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New Evidence Supports the Use of Intrathecal Drug Delivery in Cancer Pain Care

Although the efficacy of intrathecal drug delivery for cancer-related pain is well established, it remains underutilized. New data confirm that it is a safe and effective alternative to systemic opioid use.

Despite guidelines supporting pain management as an important means of improving quality of life in patients with cancer,1,2 acceptable analgesia remains out of reach for a significant number of patients. Moreover, as five-year survival rates for all cancer types increase, as many as one-third of survivors experience chronic pain and may need long-term opioid analgesia.3

Even with current concerns about excessive opioid use, referral to a pain specialist may allow a patient to benefit from a complex pharmacologic management strategy or interventional technique. One of these, the use of intrathecal drug delivery systems (IDDS), administers morphine directly to the spinal cord, using an implanted drug delivery system with a refillable reservoir and fully programmable functionality. Patients receive continuous medication while maintaining the ability to control breakthrough pain orally.

The benefits of intrathecal therapy may extend beyond pain control, including reduced serum opioid levels and improved bowel function, fatigue, and immune function. (Image: iStock)

IDDS May Impact Pain Control, Drug Toxicity, Fatigue, and Immune Function

Studies of IDDS have demonstrated success in pain control, drug toxicity, and improved survival in patients with refractory cancer pain compared to conventional medical management. A recently published analysis of a multicenter registry supplements existing clinical trial data that support IDDS as a safe and effective therapeutic option with a positive benefit-risk ratio in the treatment of cancer pain.4

Led by researcher Lisa M. Stearns, MD, of the Center for Pain and Supportive Care in Phoenix, this prospective, long-term, registry enrolled 1,403 patients from 2003 through July 2017. The most frequent cancer types were lung, breast, colon/rectal, pancreatic, and prostate. Most patients (87%) were followed through death, although 4.3% exited because of device explant or therapy discontinuation, and the remaining 8.6% discontinued for other reasons related to follow-up.4

Pain scores for those providing baseline and follow-up data improved significantly at 6 and 12 months (P = 0.0007; n = 103 and P = 0.0026; n = 55, respectively). Infections requiring surgical intervention, such as for IDDS explant or replacement, pocket revision, irrigation and debridement, were reported in 3.2% of patients.4

The benefits of intrathecal therapy may extend beyond pain control. In another recent study, intrathecal therapy was associated with a marked reduction in  serum opioid levels, almost to the point of being undetectable.5 According to lead investigator Shane E. Brogan, MB BCh, at the University of Utah in Salt Lake City, reducing serum opioid concentrations may also restore bowel function, improve fatigue, and positively impact immune function.5

 

Intrathecal Doses are a Fraction of Oral or Transdermal Doses, Not to Mention Costs

Intrathecal multimodal therapy is based on the principle that combining drugs with different mechanisms of action produces a synergistic effect on pain reduction, has a drug-sparing effect, and reduces the incidence of adverse effects. The commonly used IDDS drug ziconotide, for example, is often combined with morphine to produce a more widespread blockade of synaptic transmission from cells bearing N-type calcium channels than is possible with morphine alone.7

In addition, with IDDS, small doses can result in a robust analgesic effect on spinal cord and nerve root receptors while eliminating or minimizing systemic toxicity.6

In a recently published study of patients with end-stage cancer-related pain refractory to high doses of oral or transdermal opioids, 60 adult patients received an intrathecal combination of morphine, ziconotide, and levobupivacaine.7 Before enrollment, patients received a mean daily dose of 240 ± 80 mg morphine equivalent, but all had poorly controlled pain or adverse events related to high doses of opioids, or both.

The initial mean daily doses were 0.8  ±0.3 mg morphine, 1.2 mcg ziconotide, and 3 mg levobupivacaine. At Day 2, pain scores measured on a visual analogue scale from 0 to 100 decreased from 88 ± 20 to 49 ± 17 (P<0.001). This reduction persisted to 56 days, with mean scores of 44 ± 9 (P > 0.001). At that point, mean daily doses were 2 ± 1 mg morphine, 2.8 ± 1 mcg zoconotide, and 3.8 ± 2 mg levobupivacaine. Very few adverse effects were observed, and patient satisfaction was extremely high during the study period.7

Lead investigator Filomena Puntillo, MD, of the University of Bari in Italy, concluded, “Patient satisfaction was surprising. Although they were afraid of the invasiveness of the treatment and of the limitation of mobility due to the external pump, good pain control overcame all their fears.”7

Compared to conventional medication management, IDDS-treated patients have had lower utilization and total medical costs in the first year after implantation, which were the result of savings in hospitalization and emergency department visits. In a recent retrospective claims analysis, savings of $15,142 (P = 0.0097) at two months and $63,498 (P=0.03) at 12 months were achieved after starting IDDS compared to CMM.8

 

Perceived Risks and Patient Acceptance

Given the improvements in pain control and reductions in cost, why is IDDS not more widely accepted?

Patients enrolled in the registry had a median time between cancer diagnosis and IDDS therapy of more than 2 years, which likely reflected the duration of poorly controlled pain. According to lead researcher Dr. Stearns, “perceived risks associated with implantation and management have been identified as a limiting factor in therapy acceptance, and a possible reason for the delayed referral to pain physicians for treatment after cancer diagnosis.”4

Yet in this registry, IDDS risks compare favorably to those associated with placement of intravenous ports for medication delivery.

In another review, the rate of surgical site infections following IDDS placement in 217 patients undergoing frequent concurrent antineoplastic therapy and leukopenia in the perioperative period was 0.9% (95% CI, 0.1% to 3.3%).9

As long-term evidence for the benefits of intrathecal drug delivery accumulates, “adequate and improved pain control in patients with cancer, even in advanced stages, with concurrent quality-of-life maintenance are attainable,” concluded Dr. Stearns.4

Last updated on: September 21, 2020
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Management of Intrathecal Therapies by Interprofessional Teams
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