to significantly enhance 5-FU toxicity and the response rate is not superior to that reported with 5-FU alone. However, better designed schedule combinations with optimal doses, sequences and exposure time of the 2-drug regimen, seem necessary to obtain the biochemical events that support the potentiation.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Recto/tratamiento farmacológico , Adenocarcinoma/secundario , Adulto , Anciano , Cisplatino/administración & dosificación , Evaluación de Medicamentos , Femenino , Fluorouracilo/administración & dosificación , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Vinblastine 5-day continuous infusion in metastatic renal-cell carcinoma was evaluated in a Phase II trial. The dosage varied from 1.4 to 1.6 mg/m2/day every 3 weeks according to previous treatment and performance status (PS). From September 1983 to January 1986, 25 consecutive patients entered the study; 21 were evaluable for response and 23 were evaluable for toxicity. The median number of cycles administered was three (range, one to six). One complete response (liver) lasting 5 months, one partial response (lung) lasting 3 months, 12 cases of stable disease, and seven progressions were noted. Toxicity (WHO criteria) was relevant and mainly hematological: one treatment-related death occurred. Vinblastine continuous infusion did not demonstrate significant antineoplastic activity against metastatic renal-cell carcinoma.
Asunto(s)
Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Vinblastina/administración & dosificación , Adulto , Anciano , Evaluación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Vinblastina/efectos adversosRESUMEN
A combination of amikacin and ceftazidime was used as initial empiric therapy for the treatment of 25 evaluable febrile episodes (temperature greater than or equal to 38.5 degrees C) in leukopenic adult patients (wbc less than or equal to 1,000/mm3) with solid tumors, characterized by poor prognosis because of low performance status (median Karnofsky score: 50) and progressive disease (76% of cases). Nineteen (76%) of the 25 episodes responded to the initial empiric antibiotic combination. In the microbiologically documented infections, there was no significant difference in the response rate between bacteremia (67%) and localized infections (81%). The response in localized infections caused by gram-negative organisms (81%) was similar to that obtained in gram-positive organisms (82%), whereas gram-positive bacteremia responded better than gram-negative (100 vs 50%). No serious side effects were observed. Reversible nephrotoxicity occurred in 12% and hypokalemia in 20% of the patients treated. This antibiotic combination is a safe and efficacious empiric therapy for infections in leukopenic patients with solid neoplasia.
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Amicacina/administración & dosificación , Infecciones Bacterianas/tratamiento farmacológico , Ceftazidima/administración & dosificación , Fiebre/complicaciones , Leucopenia/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Amicacina/efectos adversos , Amicacina/uso terapéutico , Infecciones Bacterianas/complicaciones , Infecciones Bacterianas/microbiología , Ceftazidima/efectos adversos , Ceftazidima/uso terapéutico , Ensayos Clínicos como Asunto , Quimioterapia Combinada , Humanos , Tolerancia Inmunológica , Persona de Mediana Edad , Neoplasias/complicacionesRESUMEN
Three patients with lung cancer (1 SCLC, 2 NSCLC) and pericardial malignant effusion received 100 mg/m2 Teniposide (VM 26) i.v. and, 1 week later, 50 mg/m2 intrapericardially. Plasma, pericardial, and urine levels of the drug were measured in all patients after the two treatments by a HPLC assay. After intrapericardial administration, a high VM 26 concentration was found in the pericardial cavity and slow systemic drug absorption was observed. Since the drug AUC after intrapericardial administration was approximately 15-21 times that after i.v. administration, it could be that this treatment is more effective against neoplastic deposits localized in the pericardium. Even though this small series does not permit conclusions to be drawn on the efficacy of VM 26 given intrapericardially, the lack of local toxicity, minimal systemic toxicity, and the response observed in two out of three patients given intrapericardial VM 26 suggest that further investigation should be carried out on this method of VM 26 administration.
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Derrame Pericárdico/tratamiento farmacológico , Podofilotoxina/análogos & derivados , Tenipósido/farmacocinética , Anciano , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Células Pequeñas/complicaciones , Cromatografía Líquida de Alta Presión , Humanos , Infusiones Intravenosas , Infusiones Parenterales , Neoplasias Pulmonares/complicaciones , Masculino , Persona de Mediana Edad , Derrame Pericárdico/etiología , Derrame Pericárdico/metabolismo , Pericardio , Tenipósido/administración & dosificación , Tenipósido/sangreRESUMEN
The pharmacokinetics of 7-con-O-methylnogarol were investigated by HPLC assay with fluorometric detection in nine cancer patients with normal hepatic and renal function, after a 2-h infusion of 160 or 200 mg/m2. The drug disappeared from plasma biexponentially with a mean elimination half-life of 38 +/- 3 h; the mean apparent volume of distribution and the plasma clearance were 805 +/- 91 1/m2 and 14 +/- 2 1/h per m2. Within 48 h of administration, urinary excretion of the drug and its metabolite 7-con-O-methyl-N-demethylnogarol accounted for 2%-15% and 0.1%-6% of the dose, respectively. Neither 7-con-O-methylnogarol nor its N-demethyl derivative was conjugated with glucuronic acid or sulfate in detectable amounts.
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Daunorrubicina/análogos & derivados , Neoplasias/metabolismo , Nogalamicina/metabolismo , Anciano , Femenino , Semivida , Humanos , Infusiones Intravenosas , Cinética , Masculino , Menogaril , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Nogalamicina/análogos & derivados , Nogalamicina/sangre , Nogalamicina/uso terapéuticoRESUMEN
This prospective, randomized, nonblind study comparing the antiemetic effectiveness of high-dose IV metoclopramide and high-dose IV dexamethasone was performed in 78 advanced cancer patients. Chemotherapeutic treatment consisted in cisplatin at a high-dose (120 mg/m2) (HD-CDDP) and at a low-dose (LD-CDDP), either alone (60 mg/m2) or in combination with other chemotherapeutic agents (50 mg/m2). The evaluation of the effectiveness of antiemetic therapy was based on three parameters: prevention of vomiting ("major protection"), number of emetic episodes, and subjective preference. Out of 78 study patients, 67 were evaluable. Overall, metoclopramide proved to be statistically superior to dexamethasone in preventing vomiting (P less than 0.005), in reducing the median/mean number of emetic episodes (P less than 0.001/0.001), and in subjective preference (P less than 0.01). The results divided between HD-CDDP and LD-CDDP groups were also in favor of metoclopramide for reduction of the median/mean number of emetic episodes (P less than 0.001/0.001 for the HD-CDDP group and P less than 0.001/0.005 for the LD-CDDP group) and in subjective preference (P less than 0.001 and P less than 0.001 for the HD- and LD-CDDP groups, respectively). No statistical differences were noted when LD-CDDP was used in monochemotherapy, whereas when LD-CDDP was used in combination chemotherapy, statistical differences in favor of metoclopramide were noted again for the median/mean number of emetic episodes (P less than 0.01/0.05) and for subjective preference (P less than 0.01), even though the effectiveness of both antiemetic agents was greatly reduced. The evaluation of previously untreated patients reflected the overall results: for the HD-CDDP group all three parameters demonstrated statistical significance in favor of metoclopramide; for the LD-CDDP group, of all three parameters, prevention of vomiting (major protection) was the only one for which there was no significant difference. Mild sedation was the only side effect of metoclopramide. No extrapyramidal reactions were noted during this trial, but concomitant orphenadrine treatment was given. Dexamethasone was always well tolerated. In conclusion, high-dose IV metoclopramide demonstrated its superiority over high-dose IV dexamethasone in all subsets of our population except the LD-CDDP monochemotherapy group, in which the two antiemetics were found to be equivalent in effect.