ASCO Guidelines Provide Road Map for Cancer Pain Management With Opioids

Pain management is a core component of cancer care. However, use of agents to curb these effects, especially opioids present challenges in practice including stigma around opioid abuse, reimbursement issues, lack of availability, and patient fear of addiction. The American Society of Clinical Oncology (ASCO) has updated its guidelines providing recommendations for the management of cancer pain with opioids.¹

Approximately 55% of patients experience pain during active cancer treatment and more than 66% of patients with advanced disease will experience cancer-related pain. Although guidelines for managing cancer-related pain exist, there are few guidelines focused on exclusively on opioids. Opioids approved by the FDA are viable options for pain relief and use should be determined based on several factors including cost, half-life, pharmacokinetic properties, and route of administration. If a clinician is unsure of the best agent palliative care or pain specialists should be consulted.¹

A multidisciplinary expert panel consisting of patient representatives and an ASCO guidelines staff member with health research methodology expertise developed the guidelines that were informed by evidence including 16 randomized controlled trials and 31 systemic reviews from January 1, 2010, to February 17, 2022.¹

The supportive care guidelines addressed 7 key questions for patients with cancer pain under all of which fell under the umbrella of the leading question: “In what circumstances should opioids be used to manage cancer pain in adults, how should opioids be administered, and how should opioid adverse effects be prevented or managed?”¹

Regarding the circumstances under which opioids should be offered, an evidence-based strong recommendation was given by the panel that all patients with moderate-to-severe pain related to cancer or active treatments should be offered, unless otherwise determined, opioids to be given as needed as the benefits outweigh the harm. According to informal consensus, opioids should be administered at the lowest possible dose, early assessment and titration should occur as well; however, there is insufficient evidence to recommend a single set of ranges for escalation. The authors wrote, “In general, the minimum dose increase is 25% [to] 50%, but patient factors such as frailty, comorbidities, and organ function must be evaluated and considered when changing doses.”¹

In terms of opioid-induced adverse event (AE) management, the panel noted several events with recommendations for prevention and treatment. These events included constipation, delirium and neurotoxicity, endocrinopathy, nausea and vomiting, pruritus, sedation and respiratory depression, and urinary retention. Guidelines for opioid-induced constipation have been published and should be referenced.² All others should be treated based on clinical experience.¹

The guidelines advised that patients with renal or hepatic impairment should receive more frequent dose adjustments and clinical observations. Patients with renal impairment who are currently undergoing treatment with an opioid may rotate to methadone as it is excreted fecally. For those who are given opioids that are primarily eliminated in urine, such as fentanyl, oxycodone, and hydromorphone, careful titration, and frequent risk monitoring for accumulation of the parent drug or active metabolites should occur. Both recommendations are supported by strong informal consensus.

Additional recommendations stated that patients who have been taking other analgesics such as nonsteroidal anti-inflammatory drugs, may continue taking them after initiating opioid use if they provide further pain relief. However, there is insufficient evidence on a set range for dose escalation and whether genetic testing should be performed to guide administration of opioids.

The panel noted that there is insufficient evidence to provide a recommendation for a specific short-acting opioid for breakthrough pain, but patients receiving opioids around the clock should be given immediate release agents at a dose of 5% to 20% of the daily regular morphine equivalent daily dose for breakthrough pain. As with the titration recommendation, there is insufficient evidence to support a specific opioid for breakthrough pain.

A strong evidence-based recommendation for opioid rotation is included in the guideline. Specifically, the evidence supports switching agents when AEs are poorly managed, there are logistical or cost concerns, trouble with the route of administration or absorption of an opioid, or patients have pain that is refractory to dose titration. As with the titration recommendation, there is insufficient evidence to support a specific opioid for breakthrough pain.

The guidelines also stated that because patients with multiple chronic conditions represent a diverse and complex population shared decision making is crucial and clinicians should review all chronic conditions present when determining a treatment plan. It was noted that patients with persistent noncancer pain who were already being treated with opioids and later developed cancer, may have a challenging time obtaining pain relief.

Prior to prescribing opioids, physicians, patients, and caregivers should discuss expectations, goals, pain, and concerns about the treatment; education as well as regular follow-up is key between clinicians and patients. Shared decision-making should also take cost into account and patients should be informed of financial counseling services. To prevent or manage AEs to opioid use, education, and strategies of prevention to known effects should be given by clinicians.¹

As there are few guidelines focused solely on opioids for pain management, evidence for several of the questions was limited leading the panel to reply on consensus or they could not make a recommendation; however, the panel noted that the use of opioids for cancer pain management has been routine. The panel recommended that to determine the best approach of pain management for patients with a substance use disorder, clinicians should discuss with a palliative care, pain, and/or substance abuse disorder specialist.¹

A draft of the recommendations was made available to the public for comment from July 8, 2022, through July 22, 2022, and for each recommendation, 88% to 100% of respondents agreed or agreed with slight modifications. Additionally, ASCO noted that most randomized controlled trials included in the analysis had an intermediate or high risk of bias and further questions remain about the use of opioids for cancer pain management.¹

References

1. Paice JA, Bohlke K, Barton D, et al. Use of opioids for adults with pain from cancer or cancer treatment: ASCO guideline. J Clin Oncol. Published online December 5, 2022. doi:10.1200/JCO.22.02198
2. Larkin PJ, Cherny NI, La Carpia D, et al; ESMO Guidelines Committee. Diagnosis, assessment and management of constipation in advanced cancer: ESMO clinical practice guidelines. Ann Oncol. 2018;29(suppl 4):iv111-iv125. doi:10.1093/annonc/mdy148