SAN FRANCISCOA trial to compare comprehensive medical
management (CMM) to CMM plus intrathecal morphine delivery via an implantable,
programmable drug delivery system (IDDS) showed that the pump improved pain
control by more than 15% and reduced medication side effects by nearly 50%.
"The pump not only improved pain control and quality of life in patients
with otherwise intractable cancer-related pain," Thomas J. Smith, MD, one
of the study chairmen, told ONI, "but reduced costs associated with
medication and side effects so much that by the third month of treatment,
intrathecal morphine delivery should become cost-effective compared to the high
doses of oral morphine typically used in these patients."
Dr. Smith noted that the data were still preliminary. He is
chairman of the Division of Hematology/Oncology, Medical College of Virginia
Hospitals, Virginia Commonwealth University, Richmond, VA. The study was
sponsored by Medtronic.
More than 150 of a planned 200 patients have been enrolled in
this first randomized, prospective trial comparing CMM to CMM plus intrathecal
morphine administration via the Medtronic SynchroMed pump. Dr. Smith presented
preliminary data from 22 patients originally randomized to the CMM arm who
subsequently crossed over to the IDDS arm due to intractable pain.
"Since these patients represent the hardest of pain
control challenges, we analyzed their response to see if IDDS could relieve
their pain," Dr. Smith explained. "All failed pain control or
suffered excess side effects on CMM. All centers followed the Agency for Health
Care Policy and Research Cancer Pain Relief Guidelines, and all crossovers were
Pain was measured using a visual analog scale (VAS) of 0 to 10.
Opioid toxicity was measured using the National Cancer Institute Common
The average VAS pain score at crossover (6.33 ± 2.76)
decreased more than 28% by 1 month after crossover. Toxicity decreased more
than 29%. Overall quality of life and caregiver quality of life were similar
before and after crossover:
Dr. Smith said that survival after crossover to IDDS was
greater than or equal to 3 months, within the range where IDDS can be cost
saving compared to conventional medical management in most of the 22 patients.
Some Still Hurting
Study data also show that pain management still leaves some
patients suffering despite massive doses of morphine, in both US and European
medical centers. The trial also provides a "snapshot" of current pain
management for the 10% to 15% of patients not controlled with standard
treatment, Dr. Smith noted, adding that the picture is not pretty.
Study physicians predicted overall survival of 10 months, but
actual survival was only 3 to 4 months. Neuropathic pain was more common than
expected: 59% of patients had mixed neuropathic and nociceptive pain, and an
additional 15% had primarily neuropathic pain. Despite use of a mean 880 mg/day
of morphine or equivalent, the baseline VAS pain scores were over 7 (on a 0 to
Patients whose pain was not adequately relieved by opioids were
using an average of more than 1,200 mg/day at study entry. Baseline quality of
life and caregiver quality of life scores were low on both arms, with an
average of 3 major toxicities. Most patients were using adjuvant medicines,
more so in European (68%) than US (53%) centers.
Patients in both study arms had substantial improvements in
pain control while in the study, according to Dr. Smith. "Treatment with
intrathecal morphine also sustained these patients’ quality of life at a
point in disease progression when quality of life usually declines," Dr.
Preliminary data suggest that there is a substantial burden of
unrelieved pain in cancer patients despite massive doses of opioids and
multiple adjuvant medicines and that morphine administered via an implantable
pump can improve pain control for many of these patients. "Early results
from this research should encourage more oncologists to consider using
implantable programmable drug pumps for intrathecal infusion of morphine to
treat patients who continue to experience intractable pain even after
traditional pain management," Dr. Smith said. Final study results are
expected early in 2002.