Micrograph showing a lymph node invaded by ductal breast carcinoma, with extension of the tumour beyond the lymph node. Credit: Nephron/Wikipedia
Palbociclib, a new oral drug whose efficacy in combating breast cancer has been demonstrated alone and in combination with endocrine therapy, also has potential to combat other types of cancer, according to a literature review and original research at Abramson Cancer Center (ACC) in the University of Pennsylvania.
Palbociclib targets the rapid division of tumor cells by inhibiting the activity of the enzymes CDK4 and CDK6, which propel cell division and increase in number in most cancers. It is the first CDK4/6 inhibitor to be approved for the treatment of breast cancer. Pairing palbociclib with other anti-cancer therapies such as endocrine therapy, chemotherapy, and targeted therapy can create a powerful combinatorial effect with real promise for addressing a variety of cancers. Eg amplification of CDK4 is reported in a high percentage of melanomas and esophageal cancers.
Targeted therapy uses medication and other interventions to more accurately identify and attack cancer cells, usually while doing no or little damage to normal cells. “This drug has minor effects on normal cells other than neutrophils ,” said Prof, Peter J. O’Dwyer, MD. “In tumors, it can cause shrinkage, or more commonly, arrest of growth. As we discover new functions for the CDK4/6 target of this medicine, we are likely to use it in combinations to make other anti-cancer agents work better.” In addition to inhibiting the cell cycle, palbociclib has been shown, for example to alter several recently described non-cell cycle functions of CDK4/6, a finding expected to expand its therapeutic role, O’Dwyer added.
Assessing 130 relevant publications in the literature and continuing studies, the all-Penn team found that in addition to its safety and effectiveness in fighting certain types of breast cancer, early trials of palbociclib have shown promise of effectiveness in cases of lymphoma, sarcoma, and teratoma, tumors that while rare, often afflict younger patients.
A phase 2 trial showed that, among 17 patients with previously treated mantle-cell lymphoma, palbociclib resulted in one complete response and two partial responses. Although, median progression-free survival was 4 months, five patients had progression-free survival >1 year. Another phase 2 trial with 29 sarcoma patients treated with palbociclib showed a progression-free survival of 66% at 12 weeks.
Also, combining palbociclib with other anti-cancer agents is feasible, and early results in myeloma and some solid tumors have led to more definitive studies.
In both breast and other cancer trials, palbociclib has been shown to be safe with once-daily dosing, and its main adverse effect is reversible neutropenia. In such cases the drug is temporarily discontinued and reintroduced at a lower dose. Other side effects included fatigue (33 percent), nausea (30 percent), diarrhea (18 percent), constipation (12 percent), and rash (12 percent).
At the recommended doses, evidence of the desired drug effect in tumors has been obtained using novel PET imaging at Penn. These tools can help to individualize patient therapy going forward. http://www.eurekalert.org/pub_releases/2015-12/uops-nbc122915.php
Recent Comments