83% of US cancer doctors say they have faced oncology drug shortages and, of those, nearly all say that their patients' treatment has been impacted, a new study reports.

The results show that shortages - which have hit especially hard among drugs to treat paediatric, gastrointestinal and blood cancers - have left physicians surveyed unable to prescribe standard chemotherapies for a range of cancers, say the researchers, from the Abramson Cancer Center and the Perelman School of Medicine at the University of Pennsylvania.

Results of the study - the largest of oncologists to quantify the toll of the US cancer drug shortage to date - indicate that the vast majority of cancer doctors "are facing wrenching decisions about how to allocate lifesaving drugs when there aren't enough to go around," said the study's senior author, Dr Kerthi Gogineni.

"The potential impact of these drug shortages is vast - they are putting patients at risk and driving up costs of cancer care," she added.

The study also finds that oncologists have adapted in a variety of ways when preferred or recommended drug are scarce. For example: - 78% report treating patients with a different drug or drug regimen; - 77% have substituted different drugs part-way through therapy; - 43% have delayed their patients' treatment; - 37% have had to choose among patients who needed a particular drug; - 29% have omitted doses and 20% reduced doses; and - 17% have referred patients to another practice.

So far, little is known about how these adaptations may impact clinical outcomes, but the authors say the widespread treatment delays reported underscore the urgency of the problem. Dr Gogineni points out that the most risky types of modifications occur when physicians substitute drugs part-way through treatment, as there is often no established dose equivalence or known safety profile when the substitute is combined with other therapies.

Clinical trials are also hampered when drugs necessary for properly testing new regimens are scarce; the team found that nearly 12% of the time, drug shortages prevented enrolment in studies, delayed administration of a study drug or suspended involvement of patients in clinical trials.

The authors also point to the substantial cost burden imposed by drug shortages. They find that generic drugs tend to be the most difficult to obtain, sometimes because of manufacturing problems but often due to decisions by drugmakers to deprioritise production because of the slim margin on generics, they say.

Consequently, when confronted with a shortage, oncologists substitute more expensive branded drugs 60% of the time. In some cases, these swaps increase costs of care exponentially; for example, 22% of doctors said they had to substitute the generic intravenous chemotherapy drug 5-fluorouracil (5-FU) with capecitabine (Roche's Xeloda), an oral equivalent that is metabolised into 5-FU in the body.  Capecitabine is a branded drug and costs around 140% as much as 5-FU for one round of colon cancer treatment, they say.

Despite the prevalence of the shortage issues, 70% of doctors told the survey that their cancer centres or practices had no formal guidance for making allocation decisions. This raises difficult questions for doctors, such as: - should a patient on a clinical trial get priority for a drug, or should a patient receiving standard therapy take precedence? Do patients with early-stage cancer who are being treated with curative intent get drugs first, or should they go to patients with metastatic disease who need chemotherapy to keep their disease from spreading further?

"This is a dynamic problem, and when we learn about new shortages on the horizon, there is usually not a lot of time to plan on how to deal with them," said Dr Gogineni.

"Guidelines must be rapidly updated and disseminated, both to large academic medical centres and smaller community hospitals and practices, where the majority of cancer care is delivered and which often lack the bulk-buying power to keep scarce drugs in necessary supply," she added.