Related Experiment Video

Updated: May 22, 2026

Percutaneous Hepatic Perfusion (PHP) with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver
09:02

Percutaneous Hepatic Perfusion (PHP) with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver

Published on: July 31, 2016

Perifosine plus lenalidomide and dexamethasone in relapsed and relapsed/refractory multiple myeloma: a Phase I

Andrzej J Jakubowiak1, Paul G Richardson, Todd Zimmerman

  • 1University of Michigan Cancer Center, Ann Arbor, MI, USA. ajakubowiak@medicine.bsd.uchicago.edu

British Journal of Haematology
|May 30, 2012
PubMed

Insights

The combination of perifosine, lenalidomide, and dexamethasone shows promising activity and good tolerability in patients with relapsed or refractory multiple myeloma (MM). This novel regimen warrants further investigation for MM treatment.

Area of Science:

  • Hematology
  • Clinical Oncology
  • Pharmacology

Background:

  • Lenalidomide-dexamethasone is an established active regimen for multiple myeloma (MM).
  • Preclinical studies indicated that perifosine, an Akt inhibitor, enhances MM cell sensitivity to lenalidomide and dexamethasone.

Purpose of the Study:

  • To assess the safety and determine the maximum-tolerated dose (MTD) of perifosine in combination with lenalidomide and dexamethasone.
  • To evaluate the clinical activity of this combination in patients with relapsed and relapsed/refractory multiple myeloma.

Main Methods:

  • Phase I, multicenter, single-arm study.
  • Escalating doses of perifosine (50-100 mg daily) combined with lenalidomide (15-25 mg daily, days 1-21) and dexamethasone (20-40 mg weekly).
  • Thirty-two patients with relapsed/refractory MM were enrolled across four dose cohorts.

Main Results:

  • The MTD was not reached; the combination was generally well tolerated.
  • Common adverse events included fatigue and diarrhea (grade 1-2), and neutropenia, hypophosphatemia, thrombocytopenia, and leucopenia (grade 3-4).
  • Of 30 evaluable patients, 73% achieved a minimal response or better, with 50% achieving a partial response or better. Median progression-free survival was 10.8 months and median overall survival was 30.6 months.

Conclusions:

  • Perifosine-lenalidomide-dexamethasone is a well-tolerated regimen.
  • The combination demonstrated encouraging clinical activity in relapsed and relapsed/refractory multiple myeloma.
  • Response correlated with phospho-Akt levels in pharmacodynamic studies.

More Related Videos

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

Related Concept Videos

Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Bioavailability Study Design: Single Versus Multiple Dose Studies01:11

Bioavailability Study Design: Single Versus Multiple Dose Studies

Bioavailability studies are essential for understanding how a drug is absorbed, distributed, metabolized, and excreted in the body. These studies assess the extent and rate at which the active pharmaceutical agent becomes available at the site of action. The design of bioavailability studies can involve single-dose or multiple-dose regimens, each with distinct advantages and limitations.Single-dose studies are the preferred approach due to their simplicity and reduced drug exposure for...
Drug Accumulation During Multiple Dosing: Intermittent IV Infusions01:24

Drug Accumulation During Multiple Dosing: Intermittent IV Infusions

Intermittent intravenous (IV) infusion is a method of drug administration where medications are delivered over short infusion periods followed by intervals of no drug delivery. This approach helps to prevent sustained high drug concentrations in the bloodstream, reducing the risk of adverse effects associated with prolonged exposure. Unlike continuous infusion, steady-state concentrations may not be achieved during a single dosing cycle but can be reached through repeated...
Chemotherapy-Induced Nausea and Vomiting: Dopamine Receptor Antagonists01:29

Chemotherapy-Induced Nausea and Vomiting: Dopamine Receptor Antagonists

Dopamine receptor antagonists, also known as antipsychotic agents, are critical in managing chemotherapy-induced vomiting. These antiemetic agents block dopamine receptors in the chemoreceptor trigger zone (CTZ), inhibiting signal transmission to the vomiting center. Antipsychotic agents encompass phenothiazines (PTZ), butyrophenones, benzamides, and thienobenzodiazepines (Zyprexa), which are utilized for their antiemetic and sedative properties.
Phenothiazines, such as prochlorperazine...