What is the evidence for implantable drug delivery systems for refractory cancer pain?

Despite best management, 14% of patients with cancer have unrelieved pain and many more have undesirable side effects from pain medicines. Intrathecal implantable drug delivery systems (IDDSs) manage intractable cancer pain by delivering pain medications directly to the spinal fluid. In addition to data from many nonrandomized trials, there are now randomized clinical trial data showing better clinical success, pain relief, drug toxicity control, and perhaps survival compared with comprehensive medical management (CMM). We reviewed published cohort reports from 1980 through 2003 using Medline. We studied 202 patients with unrelieved pain on visual analogue scale (VAS) pain scores of >/= 5 on a scale of 0-10 despite conventional management. The main outcome measure was clinical success, defined as a 20% improvement in pain control and composite drug toxicity. We ranked the trials according to accepted levels of evidence. The nonrandomized trials all showed pain relief with acceptable complication rates, but often did not have standardized assessment schemas, had no control groups, and were single-institutional trials. In the randomized trial, more patients had clinical success with IDDS (84.5%) than with CMM (70.5%, P < 0.05). After 4 weeks, the mean VAS pain score decreased from the baseline of 7.75 to 4.74 (39% reduction) in the CMM group and from 7.45 to 3.59 (52% reduction) in the IDDS group (P = 0.057). The drug toxicity scores decreased from the baseline of 6.35 to 5.18 (19% reduction) in the CMM group and from 7.14 to 3.46 (52% reduction) in the IDDS group (P = 0.01). All individual toxicities were improved more by IDDS, especially fatigue and depressed level of consciousness. Patients randomized to IDDS therapy had improved survival, with 53.9% alive at 6 months compared with 37.2% of the CMM group (P = 0.06). There is now high-level randomized clinical trial evidence, in addition to consistent nonrandomized evidence, that IDDSs reduce pain and common drug toxicities and are associated with improved survival. Added to the multiple cohort studies, the evidence is compelling in favor of IDDS.