RESUMEN
Renal-cell carcinoma (RCC) is susceptible to immune therapy including the use of the nonmyeloablative allogeneic transplantation (NST). However, NST can produce severe toxicity, might not be appropriate for many patients with metastatic RCC. Other novel allogeneic immunotherapies are designed to induce an autologous immune response directed against the malignancy. In single-arm phase II trials, thalidomide has demonstrated a modest activity in the treatment of advanced RCC. Here we present a case report in which a patient with advanced RCC in the absence of transplant conditioning, that was receiving thalidomide, was infused with partially HLA-matched irradiated allogeneic lymphocytes. In this patient a complete response with weak acute graft-versus-host disease (GVHD) was observed. No evidence of the disease was present over the subsequent 36 months survival of the patient, suggesting that the infusions may have played a major role in the antineoplastic effect. A potential mechanism of this protocol may involve a host-versus-graft reactions-mediated antitumor effect against the malignancy. In addition, the present results suggest that a combination protocol with alternate treatment (e.g., chemotherapy) schedules merit further investigation in the management of various malignancies.
Asunto(s)
Carcinoma de Células Renales/terapia , Antígenos HLA/análisis , Prueba de Histocompatibilidad/métodos , Neoplasias Renales/terapia , Transfusión de Linfocitos , Talidomida/administración & dosificación , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/inmunología , Terapia Combinada , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/terapia , Antígenos HLA/efectos de la radiación , Humanos , Neoplasias Renales/diagnóstico , Neoplasias Renales/inmunología , Transfusión de Linfocitos/métodos , Masculino , Persona de Mediana Edad , Trasplante HomólogoRESUMEN
The objective of this study was to evaluate the efficacy and safety of the POF regimen (biweekly 5-fluorouracil/leucovorin combined with paclitaxel and oxaliplatin) as first-line treatment for advanced gastric cancer (AGC). Twenty-seven previously untreated patients with advanced adenocarcinoma of the gastric or gastroesophageal junction were eligible for this study. The chemotherapy regimen consisted of a 3-hour infusion of paclitaxel (135 mg/m(2)) followed by oxaliplatin (85 mg/m(2)) and leucovorin (400 mg/m(2)), administered simultaneously over a 2-hour infusion period, followed by an infusion of 5-fluorouracil (2400 mg/m(2)) over a 46-hour period. Twenty-one patients had measurable lesions: four complete responses, eight partial responses and seven stable diseases. At a median follow-up of 610 days, median survival was 348 days. Frequent grade 3 to 4 toxicities were: neutropenia (29.6%), stomatitis (7.4%), nausea (7.4%), vomiting (7.4%), hepatic dysfunction (3.7%), and fatigue (18.5%). No treatment-related deaths occurred. The POF regimen appears to be efficacious and is well tolerated in patients with AGC.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Estimación de Kaplan-Meier , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Oxaliplatino , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Resultado del TratamientoRESUMEN
BACKGROUND & OBJECTIVE: Standard chemotherapy for advanced gastric cancer remains undefined. Phase II trials show that taxol is effective in treating advanced gastric cancer. This multi-center prospective open randomized controlled study was to compare the efficacy of Taxol plus calcium folinate (CF)/5-fluorouracil (5-FU), Taxol plus oxaliplatin (OXA), and CF/5-FU plus cisplatin (DDP) on advanced gastric cancer, and analyze their toxicities. METHODS: Patients with measurable unresectable and/or metastatic gastric carcinoma were randomized into CF/5-FU+DDP (control), CF/5-FU + Taxol, and Taxol + OXA groups, and received up to 8 cycles of chemotherapy. Treatment efficacy and adverse events were evaluated according to WHO criteria. RESULTS: A total of 180 patients were enrolled from May 2002 to May 2004, and randomized into the 3 groups; each group contained 60 patients. Of the 180 patients, 14 received 2 cycles of chemotherapy, 49 received 4 cycles, and 103 received 8 cycles. Treatment outcomes of 166 cases were evaluable. The response rate (RR) of naive patients or the patients with retroperitoneal lymph node metastasis was significantly higher in CF/5-FU+Taxol and Taxol+OXA groups than in control group (50.00% and 80.00% vs. 20.75%, P<0.05; 65.96% and 85.71% vs. 36.36%, P<0.05). But the RR of the patients with liver metastasis was similar among the 3 groups (28.57% and 39.13% vs. 34.62%, P>0.05). The occurrence rates of nausea/vomiting, anepithymia, stomatitis, and kidney damage were lower in study groups than in control group, but the occurrence rates of myelosuppression and peripheral nerve damage were higher in study groups than in control group. Allergic response occurred in 7 (5.88%) patients in study group, and 3 (2.52%) of them were serious. There was no treatment-related death. CONCLUSIONS: Despite its hematotoxicity, the treatment efficacy of Taxol-based combination regimens on advanced gastric cancer is better than that of CF/5-FU + DDP regimen with tolerable toxicities. We recommend Taxol-based combination regimens as first-line regimens for advanced gastric cancer.