PEP Topic 
Refractory/Intractable Pain

KRN 5500 is a spicamycin derivative that has appeared to reduce nerve-injury-induced neuropathic pain in animal models. This substance was examined for its effect on pain in patients with cancer who had refractory neuropathic pain.

Effectiveness Not Established

Research Evidence Summaries

Weinstein, S.M., Abernethy, A.P., Spruill, S.E., Pike, I.M., Kelly, A.T., & Jett, L.G. (2012). A spicamycin derivative (KRN5500) provides neuropathic pain relief in patients with advanced cancer: A placebo-controlled, proof-of-concept trial. Journal of Pain and Symptom Management, 43, 679–693.

doi: 10.1016/j.jpainsymman.2011.05.003

Study Purpose:

To evaluate the safety and efficacy of KRN5500 for refractory neuropathic pain in patients with advanced cancer

Intervention Characteristics/Basic Study Process:

KRN5500 is an agent that inhibits certain enzymes that may modulate aspects of neuropathic pain. Patients were randomly assigned to receive up to 8 weekly doses of the study drug or placebo. Patients were followed over 14 weeks. Patients were allowed to continue their usual pain treatments. KRN5500 was given in escalating IV doses ranging from 0.6–2.2 mg/m2. Study assessments were done at baseline, during weekly clinic visits, and at the end of 14 weeks.

Sample Characteristics:

  • The study reported on 19 patients with a mean age of 61.7 years (SD = 12.7 years).
  • The sample was 52.6% male and 47.4% female.
  • Cancer types were not described. The majority of patients had chemotherapy-induced peripheral neuropathy, and most had symptoms in the lower extremities.  
  • All patients had mean pain ratings of 6.4 or more on an 11-point numeric rating scale at study entry.


This was a multisite, outpatient study conducted in the United States and Puerto Rico.

Phase of Care and Clinical Applications:

  • Patients were in the late effects and survivorship phase of care.
  • The study has clinical applicability for elder care.

Study Design:

This was a double-blind, randomized, placebo-controlled, dose-finding trial.

Measurement Instruments/Methods:

  • Numeric pain scores and pain medications used were documented daily in patient diaries.
  • Adverse events (AEs) were defined according to U.S. Food and Drug Administration guidelines.
  • Neuropathic pain was documented.
  • Patients completed the 12-item Short Form Health Survey (SF-12).


  • The mean number of days of treatment with KRN5500 was 40, and the median total dose was 1.27 mg/m2 per week. 
  • All of the patients on the study drug experienced at least one treatment-related AE compared to 86% of those receiving placebo. The most frequent AE was nausea and vomiting. No serious AEs were assessed as related to the study drug.   
  • Those on KRN5500 had a 24% median decrease in pain rating scores from baseline, compared to those on placebo, who had a 0% change (p = 0.03). 
  • No significant differences were found between groups in daily pain ratings from patient diaries.  Other study assessments showed mixed results.


This study provided some initial information regarding safety and efficacy of KRN5500 in a small cohort of patients.


The sample size was small, with fewer than 30 patients.

Nursing Implications:

 No conclusions can be drawn regarding the overall safety and efficacy of this drug. Further research in this area is needed.