By: Richard Pazdur, M.D.
I was in the third grade in the early 1960’s when my mother hung up the receiver of our old rotary dial telephone on the kitchen wall and broke down in tears. Dorothy, the mother of my close friend Fred, had just died of breast cancer. Dorothy and my mother worked together on various PTA and Cub Scout projects at my elementary school in Calumet City, a southeast suburb of Chicago. When my mother ended the phone call, she lamented “if only she received Krebiozen.”
Dorothy was a proud, tall woman with jet black hair, wearing it upswept in a bun, and always appearing with bright red lipstick. She had undergone all the medical therapies available in the early 1960’s for advanced breast cancer, which would appear primitive in the light of today’s advances – including the now infamous Halsted radical mastectomy, large doses of searing cobalt radiation therapy, and surgery to remove her ovaries and adrenal glands to control painful bone metastases.
In discussing Krebiozen years later with my mother, she noted that Dorothy had received chemotherapy drugs. The doctors “had just given up on her” since the drugs didn’t work and there was “nothing else to do and that’s why she wanted to try Krebiozen.”
In the late 1950’s and early 1960’s, Krebiozen was touted as an active drug for cancer, especially in Chicago. The drug, initially developed from the blood of horses that had been injected with bacteria, was touted in written articles by a University of Illinois researcher extolling its benefits as an anti-cancer drug. Dozens of patients provided testimonials about the drug’s benefits to local media. My mother heard these accounts and desperately wanted my friend’s mother to have access to this promising, yet unproven drug: “she’s a young mother and is leaving behind two small children.”
Years later, I still frequently recall this story and its lessons. Patients with cancer, especially those who have exhausted currently available treatment options, and their friends and families search for a drug, possibly a drug that is not yet FDA-approved, and are willing to “take chances” in the hope that it may work. However, access to unapproved drugs needs to be balanced with both the protection of patients against a drug that may ultimately prove to be ineffective, and the need for clinical trials. These trials will demonstrate the drug’s safety and efficacy, ensuring a foundation for the drug’s use for future patients.
In 1987, the FDA first established rules that allowed patients with serious and life-threatening diseases access to investigational drugs outside of clinical trials, even though the safety and effectiveness of the drug has not been fully established. In August 2009 FDA changed its rules to clarify and broaden them for patients and treating physicians. This is often referred to as “expanded access.”
Expanded access refers to the use of an investigational drug when the primary purpose is to treat a patient rather than to obtain information about the drug that is generally derived from clinical trials. There are different types of expanded access programs, ranging from single patient access to those providing access to hundreds or even thousands of patients. Information regarding the unapproved drug’s safety and efficacy required for use in a single patient is far less than information for trials that might provide access to hundreds of patients.
Some patients, who have not received standard therapies, especially if those therapies have been shown to improve survival, may not be candidates to receive unapproved drugs through an expanded access program. FDA has coordinated educational efforts with the American Society of Clinical Oncology (ASCO) to educate health care professionals and patients regarding appropriate patients for expanded access programs, as well as procedures to obtain expanded access to unapproved drugs.
Patients and healthcare providers seeking expanded access to unapproved drugs need to understand that drug companies must agree to provide these drugs to patients. FDA cannot mandate or require a drug company to provide an unapproved drug to patients. In fact, FDA oncologists have agreed with patients and their physicians that an unapproved drug could be used, only to find later that a drug company is unwilling to provide the drug.
There are a variety of explanations that drug companies have offered for not providing patients expanded access to promising, yet unapproved drugs. These include cost, the perception that this access would interfere with the drug’s development and approval, or simply “corporate policy.” Other issues may be more opaque and involve manufacturing problems that companies may be unwilling to disclose and FDA cannot publicly comment on, in the context of an unapproved drug.
In June, ASCO will be holding its annual conference and many abstracts will probably provide preliminary data on breakthrough drugs for patients with limited treatment options. Many patients will believe they cannot wait for the drug’s further development or its approval. FDA has provided clear guidance on the appropriate avenues to access promising, yet unapproved drugs; however, the success of these programs depends on the alignment of the FDA, an informed patient and healthcare provider, and ultimately, a willing drug company.
Whatever happened to Krebiozen? A 1973 review by an independent committee of 24 scientists of over 500 “best cases” found it had no anti-cancer activity. The NCI director at the time noted “….from a scientific standpoint we regard the case closed.”
Richard Pazdur, M.D., is the Director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research