RESUMO
BACKGROUND: The purpose of this study was to compare quality of life and overall toxicity in patients with advanced non-small-cell lung cancer (NSCLC) treated with vinorelbine-gemcitabine (VG) or carboplatin-paclitaxel (Taxol) (CP). PATIENTS AND METHODS: A total of 165 previously untreated patients were randomized to the two regimens. Quality of life was assessed by the Lung Cancer Symptom Scale (LCSS). Overall toxicity and secondary efficacy end points were evaluated by standard WHO criteria. RESULTS: There was no significant difference in overall quality of life between the two treatments. Neutropenia, thrombocytopenia, peripheral neuropathy, and alopecia, were more common in the CP arm, whereas constipation was more frequent in the VG arm. Response rates were 14.6% in the VG arm and 16.9% in the CP arm. Median survival times were 7.8 and 8.6 months, and 1 year survival rates were 38.4% and 31.9%, respectively. CONCLUSIONS: Patients treated with VG experienced lower toxicity, but overall quality of life was similar in both arms. Efficacy seemed comparable between VG and CP. Our study shows that VG is a viable alternative to platinum-based chemotherapy in patients with advanced NSCLC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Vimblastina/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Desoxicitidina/administração & dosagem , Feminino , Humanos , Infusões Intravenosas , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Qualidade de Vida , Análise de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagem , Vinorelbina , GencitabinaRESUMO
BACKGROUND: The authors conducted a Phase II study to evaluate the activity and toxicity of weekly docetaxel in second-line therapy for nonsmall cell lung carcinoma (NSCLC). METHODS: Patients with documented recurrent or refractory NSCLC, previously treated with no more than one chemotherapy regimen, were eligible if they had a performance status (PS) of 0-2, measurable or evaluable disease, and adequate organ function. Patients were treated with docetaxel 36 mg/m(2)/week for 6 consecutive weeks, administered intravenously with dexamethasone premedication. Cycles were repeated every 8 weeks. RESULTS: Thirty-one patients were enrolled. One patient was ineligible because of uncontrolled brain metastases. Hematologic toxicity was minimal. Nonhematologic toxicities were modest except for diarrhea and cumulative fatigue. There were no treatment-related deaths. The overall response rate was 10% (95% confidence interval [CI], 1.6-29%). The median survival time (MST) was 8.0 months. and the 1-year survival rate was 31% (95% CI, 17- 58%). Patients with PS 0-1 had a MST of 11.9 months with 1-year survival of 42%. CONCLUSIONS: Weekly docetaxel is very well tolerated as second-line therapy for NSCLC. The activity of this regimen appears to be comparable to the standard 3-week schedule. This regimen offers new opportunities for combination regimens, both as first- and second-line therapy for NSCLC.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Paclitaxel/análogos & derivados , Paclitaxel/uso terapêutico , Taxoides , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Fitogênicos/administração & dosagem , Docetaxel , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Análise de SobrevidaRESUMO
A 57-year-old woman presented with intermittent symptoms of intestinal obstruction. Workup provided nondiagnostic radiologic studies. An exploratory laparotomy revealed a segmental dilatation in the proximal ileum, which showed diffuse thickening of the intestinal wall. Microscopic examination of the affected area disclosed a diffuse transmural infiltrate composed of small lymphocytes, mature plasma cells, and lymphoplasmacytoid cells in different stages of maturation associated with extracellular periodic acid-Schiff-positive material. In addition, serum protein electrophoresis showed a monoclonal immunoglobulin M kappa paraprotein. Postoperative workup did not demonstrate evidence of systemic involvement. The morphologic features and immunohistochemical and molecular analyses were consistent with lymphoplasmacytoid lymphoma (immunocytoma). We report an unusual case of primary extranodal immunocytoma involving the small intestine and discuss its clinicopathologic features.
Assuntos
Neoplasias Intestinais/diagnóstico , Obstrução Intestinal/diagnóstico , Intestino Delgado , Leucemia Linfocítica Crônica de Células B/diagnóstico , Feminino , Humanos , Imunofenotipagem , Neoplasias Intestinais/classificação , Neoplasias Intestinais/patologia , Intestino Delgado/patologia , Leucemia Linfocítica Crônica de Células B/classificação , Leucemia Linfocítica Crônica de Células B/patologia , Pessoa de Meia-IdadeRESUMO
Several new chemotherapeutic agents were developed and tested in advanced non small-cell lung cancer (NSCLC) in the past decade. Vinorelbine and gemcitabine showed consistent single-agent activity in phase II and III trials and have been shown to be superior to older combinations when combined with cisplatin. However, toxicity associated with these regimens remains substantial, and nonplatinum alternatives are currently being explored. Based on the individual activity of vinorelbine and gemcitabine, their distinct mechanisms of action, and their mild, nonoverlapping toxicities, several trials evaluated their use in combination in patients with advanced NSCLC. Therapy has been administered in a convenient outpatient setting over a period of 1 hour. Different weekly schedules have been tested, but in general, toxicity is mild and the regimen is well tolerated, even in elderly patients or those with a poor performance status. Efficacy seems to be at least comparable to traditional platinum-based regimens, with respect to overall response rate and survival. In summary, vinorelbine/gemcitabine is an active and well-tolerated regimen and represents an option for the treatment of patients with advanced NSCLC. Randomized studies comparing this combination to reference platinum- or taxane-based regimens are needed to further evaluate the role of this combination in advanced NSCLC.
RESUMO
Several randomized trials have compared single-agent chemotherapy with combination chemotherapy in advanced non-small cell lung cancer. In general, response rates were higher with combination regimens, but their impact on survival is unclear. We conducted a meta-analysis of 25 trials involving a total of 5,156 patients with advanced non-small cell lung cancer randomized to a single-agent arm versus a combination arm. The results showed that combination chemotherapy produced a nearly twofold increase in response rate and a modestly improved 1-year survival rate compared with single-agent chemotherapy. However, toxicity was significantly increased, with a 3.6-fold increase in treatment-related mortality. In a subset analysis of trials using either a platinum analog or vinorelbine as single agents and as a component of the combination regimen, the difference was no longer statistically significant, suggesting that more active single agents provide similar survival with less toxicity than combination regimens. Based on these results, the Cancer and Leukemia Group B initiated a large randomized trial comparing paclitaxel with paclitaxel + carboplatin in stage IIIB-IV non-small cell lung cancer patients. The trial will be able to detect a 30% difference in survival. An extensive quality of life analysis and a resource utilization comparison will allow estimation of the incremental cost per quality of life-year gained. This trial will be the first in the United States to prospectively collect and analyze such data in a multidisciplinary approach.
Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
PURPOSE: Preclinical and clinical data suggest that topotecan may be more effective, and perhaps less toxic, when administered as a continuous intravenous infusion (CIVI). A previous Cancer and Leukemia Group B (CALGB) trial of topotecan, given on a daily bolus schedule in combination with cisplatin, produced more hematologic toxicity than expected with either drug alone. Therefore, we designed this phase I trial to define the dose-limiting toxicities (DLTs) and the recommended phase II doses of cisplatin in combination with topotecan administered as a CIVI. Population pharmacodynamic models for the combination also were investigated. PATIENTS AND METHODS: Patients with advanced solid tumors and a maximum of one prior chemotherapy regimen for metastatic disease were eligible if they had a performance status of 0 to 1 and adequate renal, hepatic, and bone marrow function. Prior treatment with camptothecins or platinum compounds and prior pelvic irradiation were not allowed. The initial schedule consisted of a fixed dose of topotecan 0.4 mg/m2/d administered as a CIVI for 21 days and escalating doses of cisplatin administered on days 1, 8, and 15 of a 28-day schedule, until the maximum tolerated dose (MTD) was achieved. After severe hematologic toxicity was observed in the first two patients, the topotecan infusion was shortened to 14 days, and the total dose of cisplatin was administered on day 1 in all subsequent patients. After the MTD was defined, that cohort was expanded to include a total of 12 assessable patients. Hematopoietic growth factors were not allowed. For the pharmacologic studies, total topotecan plasma concentrations were measured by high-pressure liquid chromatography (HPLC) during infusion on days 3, 8, and 11 on the first cycle, and the median steady-state concentration (Tss) was determined. Platinum plasma concentrations on day 3 were measured by atomic absorption spectrometry. RESULTS: Of the 32 patients enrolled, 28 were assessable for toxicity and 24 for response. The primary toxicity was hematologic, with both neutropenia and thrombocytopenia being dose-limiting. The MTD of cisplatin was 75 mg/m2 on day 1 in combination with topotecan 0.4 mg/m2/d for 14 days. At this dose level, three of a total of 12 assessable patients had DLT. The pharmacodynamic relationship between Tss and the absolute neutrophil count at the nadir (ANCn) was described by the following equation: log10 (ANCn)=4.23 - 0.47 x Tss - 0.01 x cisplatin dose (P < .0001; R2=0.64). The substitution of platinum concentration for cisplatin dose in this model did not result in a significant improvement. Three patients had a partial response: one with duodenal carcinoma; a second with small-cell lung cancer; and a third with melanoma. CONCLUSION: Cisplatin can be given safely in combination with CIVI topotecan. However, toxicity was still substantial. Based on the current results and our previous trial of this combination, we conclude that, when combined with cisplatin, CIVI topotecan does not seem to be advantageous compared with the more traditional daily bolus schedule.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Neutropenia/induzido quimicamente , Trombocitopenia/induzido quimicamente , Topotecan/administração & dosagem , Topotecan/efeitos adversosRESUMO
The authors define the dose-limiting toxicities and the recommended phase II doses of paclitaxel combined with etoposide, without and with filgrastim support. Patients with advanced solid tumors were eligible if they had a performance status of 0 to 2 and normal renal, hepatic, and bone marrow function. Patients with cardiac arrhythmias or congestive heart failure requiring medical therapy were excluded. Prior radiation was allowed only if it involved less than 30% of the marrow-containing skeleton. The dose of etoposide was fixed at 100 mg/m2/d for 3 days beginning on day 1. Paclitaxel was administered over 3 hours on day 4. The dose of paclitaxel was escalated until the maximum tolerated dose (MTD), without and with filgrastim 5 microg/kg (or 300 microg total dose) subcutaneously beginning on day 5, was reached. Treatment cycles were repeated every 21 days. Of 39 patients entered, 37 were evaluable for toxicity and 30 for response. The principal toxicity was neutropenia. Without filgrastim, the MTD of paclitaxel was 150 mg/m2. With filgrastim, the dose of paclitaxel was escalated to 250 mg/m2 in combination with etoposide 100 mg/m2. One episode of pulmonary toxicity was observed. Five patients responded: two with previously treated non-small-cell lung cancer (NSCLC), two with refractory small-cell lung cancer (SCLC), and one with refractory germ-cell tumor (GCT). We conclude that paclitaxel and etoposide can be given in combination at clinically relevant doses with filgrastim support. In this phase I trial, a dose of paclitaxel of 200 mg/m2 on day 4 and etoposide at 100 mg/m2/d on days 1-3, with filgrastim 5 microg/kg beginning on day 5, was found to be well tolerated, and can be recommended for future studies. Without filgrastim, a paclitaxel dose of 150 mg/m2 with the same dose of etoposide can also be recommended.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/tratamento farmacológico , Germinoma/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Esquema de Medicação , Etoposídeo/administração & dosagem , Feminino , Filgrastim , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Proteínas RecombinantesRESUMO
BACKGROUND: This meta-analysis was conducted to compare the effects of single agent versus combination chemotherapy on response rate, toxicity, and survival of patients with advanced nonsmall cell lung carcinoma (NSCLC). METHODS: The authors reviewed randomized clinical trials published in the medical literature and the reference lists of relevant articles. Objective response rate, survival at 6 and 12 months, and the incidence of treatment-related death were compared among all patients receiving single agent chemotherapy and those receiving combination chemotherapy. A subgroup analysis for all outcomes was conducted for 10 trials published between 1989 and 1996 that used a platinum analogue or vinorelbine as the single agent arm. RESULTS: The authors identified 38 potentially eligible trials, 25 of which (with a total of 5156 patients) were included in the meta-analysis. Overall, combination chemotherapy produced a nearly 2-fold increase in response rate compared with single agent chemotherapy (response rate [RR], 1.93; 95% confidence interval [CI], 1.54-2.42). However, combination chemotherapy also increased toxicity significantly, including a 3.6-fold increase in the risk of treatment-related death (RR, 3.5; 95% CI, 1.8-6.7). Survival at 6 months (RR, 1.10; 95% CI, 1.02-1.19) and 12 months (RR, 1.22; 95% CI, 1.03-1.45) was modestly superior with combination chemotherapy when all trials are included. However, when a platinum analogue or vinorelbine are used as single agents, this difference was no longer statistically significant at 6 months (RR, 1.03; 95% CI, 0.92-1.15) or at 12 months (RR, 1.10; 95% CI, 0.94-1.43). CONCLUSIONS: Combination chemotherapy increased objective response and toxicity rates compared with single-agent chemotherapy. Survival was prolonged only modestly with combination chemotherapy but not significantly so when more active single agents were used.
Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Antineoplásicos/efeitos adversos , Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Causas de Morte , Cisplatino/análogos & derivados , Cisplatino/uso terapêutico , Intervalos de Confiança , Seguimentos , Humanos , Incidência , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento , Vimblastina/análogos & derivados , Vimblastina/uso terapêutico , VinorelbinaRESUMO
Chemotherapy has produced only modest survival benefits in patients with advanced non-small cell lung cancer. Several new chemotherapeutic agents developed in the past few years have shown promising activity in non-small cell lung cancer. It is likely that these agents, used alone or in combination, will further improve the outcome for patients with advanced non-small cell lung cancer. Chemotherapy has made a much stronger impact in small cell lung cancer, but the majority of patients still die from disease. The new chemotherapeutic agents may also contribute to improved survival of patients with small cell lung cancer, especially when used in combination with thoracic radiotherapy in those who present with limited disease.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/radioterapia , Terapia Combinada , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Estadiamento de Neoplasias , Taxa de Sobrevida , Resultado do TratamentoAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neutropenia/induzido quimicamente , Sepse/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Carcinoma de Células Pequenas/tratamento farmacológico , Cisplatino/efeitos adversos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/efeitos adversos , Sepse/imunologia , TopotecanRESUMO
PURPOSE: To define the dose-limiting toxicities (DLTs) and the recommended phase II doses of paclitaxel combined with topotecan, without and with filgrastim support. PATIENTS AND METHODS: Patients with advanced solid tumors and a maximum of one prior chemotherapy regimen for metastatic disease were eligible if they had a performance status of 0 to 1 and normal renal, hepatic, and bone marrow function. Prior treatment with taxanes or comptothecin analogs, and prior pelvic irradiation were not allowed. Patients with a history of cardiac disease or on medications known to affect cardiac conduction were excluded. The dose of topotecan was fixed at 1.0 mg/m2/d for 5 days. The dose of paclitaxel was escalated until the maximum-tolerated dose (MTD), without and with filgrastim 5 micrograms/kg subcutaneously (SC) on days 6 to 14, was reached. Paclitaxel was administered over 3 hours on day 1 before topotecan. Treatment cycles were repeated every 21 days. RESULTS: Of 46 patients entered, 45 were assessable for toxicity and 34 for response. The principal toxicity was neutropenia. Without filgrastim, the MTD of paclitaxel was 80 mg/m2 on day 1 in combination with topotecan 1.0 mg/m2/d for 5 days. With filgrastim, the dose of paclitaxel was escalated to 230 mg/m2 in combination with the same dose of topotecan. At this dose level, one patient had hematologic DLT and a second patient developed neuromuscular DLT. Three patients had a partial response (PR): one with head and neck cancer, a second with non-small-cell lung cancer, and the third with colon cancer. CONCLUSION: We conclude that paclitaxel can be given at clinically relevant doses in combination with topotecan and filgrastim. The recommended dose for phase II studies is paclitaxel 230 mg/m2 on day 1 and topotecan 1.0 mg/m2/day for 5 days with filgrastim 5 micrograms/kg on days 6 to 14.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Feminino , Filgrastim , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Neutropenia/terapia , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Indução de Remissão , Trombocitopenia/induzido quimicamente , Topotecan , Estados UnidosRESUMO
Etoposide and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) each exhibit substantial activity against a variety of solid tumors. Etoposide promotes accumulation of cells in late S phase and in G2. Paclitaxel causes cell arrest in G2 and M. In this phase I trial, an empiric combination of a fixed dose of etoposide daily for 3 days followed by a 3-hour intravenous infusion of escalating doses of paclitaxel on day 4 is being tested. Cycles are repeated every 3 weeks. Dose level I, etoposide 100 mg/m2 intravenously days 1 to 3 and paclitaxel 80 mg/m2 intravenously day 4, was well tolerated. Dose level 2, with paclitaxel at 120 mg/m2, is near completion and appears tolerable as well. Further escalation of the paclitaxel dose is anticipated. Once the maximum tolerated dose of this combination is defined, growth factor will be added and further escalation of the paclitaxel dose will be attempted.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Esquema de Medicação , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Metástase Neoplásica , Neutropenia/induzido quimicamente , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Trombocitopenia/induzido quimicamenteAssuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/classificação , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimioterapia Adjuvante , Terapia Combinada , Humanos , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/terapia , Radioterapia AdjuvanteRESUMO
A patient with a history of partial gastrectomy presented with severe anemia, neutropenia, intestinal malabsorption, and was found to be severely copper-deficient. The anemia and neutropenia corrected promptly with the administration of intravenous cupric chloride. This case suggests that partial gastrectomy with or without intestinal malabsorption can result in copper deficiency and should be considered in differential diagnosis of severe anemia and neutropenia.
Assuntos
Anemia/etiologia , Cobre/deficiência , Síndromes de Malabsorção/complicações , Neutropenia/etiologia , Adulto , Feminino , Gastrectomia/efeitos adversos , HumanosRESUMO
PURPOSE: The objectives of this phase I trial were to determine the dose-limiting toxicities (DLTs) of the novel topoisomerase I inhibitor topotecan combined with cisplatin, to define the maximum-tolerated doses (MTDs) of the combination without and with the use of filgrastim, and to define recommended doses for phase II trials. PATIENTS AND METHODS: Patients with advanced solid tumors were eligible if they had normal bone marrow, renal, and hepatic function and had not previously been treated with platinum compounds. Topotecan was administered intravenously on days 1 through 5 and cisplatin was administered intravenously on day 1 of a 21-day cycle. The topotecan dose was fixed at 1.0 mg/m2/d on the first four dose levels, and cisplatin was escalated in 25-mg/m2 increments from 25 to 100 mg/m2 without filgrastim. After encountering DLT, the dose of cisplatin was decreased by one level and topotecan dose escalation was attempted. After defining the MTD without growth factor, the study proceeded with escalating cisplatin doses to define the MTD with filgrastim 5 micrograms/kg subcutaneously (SC) daily starting on day 6 of treatment. Priming with filgrastim 5 micrograms/kg SC on days -6 to -2 before the first course was explored last. RESULTS: Of 38 patients entered, 37 were eligible, 35 assessable for toxicity in the first course, and 28 assessable for response. The principal toxicity was grade 4 neutropenia, which had to last more than 7 days to be considered dose-limiting. No DLT was observed at the starting cisplatin dose of 25 mg/m2 (dose level 1). On level 2 (cisplatin 50 mg/m2, one patient had dose-limiting neutropenia and one patient had grade 3 renal toxicity. On level 3 (cisplatin 75 mg/m2), two patients had dose-limiting neutropenia. Therefore, cisplatin dose escalation was stopped. On dose level 5 (cisplatin 50 mg/m2 and topotecan 1.25 mg/m2/d), one patient had grade 4 neutropenia that lasted more than 7 days and one patient died of neutropenic sepsis. The remaining dose levels used topotecan 1.0 mg/m2/d plus cisplatin 75 mg/m2 (level 6) and 100 mg/m2 (levels 7 and 8) with filgrastim. No DLT was observed on level 6. On level 7, two patients had dose-limiting neutropenia and one patient had grade 3 hyperbilirubinemia. Priming with filgrastim on level 8 demonstrated no obvious advantage over level 7, and one patient had grade 4 thrombocytopenia that lasted more than 7 days. Three patients with non-small-cell lung cancer achieved a partial response and one patient with breast cancer had a complete response. CONCLUSION: Topotecan and cisplatin in combination cause more neutropenia than expected from either drug given alone at the same dosage. The recommended phase II doses are topotecan 1.0 mg/m2/d for 5 days in combination with cisplatin 50 mg/m2 on day 1 without filgrastim or cisplatin 75 mg/m2 on day 1 with filgrastim support.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Cisplatino/administração & dosagem , Neoplasias/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Camptotecina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Relação Dose-Resposta a Droga , Feminino , Filgrastim , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/tratamento farmacológico , Neutropenia/induzido quimicamente , Proteínas Recombinantes/administração & dosagem , Neoplasias das Glândulas Salivares/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , TopotecanRESUMO
The optimal treatment strategy for patients with locally advanced (stage III) non-small-cell lung cancer remains controversial. Primary surgical resection or conventional thoracic irradiation alone results in poor long-term survival for the majority of stage III patients. Several multimodality strategies are reviewed in this article. Radiation followed by surgery may increase resectability, but its effects on survival are unproven. Sequential chemotherapy and radiation have demonstrated a survival advantage for selected stage III patients. Chemotherapy followed by surgery has also shown encouraging results, and additional studies are in progress. Concurrent chemoradiotherapy has shown conflicting results in a few randomized studies. Concurrent chemotherapy and radiation followed by surgery has been tested only in phase II trials and awaits further studies.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Terapia Combinada , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Taxa de SobrevidaRESUMO
PIP: Kaposi's sarcoma (KS) is a complex neoplasm of cells of endothelial and fibroblast origin, whose proliferation is maintained by the viral product Tat, cytokines, and maybe environmental factors. It was among the first noted clinical manifestations of AIDS and remains the most common malignancy observed in patients infected with HIV, yet an optimal treatment strategy remains to be identified. The authors discuss current options and future directions for the systemic treatment of KS. They do not, however, address local forms of treatment. It is concluded that angiogenesis inhibitors may provide a novel therapeutic approach in the near future, while single agent cytotoxic chemotherapy and combination chemotherapy may induce remissions in the majority of patients along with relief from the morbidity of edema, disfigurement, and pain. Interferon is effective mainly in patients who are not severely immunocompromised. Finally, systemic therapy for AIDS-associated KS must be integrated with antiretroviral therapy, prophylaxis for opportunistic infections, and appropriate hematological support. Sections explore the etiology and pathogenesis of KS, rationale for systemic treatment, single-agent chemotherapy, combination chemotherapy, chemotherapy and antiretroviral agents, interferon, interferon and antiretroviral therapy, interferon and chemotherapy, other biological agents, angiostatic compounds, and anti-Tat therapy. Innovative treatment approaches to KS may ultimately prove applicable to many other neoplastic disorders.^ieng
Assuntos
Antineoplásicos/uso terapêutico , Sarcoma de Kaposi/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antivirais/uso terapêutico , Produtos do Gene tat/antagonistas & inibidores , Fatores de Crescimento de Células Hematopoéticas/uso terapêutico , Humanos , Fatores Imunológicos/uso terapêutico , Interferons/uso terapêutico , Interleucina-2/uso terapêutico , Produtos do Gene tat do Vírus da Imunodeficiência HumanaRESUMO
PURPOSE: This study attempted to identify novel chemotherapeutic agents with greater than 15% activity in non-small-cell lung cancer (NSCLC). DESIGN: An English language literature search, which included abstracts and original articles, and a review of bibliographies of identified articles, were used. RESULTS: Nine new agents, analogs, or old agents used in new doses or schedules were identified: CPT-11, topotecan, taxol, taxotere, Navelbine (Burroughs Wellcome, Research Triangle Park, NC), chronic oral etoposide, edatrexate, gemcitabine, and high-dose epirubicin. Results of phase I and II trials that involved these agents alone or as part of combination regimens are presented. CONCLUSION: Several new chemotherapeutic agents with activity against NSCLC are now available. Response rates compare favorably with those of available standard drugs. These new drugs are being integrated into multiagent combinations. Large-scale phase III trials that compare these new combinations with current standard approaches will be necessary to determine whether or not these new drugs will have a positive impact on survival in patients with NSCLC.