Effectiveness Not Established

Extended and Sustained Release Opioids

for Peripheral Neuropathy

Sustained-release and extended-release opioids, which make use of time-release formulation, take effect within a specific time. Sustained-release drugs remain in the bloodstream in a stable amount for a longer time than do immediate-release opioids. As a result, patients do not have to take sustained-release medications as often as immediate-release drugs. Sustained-release opioids have been evaluated in the context of chronic cancer-related pain, peripheral neuropathy, and for the relief of dyspnea.

Research Evidence Summaries

Nagashima, M., Ooshiro, M., Moriyama, A., Sugishita, Y., Kadoya, K., Sato, A., . . . Katoh, R. (2014). Efficacy and tolerability of controlled-release oxycodone for oxaliplatin-induced peripheral neuropathy and the extension of FOLFOX therapy in advanced colorectal cancer patients. Supportive Care in Cancer, 22, 1579–1584.

Study Purpose

To investigate the efficacy and tolerability of oxycodone for oxaliplatin-induced peripheral neuropathy (OIPN) with FOLOFOX therapy in patients with colorectal cancer (CRC)

Intervention Characteristics/Basic Study Process

This was a single-center retrospective study of 64 patients with CRC receiving FOLFOX therapy. Controlled-release (CR) oxycodone was concomitantly administered to 29 patients (OXY group). An additional 35 patients (non-OXY group) were not given oxycodone during FOLFOX therapy. The incidence and severity of OIPN and the number of FOLFOX treatments were measured and compared.

Sample Characteristics

  • N = 64  
  • MEAN AGE = 64.9 years (non-OXY); 62.7 years (OXY)
  • MALES: 54.2% (non-OXY); 55.2% (OXY), FEMALES: 48.6% (non-OXY); 44.8% (OXY)
  • KEY DISEASE CHARACTERISTICS: Advanced-stage disease (III or IV); all received a gross dissection of primary CRC and subsequently received curative-intent FOLFOX therapy; all were greater than 18 years of age; World Health Organization performance status of 0 or 1; life expectancy greater than six months; none could have preexisting peripheral neuropathy or exposure to previous neurotoxic chemotherapeutic agents
  • OTHER KEY SAMPLE CHARACTERISTICS: All patients received standard FOLFOX therapy (bolus of 85 mg/m2 oxaliplatin, leucovorin, and 400 mg/m2 5-FU followed by a 48-hour continuous infusion of 5-FU at 2,500 mg/m2 given every two weeks). Bevacizumab, cetuximab, or panitumumab was administered prior to mFOLFOX6 in 27 cases. FOLFOX was continued until disease progression, a decision to use alternative therapies was made, unacceptable toxicities occurred, or a patient refused additional treatment.

Setting

  • SITE: Single-site    
  • SETTING TYPE: Outpatient    
  • LOCATION: Toho University Sakura Medical Center in Sakura, Japan

Phase of Care and Clinical Applications

  • PHASE OF CARE: Active antitumor treatment
  • APPLICATIONS: Elder care, palliative care 

Study Design

Patients in the OXY and non-OXY groups were evaluated for neurotoxicity. Severity of pain, sensory status, and motor dysfunction were evaluated.

Measurement Instruments/Methods

The National Cancer Institute's (NCI's) Common Terminology Criteria for Adverse Events (CTCAE) was used to evaluated neurologic toxicity. A peripheral sensory neuropathy subscale was used to grade clinical severity. Grade 1 could be asymptomatic or could include a loss of deep tendon reflex or paresthesia (including tingling) that did not interfere with function; grade 2 included sensory alterations or paresthesia (including tingling) that interfered with function but not with activities of daily living (ADL); and grade 3 included sensory alterations or paresthesia that interfered with ADL. Pain intensity was measured on a numeric scale after each cycle of FOLFOX therapy.

Results

All patients in the OXY group and 33 out of 35 patients in the non-OXY group experienced grades 1 or 2 sensory neuropathy. Grade 3 neurotoxicity was not observed in the OXY group whereas two patients (5.7%) in the non-OXY group reported grade 3 sensory neuropathy. In the OXY group, sensory neuropathy grades improved in all patients. CR oxycodone was discontinued in 10 patients (34.5%) in the OXY group after completions of FOLFOX therapy. No discontinuations because of OIPN occurred in the OXY group, and 10 discontinuations occurred in the non-OXY group. Patients in the OXY group received a median of 13 cycles. Those in non-OXY group received a median of seven cycles. The median total oxaliplatin dose was higher in OXY group than the non-OXY group (1072.3 mg/m2 versus 483 mg/m2, respectively).

Conclusions

CR oxycodone may attenuate OIPN and extend FOLFOX therapy in patients with CRC.

Limitations

  • Small sample (< 100)
  • Risk of bias (no control group)
  • Risk of bias (no blinding)
  • Risk of bias (no random assignment)
  • Risk of bias (no appropriate attentional control condition)
  • Selective outcomes reporting
  • Measurement validity/reliability questionable
  • Design observations and retrospective: Pain intensity in 23 patients (79.3%) in the OXY group remained mild throughout the entire study period with no significant change. No quantitative data regarding pain severity were provided. The CTCAE is not a sensitive measure of neuropathy, and it was completed by the provider rather than the patient. Neuropathy symptoms may have been masked by oxycodone.

Nursing Implications

Additional research on oxycodone and other opioid use for OIPN is needed. This study suggests changes caused by oxycodone, but it has several limitations.

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