RESUMEN
The purpose of this study was to determine the efficacy and safety of a new high-dose interleukin (IL)-2 regimen, given two days a week, for renal cell carcinoma. One hundred and four patients received IL-2 as a continuous i.v. infusion for 48 h at a daily dose of 24 x 10(6) IU/m2/day for 5 consecutive weeks. Patients were assessed for efficacy 4 and 8 weeks after the end of therapy, and patients who stabilized or responded received maintenance therapy with the same regimen. An objective clinical response was observed in 20 patients (complete in four, partial in 16). The dose of infused IL2 was significantly higher in the responders than in the nonresponders (p < 0.05). Clinical responses were significantly associated with a sedimentation rate of < 20 (p = 0.02), but no other prognostic factor was identified. Mean survival was 13 months. Grade 3 and 4 toxicities were rare, except for hypotension (58% of patients), the main dose-limiting toxic effect. Overall, 83% of the planned dose of IL-2 was given. IL-2 given 2 days a week is active in metastatic renal cell carcinoma and well tolerated.
Asunto(s)
Carcinoma de Células Renales/secundario , Carcinoma de Células Renales/terapia , Interleucina-2/administración & dosificación , Neoplasias Renales/secundario , Neoplasias Renales/terapia , Adulto , Carcinoma de Células Renales/inmunología , Femenino , Humanos , Interleucina-2/inmunología , Neoplasias Renales/inmunología , Masculino , Persona de Mediana Edad , Sobrevida , Factores de Tiempo , Pruebas de ToxicidadRESUMEN
BACKGROUND: The authors measured pharmacokinetic parameters before, during, and after immunotherapy by continuous intrapleural infusion of recombinant interleukin-2 (rIL-2) and correlated the resulting data with clinical effects in nine patients with malignant pleural effusion. METHODS: The underlying disease was malignant mesothelioma in five patients and adenocarcinoma in four patients. Continuous intrapleural infusion of rIL-2 was performed for 5 days at 21 x 10(6) IU/m2/day. Maximum tolerated dose previously was determined to be 24 x 10(6) IU/m2/day in a Phase I study. Peak levels, the areas under the concentration curve (AUC), and drug half-lives were measured in pleural fluid and plasma samples collected at 0 (baseline), 12, 24, 48, 72, 96, and 120 hours during infusion and at 2, 6, 8, 32, 44, 56, 80, and 120 hours after the end of infusion. RESULTS: High and prolonged intracavitary drug levels were achieved in all but two patients, with a statistically significant correlation between peak values and AUC. Four patients achieved objective responses according to World Health Organization criteria. Neither of the patients with undetectable rIL-2 levels had response to therapy. Serum rIL-2 levels were low regardless intrapleural levels. Mean AUC was lower in the plasma than in the pleural fluid. CONCLUSIONS: This study demonstrates that continuous intrapleural infusion of rIL-2 is an active method of treatment for malignant pleural effusion. The low serum levels associated with this method greatly improve tolerance. The results also indicate that the concentration and duration of intrapleural rIL-2 levels may depend on the extent of pleural invasion. Additional study is needed to confirm this finding.