Phase II study of perifosine and sorafenib dual-targeted therapy in patients with relapsed or refractory lymphoproliferative diseases
Autor: | Paolo Corradini, Laura Giordano, Alessandro M. Gianni, Massimo Di Nicola, Lucia Farina, Simonetta Viviani, Alfonso Marchianò, Roberto Sorasio, Anna Guidetti, Walter Malorni, Carmelo Carlo-Stella, Domenico Russo, Andrea Anichini, Roberta Mortarini, Silvia L. Locatelli, Anna Dodero |
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Rok vydání: | 2014 |
Předmět: |
Oncology
Sorafenib Adult Male Niacinamide medicine.medical_specialty Cancer Research Combination therapy Adolescent Chronic lymphocytic leukemia Phosphorylcholine Phases of clinical research chemistry.chemical_compound Young Adult Recurrence Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Medicine (all) Molecular Targeted Therapy Extracellular Signal-Regulated MAP Kinases Pneumonitis Aged Neoplasm Staging business.industry Phenylurea Compounds Cancer Middle Aged medicine.disease Perifosine Lymphoproliferative Disorders Surgery Treatment Outcome chemistry Female business Proto-Oncogene Proteins c-akt Progressive disease Biomarkers medicine.drug |
Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 20(22) |
ISSN: | 1557-3265 |
Popis: | Purpose: To evaluate safety and activity of perifosine and sorafenib combination therapy in patients with lymphoproliferative diseases. Experimental Design: Patients with relapsed and refractory lymphoproliferative diseases received perifosine (50 mg twice daily) for 1 month. Patients achieving less than partial response (PR) after perifosine alone were administered the combination therapy [perifosine plus sorafenib (400 mg twice daily)] until progressive disease (PD) or unacceptable toxicity occurred. The pERK and pAKT in peripheral blood lymphocytes as well as serum cytokine levels were investigated as predictive biomarkers of response. Results: Forty patients enrolled in this study. After 1 month of perifosine alone, 36 who achieved less than PR went on to combination therapy, whereas four patients with chronic lymphocytic leukemia (CLL) who achieved PR continued with perifosine alone for a median of 10 months (range, 4–21). The most common drug-related toxicities were grade 1–2 anemia (17%), thrombocytopenia (9%), diarrhea (25%), joint pain (22%), and hand–foot skin reaction (25%). Three patients experienced grade 3 pneumonitis. Eight patients (22%) achieved PR, 15 (42%) achieved stable disease, and 13 (36%) experienced PD. A 28% PR rate was recorded for 25 patients with Hodgkin lymphoma. Among all patients, median overall survival and progression-free survival were 16 and 5 months, respectively. Early reductions in pERK and pAKT significantly correlated with the probability of clinical response. Conclusions: Perifosine and sorafenib combination therapy is feasible with manageable toxicity and demonstrates promising activity in patients with Hodgkin lymphoma. The predictive value of pERK and pAKT should be confirmed in a larger patient cohort. Clin Cancer Res; 20(22); 5641–51. ©2014 AACR. |
Databáze: | OpenAIRE |
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