Franco Muggia, MD
When Franco Muggia, MD, was a freshly minted oncologist 50 years ago, his new colleagues warned him not to waste much time learning about a drug like fluorouracil. After all, they suggested, the chemotherapy agent would soon be a thing of the past.
“They were wrong—it’s still around,” Muggia, professor of Medicine (Oncology) at the NYU School of Medicine in New York City and medical director of the Chemotherapy Foundation, says now. “It does have some special features that make it particularly selective against GI cancers, which are a breed of their own.”
The drug’s persistence is a prime example of the continuing role of chemotherapies as a backbone of cancer management, even as novel targeted drugs and immunotherapies are increasingly introduced into treatment paradigms for a variety of tumor types, said Muggia. In fact, he noted, a number of new chemotherapies have been introduced within the last 10 to 15 years, several of them practice changing.
Among Muggia and his colleagues, the expectation is that these new drugs, as well as older chemotherapy standbys, will be used into the foreseeable future, whether alone, in combination, or sequenced with novel targeted agents or immunotherapies. So an important goal, they told OncologyLive, is to find safer, more targeted ways of delivering chemotherapy.
A method that’s gathering speed is the development of antibody-drug conjugates (ADCs), which pair extremely strong chemotherapy drugs with antibodies that target cancer cells.
Recent Innovations in Modality
One important chemotherapy that emerged about a decade ago is oxaliplatin (Eloxatin), whose approval as a frontline treatment in 2004 “totally changed the results in colorectal cancer,” Muggia pointed out. Approved in 2008, bendamustine hydrochloride (Treanda), which is “revolutionizing the treatment of some lymphomas,” is a new formulation of the first chemotherapy ever, nitrogen mustard, proving that it’s an oversimplification to consider chemotherapy outdated, he said.
Muggia added that chemotherapy regimens are “making a dent” in extremely difficult-to-treat pancreatic cancers, and that single-agent chemotherapies (cisplatin and methotrexate, respectively) can cure testicular cancer and choriocarcinoma.
“Certainly, treatment is multidisciplinary,” said Muggia. “When used by itself, it’s a tall order to expect a chemotherapy to eliminate every single cancer cell in somebody who presents with very advanced disease. So when using systemic therapies, we often have to work with surgery, with radiation, and, more and more nowadays, the great advances being made in immunology. No one area should be emphasized or de-emphasized. Those involved in the study of human disease and its treatment don’t get hung up on the semantics of what a class of therapy is called, but follow what are the best leads.”
Debu Tripathy, MD
In fact, the difference between chemotherapies and targeted agents is not always clear cut, added Debu Tripathy, MD, professor of Medicine and co-leader of the Women’s Cancer Program at the USC Norris Comprehensive Cancer Center in Los Angeles.
“We tend to make a distinction between targeted and chemotherapy drugs, but the line that separates those is a little bit blurry,” he said. “Chemotherapy drugs have certain properties of biological drugs and can modulate cellular pathways, and, similarly, targeted drugs can cause injury to normal cells, so they have some properties of chemotherapy.”
A movement away from cytotoxic therapies is anticipated in hematologic malignancies. Chemotherapy has been eliminated from the standard regimen for chronic myeloid leukemia (CML), and promising experimental agents could make the same outcome possible in other blood cancers, said Bruce Cheson, MD, professor of Medicine at the Lombardi Comprehensive Cancer Center at Georgetown University in Washington, DC.
But chemotherapies are curative—and thus, for now, indispensable—in diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma, he noted. In breast, lung, and prostate cancers, leading oncologists not only rely on chemotherapy as a staple of treatment regimens, but also expect it to remain part of the armamentarium for the foreseeable future.
Among them is Naiyer Rizvi, MD, a lung cancer expert at Memorial Sloan Kettering Cancer Center in New York City.