But early believers pressed on, confident that the regimens could be fine-tuned, the toxicities tamed. In time, dramatic advances were made in dosages and treatment regimens, in combining chemotherapeutic agents and in using them in various ways with surgery, radiation, and biologic therapies. A better biologic understanding of cancer led to more precise targeting of chemotherapy. And progress was made in treating the side effects that once seemed to be chemotherapy's death knell, a point illustrated by Dr. Schilsky.
The experts consulted for this article have conducted research for pharmaceutical companies that manufacture various forms of chemotherapy.
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Future of Cancer Treatment Includes Chemotherapy
People have been trying to write the epitaph for chemotherapy virtually since nitrogen mustard was approved in 1949. But the naysayers were shortsighted then, and still are today, a number of leading oncologists maintain.
For all the talk of “targeted” therapy taking center stage in cancer therapy, “chemotherapy is likely to be an important part of cancer treatment for some time to come,” Dr. Schilsky said.
The belief that chemotherapy is too toxic, and therefore should be replaced by “targeted therapy,” negates several truths; one, that chemotherapy isn't “targeted,” and two, that molecular-targeted therapies such as biologics and immunotherapy are capable of curing the solid tumors that afflict most patients with cancer.
“Methotrexate and 5-fluorouracil are among the most targeted drugs we've ever had,” Dr. Schilsky said. “They're more than 50 years old and have not been replaced.”
Although agents designed to target characteristics unique to tumor cells may be the hope of the future, to date they have matched chemotherapy's success only in a few rare tumor types, he added.
Empiric studies of early chemotherapeutic drugs may look “pretty unsophisticated” today, but the signals that resulted were strong, Dr. Muggia agreed. “There's no one way,” he said, predicting that chemotherapy will long play a key role in combination regimens that also may include molecular-targeted agents.
“As we get into targeted therapy, there are some problems with that as well,” he added.
Dr. DeVita echoed the notion that “targeted therapy is chemotherapy.”
“We always hoped, over time, that chemotherapy would become more specific and it has,” he said. “Nitrogen mustard was the first use of systemic therapy based on the premise that treatment failure was due to circulating cancer cells. All subsequent systemic therapy, including biologics, is based on that premise.”
Progress in cancer therapy, then, is likely to build on lessons of the past and encounter hurdles not foreseen, Dr. DeVita said.