(13-09-10) Bisphosphonates Tied to Esophageal Cancer

Note that this study has found that esophageal cancer may be more common in
patients taking oral bisphosphonate drugs for long periods.


Note also that as pointed out by the editorialist, if causality is proven, the
incidence in the population would still be relatively low. Nevertheless, it
would be prudent to reinforce recommended directions for taking the product
with each prescription.
A second look at British registry data indicates that esophageal cancer may be
more common after all in patients taking oral bisphosphonate drugs for long
periods.
In a nested case-control analysis involving some 80,000 patients tracked for
more than seven years on average, individuals diagnosed with esophageal cancer
of were 1.93 times as likely (95% CI 1.37 to 2.70) to have received at least 10
prescriptions for oral bisphosphonates, compared with controls not having
cancer, reported Jane Green, MD, DPhil, of the University of Oxford in England,
and colleagues online in BMJ.

The likelihood of receiving at least one bisphosphonate prescription among
esophageal cancer patients was 1.30 (95% CI 1.02 to 1.66) relative to controls,
the researchers found.

The findings were especially remarkable because another research group
conducting a case-control study of the same registry -- Great Britain's General
Practice Research Database, containing records on some six million patients --
recently reported no increase in esophageal cancer rates in patients treated
with bisphosphonates.

Green and colleagues explained the discrepancy by noting that mean observation
time prior to diagnosis in the other analysis was substantially shorter, 4.5
versus 7.7 years.

Also, they noted, their study used five matched controls for each case,
whereas the earlier study had equal numbers of cases and controls.

Our study thus had the potential to include people with longer durations of
bisphosphonate use and also had greater statistical power, Green and colleagues
asserted.

An accompanying editorial by an FDA epidemiologist, Diane Wysowski, PhD, noted
that links between bisphosphonates and esophageal cancer have been proposed for
more than 15 years. (The editorial carried a disclaimer that it did not
necessarily express the agency's official view.)

The FDA has collected a total of 68 case reports of esophageal cancer in
patients taking bisphosphonates, half in the U.S. and the rest in Europe and
Japan, but has not ordered label warnings. Prescribing information for oral
bisphosphonates does include information on risks of other esophageal effects
such as erosions and strictures, and dosing instructions are geared toward
speeding the drugs through the esophagus.

The suggestion of a connection between these agents and esophageal cancer have
prompted efforts at systematic research, including the new study.

Green and colleagues examined records of 2,954 patients with esophageal
cancer, 2,018 patients with stomach cancer, and 10,641 with colon cancer, along
with five controls for each of these cases matched for age, sex, observation
time prior to diagnosis, and practice location.

About 3.1% of the esophageal cancer patients had received at least one
bisphosphonate prescription before diagnosis, compared with 2.4% of the
controls over a similar period (relative risk 1.30 after adjusting for smoking
status, alcohol intake, and body mass index).

Rates of bisphosphonate use were similar in the stomach and colon cancer
patients relative to controls, the researchers found.

In the esophageal cancer patients, the relationship with bisphosphonate use
appeared to strengthen with the number of prescriptions and with the estimated
duration of use.

Green and colleagues calculated a relative risk of 1.93 for receiving at least
10 prescriptions in cases versus controls, whereas esophageal cancer patients
had virtually the same likelihood of receiving one to nine prescriptions as
controls (RR 0.93, 95% CI 0.66 to 1.31).

Similarly, estimated duration of use (based on the distribution of
prescriptions over time) of at least three years was linked to esophageal
cancer with a relative risk of 2.24 (95% CI 1.47 to 3.42), but shorter duration
was seen in about equal numbers of cases and controls.

These patterns were also not seen in the stomach or colorectal cancer
patients.

The association [in esophageal cancer patients] did not vary materially within
subgroups defined by age, sex, smoking status, alcohol drinking, or body mass
index; diagnosis of osteoporosis, previous fracture, or previous upper
gastrointestinal disease; or prescription of nonsteroidal anti-inflammatory
drugs, corticosteroids, or acid suppressant drugs, Green and colleagues added.

But the researchers stopped short of concluding that bisphosphonate treatment
contributes to esophageal cancer, noting that they could not rule out the
possibility that the associations observed reflect other, unknown, factors that
are linked to prolonged use of bisphosphonates and that also increase the risk
of esophageal cancer.

Other limitations included the lack of data on the extent to which patients
used drugs prescribed to them or on prescriptions received before entry into
the database.

in the editorial, Wysowski didn't take a position on whether there is a causal
link, noting that the evidence remains divided and weak. Even if there is such
a connection, she wrote, the incidence in the population would be expected to
remain relatively low.

Still, she suggested that physicians consider the possibility of risk when
prescribing the drugs and, when talking to patients, reiterate the importance
of following the label directions for taking these drugs, which minimize the
drugs' direct contact with the esophageal tract.

Wysowski also recommended that doctors urge patients to report difficulty
swallowing or other gastrointestinal symptoms promptly.

The UK Medical Research Council and Cancer Research UK provided funding for
the database project and the current analysis.

Study authors and the editorialist declared they had no competing financial
interests.


Primary source BMJ
Source reference
Green J, et al Oral bisphosphonates and risk of cancer of oesophagus, stomach,
and colorectum case-control analysis within a UK primary care cohort BMJ 2010;
DOI 10.1136bmj.c4444.

Additional source BMJ
Source reference
Wysowski D, Oral bisphosphonates and oesophageal cancer BMJ 2010; DOI 10.1136
bmj.c4506.

News

---

In evidenza

"L'informazione presente nel sito serve a migliorare, e non a sostituire, il rapporto medico-paziente."

Per coloro che hanno problemi di salute si consiglia di consultare sempre il proprio medico curante.