Why do only one in six medical oncologists refer patients with cancer pain to pain or palliative care specialists?

According to a 2010 survey, reasons include: “pain specialists are not available in my region”, “pain specialists do not want to see patients with cancer”, “appointments with pain specialists are hard to get”, “specialists are too likely to recommend procedures for pain”, and “pain specialists do not understand oncology”.1

Study after study has shown that patients with cancer do experience pain, which often remains undertreated despite established guidelines.1,2 The prevalence of pain in patients with cancer ranges from 30% to 40% in those with early-stage disease to as high as 70% to 90% in those with advanced disease.3

RELATED: Supportive Care

One of the most challenging types of pain to treat—and a significant unmet need—is chronic persistent pain, also called moderate-to-severe intractable pain. Such pain can result from the disease itself, from surgery, as a result of medications, or from a genetic predisposition to feel greater pain. When these patients are refractory to conventional pain management, intrathecal drug delivery may be an effective option for managing both neuropathic and nociceptive cancer pain.3

In fact, a consensus panel has advocated “for a much wider application of intrathecal therapy to provide meaningful analgesia for patients with cancer pain.”3

However, a search of ClinicalTrials.gov for relevant research using the key words “intrathecal”, “cancer”, and “pain” found only four studies in the United States that are currently recruiting patients. Two of these studies are testing new agents and two are testing a drug-delivery system.

  • Resiniferatoxin. At the recent 39th Annual Regional Anesthesia and Acute Pain Meeting in San Diego, CA, National Institutes of Health investigators presented phase 1/2 data from the first two dosing cohorts of resiniferatoxin in patients with advanced cancer and severe refractory pain. Six patients received either a 13- or 26-mcg injection of resiniferatoxin into the intrathecal space. All patients showed a clinically meaningful improvement in quality of life, an average 20% reduction in pain intensity score at 2 weeks, and increased activity level. Two patients who were bed- or wheelchair-bound because of pain were able to walk soon after the injection. Resiniferatoxin selectively binds to the TRPV-1 receptor, inducing calcium influx-induced apoptosis of TRPV-1 nerve cells, resulting in a selective ablation. According to the drug’s manufacturer, Sorrento Therapeutics, Inc., based in San Diego, CA, a single intraspinal injection permanently blocks pain signal transmission without affecting normal sensation, motor control, or impairment of mental or physical faculties (www.clinicaltrials.gov [NCT00804154]).
  • Substance P-saporin (SP-SAP). The University of Texas Southwestern Medical Center, Dallas, is conducting a phase 1 study of SP-SAP in patients with histologically confirmed advanced cancer who are terminally ill and have intractable pain unrelieved by opioids. Each subject will be treated with a single dose via a percutaneous intraspinal catheter. The primary outcome measures are based on achieving a 20% reduction in chronic pain or opioid dose within 8 weeks of treatment on at least two of seven parameters (www.clinicaltrials.gov [NCT02036281]). SP-SAP is a chemical conjugate of substance P and a recombinant version of saporin that acts as a targeted neurotoxin.4
  • Infusion System, LLC Implantable Drug Delivery System (IDDS). The Alfred E. Mann Foundation for Scientific Research, in Valencia, CA, is enrolling patients with chronic pain responsive to intrathecal opioid analgesia, as demonstrated in a morphine trial, or patients with a previous successful intrathecal opioid therapy with an implantable pump, to undergo implantation of the IDDS for intrathecal delivery of morphine sulfate for pain control (www.clinicaltrials.gov [NCT01185470]).
  • Prometra Programmable Intrathecal Infusion Pump. Flowonix Medical, based in Mt. Olive, NJ, is prospectively evaluating the long-term safety of the Prometra system in a postapproval study. One of the two arms is enrolling new patients who are having a pump implanted; the other is continuing to follow patients who were part of the study prior to Food and Drug Administration approval of the pump. Primary outcome measure is rate of granuloma formation, with the hypothesis that the 5-year rate will be noninferior to that of the literature (www.clinicaltrials.gov [NCT01854229]).

Barriers to pain management reported by medical oncologists in the survey were poor pain assessment, patient reluctance to report pain, and patient reluctance to take analgesics as well as their own reluctance to prescribe opioids and perceived excessive regulation.1 One of the most startling findings is that these results mirror a similar survey conducted over two decades ago.5

References

  1. Breuer B, Fleishman SB, Cruciani RA, Portenoy RK. Medical Oncologists’ attitudes and practice in cancer pain management: a national survey. J Clin Oncol. 2011;29(36):4769-4755.
  2. Fisch MJ, Lee JW, Weiss M, et al. Prospective, observational study of pain and analgesic prescribing in medical oncology outpatients with breast, colorectal, lung, or prostate cancer. J Clin Oncol. 2012;30(16):1980-1988.
  3. Deer TR, Smith HS, Burton AW, et al. Comprehensive consensus based guidelines on intrathecal drug delivery systems in the treatment of pain caused by cancer pain. Pain Physician. 2011;14(3):E283-E312.
  4. Brown DC, Agnello K. Intrathecal substance P-saporin in the dog: efficacy in bone cancer pain. Anesthesiology. 2013;119(5):1178-1185.
  5. Von Roenn JH, Cleeland CS, Gonin R, et al. Physician attitudes and practice in cancer pain management: a survey from the Eastern Cooperative Oncology Group. Ann Intern Med. 1993;119(2):121-126.