Phase II study of perifosine and sorafenib dual-targeted therapy in patients with relapsed or refractory lymphoproliferative diseases

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Abstract

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.

Original languageEnglish
Pages (from-to)5641-5651
Number of pages11
JournalClinical Cancer Research
Volume20
Issue number22
DOIs
Publication statusPublished - Nov 15 2014

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Therapeutics
Hodgkin Disease
perifosine
sorafenib
Arthralgia
B-Cell Chronic Lymphocytic Leukemia
Drug-Related Side Effects and Adverse Reactions
Thrombocytopenia
Disease-Free Survival
Foot
Anemia
Diarrhea
Pneumonia
Research Design
Hand
Biomarkers
Lymphocytes
Cytokines
Safety
Skin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

@article{18d54800d67243458f74dfc5df55e597,
title = "Phase II study of perifosine and sorafenib dual-targeted therapy in patients with relapsed or refractory lymphoproliferative diseases",
abstract = "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.",
author = "Anna Guidetti and Carmelo Carlo-Stella and Locatelli, {Silvia L.} and Walter Malorni and Roberta Mortarini and Simonetta Viviani and Domenico Russo and Alfonso Marchian{\`o} and Roberto Sorasio and Anna Dodero and Lucia Farina and Laura Giordano and {Di Nicola}, Massimo and Andrea Anichini and Paolo Corradini and Gianni, {Alessandro M.}",
year = "2014",
month = "11",
day = "15",
doi = "10.1158/1078-0432.CCR-14-0770",
language = "English",
volume = "20",
pages = "5641--5651",
journal = "Clinical Cancer Research",
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TY - JOUR

T1 - Phase II study of perifosine and sorafenib dual-targeted therapy in patients with relapsed or refractory lymphoproliferative diseases

AU - Guidetti, Anna

AU - Carlo-Stella, Carmelo

AU - Locatelli, Silvia L.

AU - Malorni, Walter

AU - Mortarini, Roberta

AU - Viviani, Simonetta

AU - Russo, Domenico

AU - Marchianò, Alfonso

AU - Sorasio, Roberto

AU - Dodero, Anna

AU - Farina, Lucia

AU - Giordano, Laura

AU - Di Nicola, Massimo

AU - Anichini, Andrea

AU - Corradini, Paolo

AU - Gianni, Alessandro M.

PY - 2014/11/15

Y1 - 2014/11/15

N2 - 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.

AB - 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.

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U2 - 10.1158/1078-0432.CCR-14-0770

DO - 10.1158/1078-0432.CCR-14-0770

M3 - Article

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SP - 5641

EP - 5651

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

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ER -