According to results recently published in the journal Cancer, the use of the chemotherapy agent Doxil® (pegylated liposomal doxorubicin) in place of Adriamycin® (doxorubicin) in the chemotherapy regimen referred to as VAD reduces the risk of serious side effects to the heart while maintaining effectiveness in the treatment of multiple myeloma.
Multiple myeloma is a cancer involving important immune cells called plasma cells. Plasma cells aid the body in fighting infection by producing specialized proteins called antibodies that are able to target and/or kill foreign cells.
In multiple myeloma, cancerous plasma cells produce abnormal and excessive antibodies that cannot properly fight infection. In addition, the cancerous plasma cells accumulate in the bone marrow, suppressing the normal formation and function of other cells that are necessary for normal production of blood cells and immune functions. The excessive accumulation of cancer cells in the bone marrow ultimately leads to the formation of tumors in the bone and to the breakdown of bone.
One of the most commonly used regimens for treatment of patients with multiple myeloma is VAD (Oncovin® [vincristine], doxorubicin, and dexamethasone). However, cumulative exposure to doxorubicin can lead to irreversible cardiac (heart) dysfunction, such as congestive heart failure (CHF). CHF is caused by direct damage to the heart by the chemotherapy drug doxorubicin and may result in heart failure for some patients. The side effects caused by doxorubicin during treatment can also result in treatment delays and dose reductions; in these cases, the cancer receives less treatment.
Researchers have developed a revised version of doxorubicin, called Doxil, which has a slow release mechanism. With this mechanism, small doses of the active drug are constantly delivered in the body, and the active form of Doxil stays available in the body for a longer period of time. In addition, increased concentrations of the drug accumulate in cancer cells as opposed to healthy cells, reducing side effects directly attributed to the agent.
The slow release formulation also requires fewer drug administrations, relieving patients of extra hospital visits and time spent receiving treatment. Doxil is currently approved for the treatment of recurrent ovarian cancer and AIDS-related Kaposi’s sarcoma. It is in clinical trials for other types of cancer. Doxil has recently demonstrated a lower incidence of cardiac side effects than doxorubicin while providing similar anticancer activity.
A multicenter phase III trial (phase of trial prior to FDA review) was recently conducted by institutions within the U.S. to further evaluate Doxil as a substitute for doxorubicin in the VAD regimen among patients with multiple myeloma. This trial included 192 patients with newly diagnosed multiple myeloma who were treated with either conventional VAD or with a regimen called DVd, which substitutes Doxil for doxorubicin. The DVd regimen proved to be a promising substitution for VAD:
- Anticancer responses were achieved in 44.4% of patients treated with DVd, and 39% of patients treated with VAD.
- A complete disappearance of cancer was achieved in 3.1% of patients treated with DVd, compared with no patients treated with VAD.
- Progression-free survival was similar between the two treatment groups at one, two, and three years.
- Less supportive care was required for patients treated with DVd compared to those treated with VAD.
- Side effects to the heart were reduced with the use of DVd compared to VAD.
The researchers concluded that DVd appears to be a valid substitution for VAD as initial treatment for multiple myeloma; serious side effects to the heart were reduced while effectiveness was maintained. Patients diagnosed with multiple myeloma who are to undergo treatment with VAD may wish to speak with their physician regarding their individual risks and benefits of treatment with DVd .
Reference: Rifkin RM, Gregory SA, Mohrbacher A, et al. Pegylated liposomal doxorubicin, vincristine, and dexamethasone provide significant reduction in toxicity compared with doxorubicin, vincristine, and dexamethasone in patients with newly diagnosed multiple myeloma. Cancer. 2006;106: 848 – 858.