RESUMEN
PURPOSE: Bendamustine and rituximab (BR) has been established as a superior frontline therapy over R-CHOP in the treatment of follicular lymphoma (FL). Yttrium-90 Ibritumomab tiuxetan (90YIT) is an effective consolidation strategy after chemotherapy induction. This prospective, single-arm, multicenter, phase II trial evaluated the response rate, progression-free survival (PFS), and tolerability of BR followed by consolidation with 90YIT in patients with untreated FL. PATIENTS AND METHODS: The study included grade 1 to 3a FL patients aged ≥18 years, chemotherapy-naïve, and requiring treatment for stage II-IV disease. Study treatment included an initial rituximab treatment, followed by four cycles of BR. Patients were eligible for consolidation with 90YIT, 6 to 12 weeks after BR, if they obtained at least a partial response after induction had adequate count recovery and bone marrow infiltration < 25%. RESULTS: Thirty-nine patients were treated. Eighty-two percent had an intermediate or high-risk Follicular Lymphoma International Prognostic Index score, and 6 of 39 (15%) were grade 3a. The response rate was 94.8%, and the complete response(CR)/CR unconfirmed (CRu) rate was 77% in the intention-to-treat analysis. The conversion rate from PR to CR/Cru after 90YIT was 81%. After median follow-up of 45 months, the PFS was 0.71 (95% confidence interval, 0.57-0.89). CONCLUSIONS: This report demonstrates that four cycles of BR followed by consolidation with 90YIT achieve high response rates that are durable. In addition, consolidation with 90YIT results in a high conversion rate of PR to CR/CRu. A short course of BR followed by 90YIT is a safe and effective regimen for frontline treatment of FL.
Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Clorhidrato de Bendamustina/administración & dosificación , Linfoma Folicular/tratamiento farmacológico , Rituximab/administración & dosificación , Adulto , Anciano , Anticuerpos Monoclonales/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Clorhidrato de Bendamustina/efectos adversos , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Esquema de Medicación , Femenino , Humanos , Linfoma Folicular/mortalidad , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Estudios Prospectivos , Radioinmunoterapia/efectos adversos , Radioinmunoterapia/métodos , Inducción de Remisión/métodos , Rituximab/efectos adversosRESUMEN
We report a phase 1 study of pharmacokinetics, dosimetry, toxicity, and response of (131)I anti-tenascin chimeric 81C6 for the treatment of lymphoma. Nine patients received a dosimetric dose of 370 MBq (10 mCi). Three patients received an administered activity of 1480 MBq (40 mCi), and 2 developed hematologic toxicity that required stem cell infusion. Six patients received an administered activity of 1110 MBq (30 mCi), and 2 developed toxicity that required stem cell infusion. The clearance of whole-body activity was monoexponential with a mean effective half-life of 110 hours (range, 90-136 hours) and a mean effective whole-body residence time of 159 hours (range, 130-196 hours). There was rapid uptake within the viscera; however, tumor uptake was slower. Activity in normal viscera decreased proportional to the whole body; however, tumor sites presented a slow clearance (T(1/2), 86-191 hours). The mean absorbed dose to whole-body was 67 cGy (range, 51-89 hours), whereas the dose to tumor sites was 963 cGy (range, 363-1517 cGy). Despite lack of a "blocking" antibody, 1 of 9 patients attained a complete remission and 1 a partial remission. These data demonstrate this radiopharmaceutical to be an encouraging agent for the treatment of lymphoma particularly if methods to protect the normal viscera are developed.
Asunto(s)
Anticuerpos Monoclonales/toxicidad , Radioisótopos de Yodo/toxicidad , Linfoma no Hodgkin/radioterapia , Animales , Anticuerpos Monoclonales/farmacocinética , Transporte Biológico , Biopsia , Médula Ósea/patología , Femenino , Humanos , Inmunotoxinas/farmacocinética , Inmunotoxinas/toxicidad , Radioisótopos de Yodo/farmacocinética , Ganglios Linfáticos/patología , Linfoma no Hodgkin/patología , Masculino , Ratones , Selección de Paciente , Tenascina/análisis , Distribución Tisular , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Many patients with recurrent, intermediate or high-grade non-Hodgkin lymphoma (NHL) may not respond to or are not candidates for aggressive salvage chemotherapy. Effective, less toxic regimens are needed. Although high-dose taxanes have not been reported to be very effective for the treatment of lymphoma, different delivery rates may allow for different mechanisms of action to be manifest and result in a different toxicity profile and response rate. The current study tested this hypothesis by using low-dose, weekly paclitaxel in patients with recurrent or refractory NHL. METHODS: Adults age > 18 years with refractory or recurrent, aggressive NHL who were not considered curable with standard high-dose therapy received paclitaxel at a dose of 80 mg/m2 weekly for 5 weeks for 2 cycles. RESULTS: Thirty-four patients with refractory NHL and 4 patients with recurrent disease were treated. Approximately 45% of the patients had achieved a prior disease remission. The median number of prior regimens received was 3, 74% of the patients had an International Prognostic Index of > or = 3 at the time of study entry, and 29% had failed high-dose therapy with autologous hematopoietic support. Only one patient encountered severe toxicity (sepsis). Myelosuppression was reported to occur in approximately 20% of patients. A total of 10 patients (26%) achieved a complete disease response and 4 patients (11%) achieved a partial response. CONCLUSIONS: In the current study, low-dose, weekly paclitaxel therapy was found to provide a well tolerated and less toxic approach to the treatment of refractory NHL, with encouraging responses noted in heavily pretreated patients. However, evaluation in patients with an earlier stage of disease is warranted.