Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain:1

  • Prospective, multicenter, randomized
  • 200 patients with advanced cancer and refractory pain
  • Patients randomly assigned to receive comprehensive medical management (CMM) or intrathecal drug delivery (IDDS) plus CMM, 100 per arm
  • Intrathecal drug delivery was delivered by the SynchroMed programmable infusion system
  • Entry criteria included Visual Analogue Scale (VAS) pain score of ≥ 5 on a 0-10 scale despite 200 mg/day of oral morphine or its equivalent, or lower doses with intolerable side effects

Demographic and clinical characteristics were well balanced.

Characteristic IDDS Group (n = 101) CMM Group (n = 99)
Age 56.2 ± 13.2 57.8 ± 13.7
Male (%) 51.5% 59.6%
Baseline VAS 7.44 ± 1.97 7.59 ± 1.97
Baseline Composite Toxicity Score** 6.95 ± 4.91 6.65 ± 5.58

** The added scores of all the toxicity scales measured that were related to the treatment.

Type of Cancer and Top 5 Cancer Sites Overall


The data indicate that intrathecal drug delivery plus comprehensive medical management is more clinically effective than CMM alone in treating intractable cancer pain.

During this trial, complications with the infusion system were similar to those seen in clinical use.


Intrathecal drug delivery proved significantly superior to CMM in clinical success:

  • ≥ 20% reduction in VAS scores or
  • Equal scores with ≥ 20% reduction in toxicity

Intrathecal drug delivery patients more often achieved reduction in both pain and toxicity. At 4 weeks after randomization, 60.6% of intrathecal drug delivery system patients, compared to 41.7% of CMM patients, had their pain scores reduced from moderate-severe to mild (VAS < 4). The Smith et al. study of a similar design in 2005 confirmed these results.2

Study Parameter Randomized to IDDS + CMM Randomized to CMM P Values
≥ 20% reduction in Pain VAS or equal VAS with ≥ 20% reduction in mean toxicity score 84.5% (n = 60/71) 70.8% (n = 51/72) 0.05
≥ 20% reduction in both Pain VAS and Toxicity 57.7% (n = 41/71) 37.5% (n = 27/72) 0.02
Mean VAS pain score Reduced 51.5% Reduced 39.1% 0.055
Mean composite toxicity criteria (CTC) scores Reduced 50.3% Reduced 17.1% =.004


All of the measured opioid side effects were reduced more in the IDDS group than in the CMM group.

Significantly larger reductions (p < 0.05) in the IDDS group were noted for fatigue and reduced consciousness.

Reduction in Mean Severity of Side Effects

Graph of Reduced Side Effects With Intrathecal Drug Delivery


Evidence suggests that targeted drug delivery (TDD) for intractable cancer pain is characterized by high initial costs followed by low maintenance costs, whereas conventional medical management (CMM) is associated with steadily increasing, cumulative costs that, over time, can equal the costs of TDD.3,4

In one study, the majority of high expenditures for CMM were attributed transdermal and transmucosal fentanyl products along with ambulatory, patient-controlled IV analgesia.4

  • In contrast, 69% of patients discontinued their systemic opioid pain medications after implantation of the TDD drug infusion system.4
  • Likewise, 72% of patients receiving TDD completely stopped taking fast-onset opioids to control breakthrough pain, instead relying on myPTM.4


Smith TJ, Staats PS, Deer T, et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: impact on pain, drug-related toxicity, and survival. J Clin Oncol. 2002;20(19):4040-4049.


Smith TJ, Coyne PJ, Staats PS, et al. An implantable drug delivery system (IDDS) for refractory cancer pain provides sustained pain control, less drug-related toxicity, and possibly better survival compared with comprehensive medical management (CMM). Ann. Oncol. 2005;16(5):825-833.


Brogan SE, Winter NB, Ablodun A, Safapour R. Therapy for refractory cancer pain: identifying factors associated with cost benefit. Pain Med. 2013;14:478-486.


Hassenbusch SJ. Cost modeling for alternate routes of administration of opioids for cancer pain. Oncol. 1999;13(5 suppl 2):63-67.