RESUMEN
A cisplatin-resistant cell line, SBC-3/CDDP, was established from a human small-cell lung cancer cell line, SBC-3. The SBC-3/CDDP cells were 13.1-fold more resistant to cisplatin than the parent SBC-3 cells. We investigated the cellular changes of this cell line with regard to the development of resistance to cisplatin. The SBC-3/CDDP cells showed various characteristics as follows: a) increased intracellular glutathione and glutathione S-transferase content b) decreased intracellular accumulation of cisplatin, c) increased topoisomerase I activity and the same topoisomerase II activity as the parent SBC-3 cells, and 4) strong cross-resistance to the platinum analogues and mitomycin C, moderate cross-resistance to 7-ethyl-10-hydroxy-camptothecin (SN-38), 4-hydroperoxy cyclophosphamide, etoposide, Adriamycin and methotrexate, and collateral sensitivity to vinca alkaloids and 5-fluorouracil. From these observations, the SBC-3/CDDP cells could be useful as a well characterized cisplatin-resistant cell line, and the resistance pattem in this cell line will give us much information for eradication of cisplatin-resistant tumor cells.
Asunto(s)
Antineoplásicos/farmacología , Carcinoma de Células Pequeñas/tratamiento farmacológico , Cisplatino/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Vincristina/farmacología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/análisis , Carcinoma de Células Pequeñas/patología , ADN-Topoisomerasas de Tipo I/metabolismo , ADN-Topoisomerasas de Tipo II/metabolismo , Resistencia a Antineoplásicos , Glutatión/análisis , Humanos , Neoplasias Pulmonares/patología , Células Tumorales Cultivadas , Vincristina/farmacocinéticaAsunto(s)
Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Taxoides , Hidrocarburos Aromáticos con Puentes/uso terapéutico , Camptotecina/uso terapéutico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Humanos , Compuestos Organoplatinos/uso terapéutico , Alcaloides de la Vinca/uso terapéutico , GemcitabinaRESUMEN
BACKGROUND: Hepatitis B after the withdrawal of cytotoxic chemotherapy in hepatitis B virus (HBV) carriers is well known and may lead to fatal hepatic failure. We retrospectively analyzed the prevalence of HBV carriers, the incidence, and the risk factors of hepatitis B in the treatment of malignant lymphoma. PATIENTS AND METHODS: HBV carriers were defined as patients with positive HBs-antigen, either with normal or abnormal serum aminotransferase level at patient presentation. Questionnaires to the members of the Japan Lymphoma Treatment Study Group included general information, details about HBV carriers, and further information about hepatitis B. RESULTS: Among 1380 patients collected from eight institutions, 45 patients (3.26%) were determined to be HBV carriers, Hepatitis B developed in 17 of the HBV carrying patients (37.8%). Seven of those 17 (41.2%) died of hepatic failure. Hepatitis developed at a high rate in patients who were negative for HBe-antigen (50%), and who had received second- or third-generation chemotherapy (63.2%). CONCLUSION: We confirmed that hepatitis B developed with high frequency in HBV carriers with malignant lymphoma. Moreover, hepatitis often resulted in fatal hepatic failure. It is necessary to prevent the hepatitis B developing in HBV carriers when receiving intensive chemotherapy for malignant lymphoma.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Portador Sano/epidemiología , Virus de la Hepatitis B , Hepatitis B/epidemiología , Linfoma/tratamiento farmacológico , Linfoma/virología , Adolescente , Adulto , Anciano , Femenino , Humanos , Incidencia , Japón/epidemiología , Linfoma/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Here we review the current treatments for small-cell lung cancer. Cisplatin and etoposide, combined with concurrent or alternating thoracic irradiation, have been considered to be the standard therapy for patients with limited disease. Dose-intensive weekly chemotherapy and high-dose chemotherapy with autologous stem cell transplantation have failed to increase survival in patients with extensive disease. Promising new drugs such as irinotecan and taxol may improve survival in patients with extensive disease.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Ensayos Clínicos como Asunto , Terapia Combinada , Humanos , Irinotecán , Paclitaxel/administración & dosificaciónRESUMEN
201T1 single photon emission computed tomography (201T1 SPECT) was used to evaluate 18 patients with large opacities due to silicosis and 22 others with bronchogenic carcinoma. An early scan and a delayed scan were obtained and the retention index was calculated from the early ratio and the delayed ratio. In patients with silicosis, the retention index and the two ratios were significantly lower than in the patients with bronchogenic carcinoma (p < 0.01). In patients with stable shadows on chest X-ray films due to large opacities of silicosis, the delayed ratio was the same as or lower than the early ratio. However, in patients with silicosis who had high activity in large opacities, the delayed ratio was higher than the early ratio. These results suggest that 201)T1 SPECT is useful for evaluating the activity of large opacities in patients with silicosis and for differentiating large opacities caused by silicosis from those caused by bronchogenic carcinoma.
Asunto(s)
Carcinoma Broncogénico/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Silicosis/diagnóstico por imagen , Radioisótopos de Talio , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiografía Torácica , Talio , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
The acute respiratory distress syndrome developed twice within 4 months in a patient with liver cirrhosis and diabetes mellitus. The diagnosis was made from the diffuse alveolar shadows seen on a chest X-ray film and a lung injury score of 3.3. The initial episode resolved quickly with steroid pulse therapy. The second episode resolved to some extent after the same therapy, but the patient died of hepatic and renal failure followed by acute pneumonia. The causes of the first and second episodes were considered to be different and the outcome depended on liver and kidney function. We report this case because the acute respiratory distress syndrome rarely occurs within 4 months.
Asunto(s)
Complicaciones de la Diabetes , Cirrosis Hepática/complicaciones , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Enfermedad Aguda , Antiinflamatorios/administración & dosificación , Resultado Fatal , Humanos , Infusiones Intravenosas , Masculino , Metilprednisolona/administración & dosificación , Persona de Mediana Edad , Recurrencia , Síndrome de Dificultad Respiratoria/etiologíaRESUMEN
A 63-year-old woman complaining of a non-productive cough was referred to our hospital. A chest X-ray film and computed tomographic scan showed a large mass in the S9 region of the right lung, and many intrapulmonary nodules with thin-walled cavities. A transbronchial biopsy specimen revealed moderately differentiated adenocarcinoma of bronchial gland origin. By the end of four cycles of chemotherapy with vindesine, ifosfamide, and cisplatin, the primary mass had markedly regressed, the many metastases had disappeared, and a few bullous lesions remained. On the second admission, many intrapulmonary metastases and cavities were seen again. Although some of the cavities may have been associated with regrowth of residual cancer cells around the remaining bullae, some nodules showed newly-developed thin-walled cavities, and in others bullous lesions developed again. These observations indicate that a check valve mechanism may operate in the formation of the thin-walled cavities.
Asunto(s)
Adenocarcinoma/patología , Neoplasias Pulmonares/patología , Neoplasias Primarias Múltiples/patología , Adenocarcinoma/secundario , Neoplasias Óseas/secundario , Neoplasias Encefálicas/secundario , Femenino , Humanos , Persona de Mediana EdadRESUMEN
Ten patients with stage I-II SCLC received IC-AS between 1984 and 1993. As induction chemotherapy, COMP-VAN alternating chemotherapy and CAV-PVP hybrid chemotherapy were administered. The former consisted of a 4-drug combination of cyclophosphamide (CPA), vincristine (VCR), methotrexate (MTX) and procarbazine alternated with a 3-drug combination of etoposide (ETP), adriamycin (ADM) and nimustine every 4 weeks. In the latter, a 3-drug combination of CPA, ADM and VCR given on day 1, and a 2-drug combination of ETP and cisplatin on day 8, were repeated every 4 weeks. All the patients had an objective response, including one complete response by induction chemotherapy. Post-operative pathology revealed SCLC in 4 patients, adenocarcinoma in 2 and no tumor (pathological CR) in 4. Four patients relapsed, and a intrathoracic relapse was experienced in only 2 patients. Six patients have died: 3 from relapsing SCLC, 2 from stomach cancer, and 1 from squamous lung cancer, who was salvaged from relapsing SCLC. The median survival time was 27.5 months, and the 3-year survival rate 37.5%. These results indicate that IC-AS is highly effective for stage I-II SCLC and warrant additional studies comparing IC-AS with chemo-radiotherapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Pequeñas/terapia , Neoplasias Pulmonares/terapia , Anciano , Carcinoma de Células Pequeñas/mortalidad , Terapia Combinada , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Esquema de Medicación , Etopósido/administración & dosificación , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Nimustina/administración & dosificación , Terapia Recuperativa , Vincristina/administración & dosificaciónRESUMEN
A 68-year-old man was referred to our hospital for further examination of a gingival mass. Chest radiographs and magnetic resonance imaging disclosed a bulky mass originating in the upper portion of the left lung, in contact with a chronic empyema lesion that first occurred after resection for pulmonary tuberculosis. Examination of a specimen obtained by percutaneous needle biopsy of the mass led to the diagnosis of large-cell carcinoma. Laboratory findings on admission showed marked leukocytosis (48,100/microliter) without evidence of severe a bacterial infection. The level of G-CSF in serum was abnormally high (246 pg/ml, normal value: < 30 pg/ml). Chemotherapy with vindesine, ifosfamide, and cisplatin resulted in shrinkage of the gingival mass, and a decrease in the G-CSF level to 66 pg/ml. Immunohistochemical staining with an anti-G-CSF monoclonal antibody to the primary lung tumor and the gingival mass obtained at autopsy was positive for cytoplasmic G-CSF.
Asunto(s)
Carcinoma de Células Grandes/metabolismo , Carcinoma de Células Grandes/secundario , Neoplasias Gingivales/metabolismo , Neoplasias Gingivales/secundario , Factor Estimulante de Colonias de Granulocitos/biosíntesis , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Anciano , Humanos , MasculinoRESUMEN
We investigated the changes in cellular components and neutrophil chemotactic factors in pleural fluid from 19 lung cancer patients who received intrapleural injection of OK-432 to treat malignant pleurisy. Not only neutrophil chemotactic activity (NCA) but also neutrophil count and percentage were increased significantly at 6 hours after OK-432 injection. The neutrophil count was significantly correlated with NCA level. The levels of C5a and IL-8 in pleural fluid were increased significantly after OK-432 injection. The increased IL-8 level was associated with a increase of both NCA and neutrophil count. OK-432 treatment also induced a marked increase of IL-1 beta and IL-6 in pleural fluid. Thus, intrapleural injection of OK-432 induced production of neutrophil chemotactic factors (IL-8 and C5a) and cytokines (IL-1 beta and IL-6), which eventually attracted neutrophils into the pleural space. These observations suggest that neutrophil migration mediated by these factors and cytokines may contribute to the sclerosing effects of OK-432 treatment.
Asunto(s)
Factores Quimiotácticos/biosíntesis , Neutrófilos/efectos de los fármacos , Picibanil/uso terapéutico , Derrame Pleural Maligno/tratamiento farmacológico , Adulto , Anciano , Complemento C5a/biosíntesis , Femenino , Humanos , Interleucina-1/biosíntesis , Interleucina-6/biosíntesis , Interleucina-8/biosíntesis , Recuento de Leucocitos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Neutrófilos/metabolismo , Derrame Pleural Maligno/metabolismo , Derrame Pleural Maligno/patologíaRESUMEN
This paper overviews the recent treatment results for small cell lung cancer. The last decade has brought only a small improvement, supposedly, mainly due to the development of drug resistance. However, current trials of non-cross-resistant chemotherapy, dose-intensive weekly chemotherapy, late intensification with autologous bone marrow transplantation, and combined modality treatment with thoracic irradiation have shown a substantial advance in the treatment of small cell lung cancer.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/terapia , Trasplante de Médula Ósea , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Cisplatino/administración & dosificación , Ensayos Clínicos como Asunto , Terapia Combinada , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Esquema de Medicación , Etopósido/administración & dosificación , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Vincristina/administración & dosificaciónRESUMEN
A new human lymphoma cell line derived from pulmonary non-Hodgkin's lymphoma that developed in a renal transplant recipient was established from the patient's pleural effusion and designated PTLC-1. PTLC-1 grew aggressively in suspension, forming very loose clumps with a doubling time of about 18.9 h. The morphological, chromosomal, and immunophenotypic characteristics of the patient's tumor cells and PTLC-1 cells were very similar. PTLC-1 showed a monoclonal rearrangement of IgH gene and was highly tumorigenic in athymic nude mice. In situ hybridization, Southern blot hybridization and polymerase chain reaction demonstrated the presence of Epstein-Barr virus (EBV) genome in the patient's tumor and PTLC-1. PTLC-1 has been maintained in culture for over 60 months. Since EBV has been implicated in the pathogenesis of post-transplant lymphoma, this new cell line should serve as a useful experimental model for studying the etiology and biology of lymphoma developing in organ transplant recipients.
Asunto(s)
Herpesvirus Humano 4/aislamiento & purificación , Trasplante de Riñón/efectos adversos , Linfoma no Hodgkin/patología , Células Tumorales Cultivadas , Adulto , Animales , Secuencia de Bases , Aberraciones Cromosómicas , ADN de Neoplasias/análisis , Humanos , Linfoma no Hodgkin/etiología , Linfoma no Hodgkin/genética , Masculino , Ratones , Datos de Secuencia Molecular , Trasplante de Neoplasias , Trasplante HeterólogoRESUMEN
A 59-year-old man was admitted in July, 1985 because of generalized lymphadenopathy and hypercalcemia. The biopsy specimen of the left inguinal lymph node showed diffuse large cell lymphoma. He achieved a complete remission (CR) in July, 1986 by CHOP therapy. In January, 1992, he visited the outpatient clinic with splenomegaly, and swelling of the left axillary and left supraclavicular lymph nodes. The biopsy specimen of the axillary lymph node showed follicular small cleaved cell lymphoma. Because the spleen and the lymph nodes regressed after the biopsy, he has been followed up without any specific treatment for lymphoma. Histologic change from low-grade lymphoma into more aggressive histologic pattern is well documented. However the converse phenomenon, occurrence of low-grade lymphoma after intermediate-, or high-grade lymphoma has rarely been reported. Histological examination is mandatory when a patient with diffuse large cell lymphoma is suspected to have relapsing disease after the long-term CR.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma Folicular/patología , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Humanos , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Recurrencia , Vincristina/administración & dosificaciónAsunto(s)
Antineoplásicos/administración & dosificación , Neoplasias Pulmonares/terapia , Dosificación Radioterapéutica , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Carcinoma de Células Pequeñas/tratamiento farmacológico , Carcinoma de Células Pequeñas/radioterapia , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapiaRESUMEN
Two patients with unresectable gastric cancer accompanied with multiple liver metastases were treated with a 3-drug combination consisting of etoposide, adriamycin, and cisplatin (EAP) as neoadjuvant chemotherapy. After confirmation of maximal response to EAP, both patients received surgical resection of the primary tumor and infusion of cisplatin and 5-FU into hepatic artery, and they survived 15.0 and 15.8 months, respectively. These results indicate that neoadjuvant chemotherapy with EAP regimen is useful in the treatment of advanced gastric cancer.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/secundario , Adenocarcinoma/cirugía , Anciano , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Doxorrubicina/administración & dosificación , Esquema de Medicación , Etopósido/administración & dosificación , Arteria Hepática , Humanos , Bombas de Infusión Implantables , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugíaRESUMEN
In order to assess the effectiveness of sequential TI for the treatment of LD SCLC, we analyzed 69 patients who had received CAV-PVP chemotherapy consisting of cyclophosphamide, adriamycin, vincristine, cisplatin and etoposide, plus sequential TI between 1986 and 1992. TI was delivered at a total dose of 50 Gy, 5 fractions/week for 5 weeks, once patients achieved a maximal response to chemotherapy. Responding patients also received PCI at a total dose of 30 Gy, 5 fractions/week for 3 weeks. Thirty patients achieved CR by chemotherapy and an additional 10 achieved CR after TI, resulting in a CR rate of 58.0%. Of 40 patients achieving CR, 24 have relapsed so far; the primary (in 15) and the brain (in 4) were the major sites of relapse despite TI and PCI. The median survival time was 18.4 months, with a 2-year survival rate of 39% and 3-year survival rate of 20%. Almost all the patients encountered grade 3 or grade 4 leukopenia while receiving chemotherapy, but the toxicity of TI was generally mild. This treatment is useful for patients with LD SCLC.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Pequeñas/terapia , Cisplatino/administración & dosificación , Etopósido/administración & dosificación , Neoplasias Pulmonares/terapia , Adulto , Anciano , Terapia Combinada , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dosificación Radioterapéutica , Vincristina/uso terapéuticoRESUMEN
Cholera toxin (CT) inhibited the growth of three out of 10 small cell lung cancer (SCLC) cell lines and two out of seven non-small cell lung cancer (NSCLC) cell lines when tested by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. These CT-sensitive as well as CT-resistant cell lines bound well to the non-toxic CT-B subunit-fluorescein isothiocyanate conjugate (FITC-CTB) when assayed by flow cytometry. Using the reaction of horseradish peroxidase-conjugated CT-B (HRP-CTB) on thin-layer chromatography (TLC), we analyzed gangliosides extracted from SCLC cell lines, CT-resistant SBC-1, minimally CT-sensitive SBC-3 and CT-sensitive SBC-5. HRP-CTB was found to react not only with GM1, but also with Fuc-GM1, GD1b and other gangliosides on TLC. Although CT-resistant SBC-1 cells bound well to FITC-CTB, the binding of gangliosides extracted from SBC-1 cells to HRP-CTB was markedly decreased when compared to those from CT-sensitive SBC-5 cells. The CT resistance of the minimally CT-sensitive SBC-3 cell lines, which binds weakly FITC-CTB and HRP-CTB, was partially reversed by exogenous GM1 pretreatment. These observations suggest that the amount of gangliosides, such as GM1, Fuc-GM1 and GD1b, on the cells, rather than the CT-binding ability to the cells, plays a major role in cytotoxicity by CT.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Células Pequeñas/tratamiento farmacológico , Toxina del Cólera/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Pequeñas/metabolismo , Carcinoma de Células Pequeñas/patología , División Celular/efectos de los fármacos , Toxina del Cólera/metabolismo , Cromatografía en Capa Delgada , Citometría de Flujo , Gangliósidos/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Células Tumorales CultivadasRESUMEN
BACKGROUND: Small cell lung cancer (SCLC) is highly sensitive to chemotherapy. Despite the introduction of intensive combination chemotherapy, long-term disease-free survivors are still rare. The emergence of drug-resistant tumor cells during chemotherapy is presumed to be the major cause of poor outcome. METHODS: A pilot Phase II study of hybrid chemotherapy for patients with SCLC was conducted between October 1986 and March 1988. Dose and schedule for each drug in the regimen were as follows: cyclophosphamide, 700 mg/m2 intravenously (IV), day 1; doxorubicin, 30 mg/m2 IV, day 1; vincristine, 1.4 mg/m2 IV, day 1; cisplatin, 60 mg/m2 IV, day 8; and etoposide, 100 mg/m2 IV, days 8 and 9. Courses were repeated every 4 weeks for up to six cycles. Patients with limited disease (LD) received chest irradiation of 5000 cGy when a maximal response was achieved. Only patients with LD who achieved a complete response (CR) received prophylactic cranial irradiation of 3000 cGy. RESULTS: Thirty-six patients were enrolled and fully evaluated for tumor response and toxicity. All 20 patients with LD responded to the regimen, and 14 (70%) of those achieved a CR. Of 16 patients with extensive disease (ED), 7 CR and 7 partial responses were noted, indicating an overall response rate of 88%. The median survival time was 23.6 months for patients with LD and 12.6 months for those with ED. Myelosuppression was the major toxicity, but it was generally well tolerated. CONCLUSIONS: These results indicate that the hybrid regimen is a highly active one for the treatment of patients with SCLC and warrants additional clinical trials.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Pequeñas/tratamiento farmacológico , Cisplatino/administración & dosificación , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Vincristina/administración & dosificación , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Células Pequeñas/patología , Carcinoma de Células Pequeñas/radioterapia , Carcinoma de Células Pequeñas/secundario , Cisplatino/efectos adversos , Terapia Combinada , Irradiación Craneana , Ciclofosfamida/efectos adversos , Doxorrubicina/efectos adversos , Etopósido/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/radioterapia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Proyectos Piloto , Inducción de Remisión , Tasa de Supervivencia , Vincristina/efectos adversosRESUMEN
Diffuse large-cell lymphoma (DLCL) is a neoplasm that is curable with chemotherapy in an appreciable percentage of patients. However, not all patients are cured and the best drug combination and optimal dose intensity have not yet been established. In an attempt to improve complete response rate and survival with minimal toxicity, we devised an alternating combination chemotherapy consisting of CHOP-Bleo (cyclophosphamide, doxorubicin, vincristine, prednisolone, and bleomycin) and POEM-Bleo (prednisolone, vincristine, etoposide, mitoxantrone, and bleomycin). Between March 1986 and October 1990, 30 newly-diagnosed patients with advanced DLCL were treated with the regimen. Of these 30 patients, 14 (47%) were 61 years of age or more, 15 (50%) had stage IV disease, 14 (47%) presented with constitutional symptoms, and 7 (23%) had T-cell lymphoma. After the completion of therapy, 23 (77%) achieved a complete response and 6 (20%) had a partial response. The actuarial relapse-free survival at 5 years is 52% and the overall survival projected to 5 years is 47%. Toxicity was generally mild and well tolerated. Although this alternating regimen had substantial activity as front-line chemotherapy for advanced DLCL, we conclude that the observed response rate and survival do not essentially differ from those achieved with conventional regimens and further clinical trials are thus not warranted.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Adulto , Anciano , Bleomicina/administración & dosificación , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Prednisolona/administración & dosificación , Prednisona/administración & dosificación , Inducción de Remisión , Vincristina/administración & dosificaciónRESUMEN
Antitumor activities of five platinum analogs, including cisplatin, carboplatin, 254-S, DWA2114R, and NK121, were compared using five human lung cancer cell lines and 19 tumor specimens obtained from lung cancer patients. The antitumor activity was evaluated by determining the ratio of the maximum tolerated dose of each drug to the 70% tumor growth inhibitory concentration in a colony assay. Cisplatin was the most potent agent, followed by 254-S and carboplatin. DWA2114R and NK121 were less potent than cisplatin and 254-S. Cross-resistance to adriamycin was also investigated using an adriamycin-resistant small cell lung cancer subline, SBC -3/ADM30. SBC-3/ADM30 was 1.7- to 4.0-fold more resistant to cisplatin, carboplatin, NK121, and DWA2114R, than was the parent line, SBC-3, and the subline was 2.0-fold more sensitive to 254-S. Using SBC-3, in vitro combination effects of etoposide and cisplatin, carboplatin, or 254-S were evaluated by the median-effect principle. Synergism was noted when cisplatin and etoposide were combined at a fixed molar ratio of 1:1. Combination of carboplatin and etoposide showed an additive effect. The combination of 254-S and etoposide was antagonistic at low concentrations, but was markedly synergistic at higher concentrations. These data suggested the efficacy of 254-S in the treatment of lung cancer.