New breast cancer drug may be effective against other types of cancer

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 additional original research conducted by experts at the Abramson Cancer Center (ACC) in the University of Pennsylvania published this month in JAMA Oncology.

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.

"All living cells undergo cell division and palbociclib's unique capacity to halt the cell division process (also known as the 'cell cycle') therefore has potentially broad applicability," said the study's lead author Amy S. Clark, MD, MSCE, an assistant professor of Hematology/Oncology at Penn's Perelman School of Medicine and ACC. "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." For example, 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 (white blood cells)," said the study's senior author, Peter J. O'Dwyer, MD, a professor of Hematology/Oncology at Penn and director of the Developmental Therapeutics Program at the ACC. "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, as well as interpreting their own 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 four months, five patients had progression-free survival greater than one year. Another phase 2 trial with 29 sarcoma patients treated with palbociclib showed a progression-free survival of 66 percent 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, an abnormally low count of neutrophils, a type of white blood cell that helps fight infections. The lower their neutrophil count, the more vulnerable patients are to infectious diseases. 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.

Other Penn co-authors are Thomas B. Karasic, MD; Angela DeMichele, MD, MSCE; David J.Vaughn, MD; Mark O'Hara, MD; Rodolfo Perini, MD; Paul Zhang, MD; Priti Lal, MD; Michael Feldman, MD, PhD; and Maryann Gallagher, RN.

The study was funded by Pfizer Inc and the National Institutes of Health (5P30 CA16520-25).

Most Popular Now

FDA approves drug to treat ALS

The U.S. Food and Drug Administration today approved Radicava (edaravone) to treat patients with amyotrophic lateral sclerosis (ALS), commonly referred to as Lou Gehrig's...

Read more

FDA approves first cancer treatment for any solid …

The U.S. Food and Drug Administration today granted accelerated approval to a treatment for patients whose cancers have a specific genetic feature (biomarker). This is th...

Read more

Sanofi and Regeneron announce FDA Approval of Kevz…

Sanofi and Regeneron Pharmaceuticals, Inc. have announced the U.S. Food and Drug Administration (FDA) approval of Kevzara® (sarilumab) for the treatment of adult patients...

Read more

AstraZeneca marks a key milestone with the ‘toppin…

AstraZeneca marks a key milestone in its successful move to Cambridge, UK, with the 'topping out' of its new, state-of-the-art, strategic R&D centre and global corporate ...

Read more

FDA approves first treatment for a form of Batten …

The U.S. Food and Drug Administration today approved Brineura (cerliponase alfa) as a treatment for a specific form of Batten disease. Brineura is the first FDA-approved ...

Read more

Abbott announces CE Mark and first use of the worl…

Abbott (NYSE: ABT) today announced CE Mark and first use of the new Confirm RxTM Insertable Cardiac Monitor (ICM), the world's first smartphone compatible ICM that will h...

Read more

Imfinzi significantly reduces the risk of disease …

AstraZeneca and MedImmune, its global biologics research and development arm, today announced positive results for the Phase III PACIFIC trial, a randomised, double-blind...

Read more

Antibiotic doxycycline may offer hope for treatmen…

A study published in the journal Scientific Reports suggests that doxycycline, an antibiotic used for over half a century against bacterial infections, can be prescribed ...

Read more

Novartis exercises exclusive option agreement with…

Novartis announced today that it has notified Conatus Pharmaceuticals Inc., of its exercise of the option to an exclusive license for the global development and commercia...

Read more

England's Cancer Drugs Fund 'failed to deliver mea…

Analysis of the drugs that were approved for use by the NHS Cancer Drugs Fund (CDF) in England has shown that the fund was not good value for patients and society and may...

Read more

High levels of exercise linked to nine years of le…

Despite their best efforts, no scientist has ever come close to stopping humans from aging. Even anti-aging creams can't stop Old Father Time. But new research from Brigh...

Read more

Vitamin A deficiency is detrimental to blood stem …

Many specialized cells, such as in the skin, gut or blood, have a lifespan of only a few days. Therefore, steady replenishment of these cells is indispensable. They arise...

Read more

Pharmaceutical Companies

[ A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Z ]