IDDS and SCS: Exploring Multimodal Approaches for Managing Cancer Pain
Cancer pain is associated with low QoL, increased depression risk, and reduced tolerance to cancer treatment.
Cancer-related pain affects approximately 9 million people worldwide each year, with the number of new cases expected to increase from 12.7 million in 2008 to 22.2 million by 2030.1,2 Cancer pain has been linked to reduced quality of life, increased risk for depression, and reduced tolerance to cancer treatment.3
The management of cancer pain is gradually shifting from a stepwise approach to a multimodal approach that includes the early implementation of interventional pain procedures. A review published in Current Pain and Headache Reports examines the evidence and current practices pertaining to 2 such procedures: intrathecal drug delivery systems (IDDS) and spinal cord stimulation (SCS).3
Intrathecal drug delivery systems
Intrathecal vs systemic drug delivery offers the advantages of requiring lower drug doses, being associated with fewer adverse effects, being more (cost-)effective, and being less toxic. In addition, IDDS does not interfere with chemotherapy or radiotherapy.
Intrathecal therapy is typically indicated for patients who have not adequately responded to conventional pharmacologic treatment, or those for whom these treatments are associated with adverse effects. The review authors noted that although results of numerous studies indicate benefits of IDDS for cancer pain, the quality of the evidence is generally low because of small sample sizes or flaws in methodology.
Although morphine and ziconotide are the only analgesic agents approved by the US Food and Drug Administration for intrathecal therapy, "the off-label use of hydromorphone and sufentanil in combination with adjuncts such as bupivacaine, baclofen, and clonidine inside the intrathecal space are largely accepted by expert consensus" for cancer pain management, they reported.
Morphine. In a randomized clinical trial published in 2002, intrathecal delivery of morphine and comprehensive medical management were examined in 202 patients with refractory cancer pain receiving a 200 mg/day oral morphine regimen.4 Patients receiving intrathecal morphine vs comprehensive medical management reported improvements in visual analog scale (VAS) pain scores (reduction of 3.90 vs 3.05, respectively) and medication-related fatigue and sedation, and had improved toxicity scores (50% vs 17% reduction, respectively) and 6-month survival (53.9% vs 37.2%, respectively).
In prospective studies, intrathecally delivered combinations of medications, such as morphine/ropivacaine and baclofen/clonidine, were found to improve refractory cancer pain. In a double-blind crossover study, morphine-sparing effects were observed when dexmedetomidine was combined with morphine, with no serious adverse effects reported.5
"Overall, there are insufficient human studies supporting the use of intrathecal octreotide, neostigmine, adenosine, baclofen, clonidine, midazolam, and ketamine for cancer pain although experts recommend their use (with the exception of dexmedetomidine and adenosine) should first-line medications fail to produce sufficient analgesia," the review authors stated.
Ziconotide. A randomized placebo-controlled trial examined the effects of intrathecal ziconotide in 95 patients with cancer and 13 patients with AIDS, all with refractory pain (ie, VAS pain intensity score [VASPI] >50 mm despite prior treatment with systemic and/or intrathecal analgesics).6 Patients receiving ziconotide vs placebo had greater improvements in VASPI scores (53.1% vs 18.1%, respectively; P <.001), and a higher percentage of patients reporting serious adverse events (30.6% vs 10.0%, respectively).
In a randomized trial of patients with noncancer pain, the slow titration of ziconotide during a 3-week period vs placebo was associated with greater improvements in VASPI scores (14.7% vs 7.2%, respectively) and comparable prevalence of adverse effects, suggesting this approach may mitigate the elevated rates of adverse effects previously observed with ziconotide.7
Ongoing studies investigate the intrathecal delivery of novel analgesic agents, including AYX1, an inhibitor of transcription factor EGR1; resiniferatoxin, a capsaicin analog that targets the TRPV1 receptor; and other conopeptides in addition to ziconotide, including MrVIB, pyroglutamate-1-MrIA, and Con-G.