ORLANDO-Randomized clinical trial data presented at the 38th Annual Meeting of the American Society of Clinical Oncology (abstract 1436) show that pain control medications delivered through an implantable intrathecal drug delivery system (IDDS) are significantly more effective than similar drugs given as oral or injectable formulations.
ORLANDORandomized clinical trial data presented at the 38th Annual Meeting of the American Society of Clinical Oncology (abstract 1436) show that pain control medications delivered through an implantable intrathecal drug delivery system (IDDS) are significantly more effective than similar drugs given as oral or injectable formulations.
Lead investigator Thomas J. Smith, MD, who presented the study as a poster at the meeting, told ONI: "Oncologists should start thinking about intrathecal drug delivery systems any time cancer patients have severe pain. Compared to comprehensive medical management, we found that the IDDS reduced pain scores by 52% and reduced drug side effects by one third." The improvement in drug-related side effects was particularly apparent in regard to fatigue and to problems with consciousness, he said.
"In this open-label, randomized study, patients treated with IDDS plus comprehensive medical management had about 2.5 months more good-quality life at the end of life than similar patients on comprehensive medical management alone," said Dr. Smith, chairman of the Division of Hematology/Oncology, Medical College of Virginia Hospitals, Richmond.
This trial included 99 patients randomized to comprehensive medical management (CMM) and 101 patients randomized to CMM plus IDDS. About 60% of patients in each group had mixed neuropathic and nociceptive pain. Baseline morphine oral equivalent doses were 280 mg/d in the CMM group and 260 mg/d in the IDDS group.
Baseline visual analog scale (VAS) score was 7.59 in the CMM group and 7.44 in the IDDS group. The trial included patients with lung, breast, prostate, colon, and pancreatic cancers. Crossover was allowed for VAS pain scores greater than 5 and for side effects. Patients were assessed at baseline, 2, 4, 6, 8, 10, and 12 weeks, then monthly for 6 months. Intrathecal therapy was delivered with the Medtronic SynchroMed EL Infusion System.
The study was powered to detect a greater than 20% improvement in VAS pain score and/or in National Cancer Institute (NCI) Common Toxicity Criteria score. Clinical success was defined as either a 20% improvement in VAS pain score with equal or reduced toxicity, or a 20% improvement in toxicity with equal or reduced VAS pain score.
Dr. Smith reported that clinical success was achieved in 84.5% of IDDS patients vs 70.8% of CMM patients (P = .05). VAS pain scores improved by 52% in IDDS patients vs 39% in CMM patients (P = .055).
Toxicity attributable to opioids (see Figure 1) improved by 50% in IDDS patients vs 17% in CMM patients (P = .004). All measured toxicities but urticaria and impotence had larger reductions in the IDDS arm than in the CMM arm. Fatigue and reduced consciousness were significantly better on the IDDS arm (P < .05). Pruritus and impotence worsened on the CMM arm, Dr. Smith said.
"This open-label trial was not designed to measure survival as a planned endpoint, but the Kaplan-Meier survival curve of the groups as randomized suggests that IDDS might also improve survival [see Figure 2]. This makes intuitive sense, since IDDS was associated with reduced pain and its associated stress and with reduced drug toxicity," Dr. Smith said.
He pointed out that the 2 months of good quality of life associated with IDDS in these patients is more than the survival benefit associated with gemcitabine (Gemzar) in pancreatic cancer.
"This study shows that there are other ways of relieving pain than just escalating narcotic doses. IDDS is targeted pain therapy because it puts the drugs right where the nerve impulses go," Dr. Smith said. He added that "this invasive use of an implantable device is not for all cancer patients, only for those with refractory cancer pain."
The results of this trial were reported in detail in the October 2002 issue of the Journal of Clinical Oncology (20:4040-4049, 2002).