An issue sometimes more difficult to treat than the underlying disease: opioid abuse in cancer survivors. Some thoughts and a case report from an oncologist.
Terminal sick patients are an important indication group for the use of potent opioids. But what about the ever-increasing number of patients who survive their illness? Many of them subsequently struggle with substance dependency. Often we cannot know which patients will survive. We see acute pain and suffering of the patient and want to do something about it. In addition, we are limited by the potential negative effects of other painkillers available. We may have learned to avoid non-opioid analgesics in chemotherapy patients, for example, because NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) could mask a fever, which can sometimes be the only sign of a life-threatening infection. NSAIDs also have complex effects on bleeding and coagulation risks. Paracetamol can affect the liver and NSAIDs the kidneys, and since many chemotherapies can irreversibly damage these organs, we do not want to burden them additionally (Source 1).
These limitations drive many practitioners into a corner from which all pain is treated with opioids. There is no evidence for this procedure. Once we were taught that pain is "the fifth vital sign" and that a good doctor aggressively approaches this pain. There was also a widespread opinion that patients with real pain could not become addicted. This is misdirected at best and wrong at worst. Like all other pain patients, cancer patients can slip into substance abuse.
Prof. Dr. Alison Wakoff Loren of Pennsylvania University Hospital, Department of Hematology and Oncology, describes in an article in the New England Journal of Medicine (Source 1) the case of a 24-year-old Chronic Myeloid Leukemia (CML) patient who developed acute graft-versus-host disease (GVHD) of the gastrointestinal tract as well as chronic GVHD in the skin, connective tissue and joints after allogeneic stem cell transplantation. Due to severe pain, the patient first received morphine and oxycodone and finally hydromorphone. In addition, referrals to psychiatrists and pain therapy were made to assist in the treatment of the increasingly complex pain syndrome and the depressed mood.
During the weekly performances, the patient complained of drowsiness, pruritus and constipation and her partner expressed concerns about her use of hydromorphone. The patient finally admitted to having her internist prescribe her hydromorphone and to taking it every one to two hours.
They made a mutual agreement that the partner would keep the hydromorphone under lock and key and give it to the patient in adequate doses and intervals, that she would present herself regularly to the psychiatrist and would not obtain prescriptions from other doctors (whose hematologist reassured herself from the internist).
But the problems continued to simmer. Although the pain could be alleviated by immunosuppression, the patient insisted that lower opioid doses were not sufficient. She manipulated the treatment team, was late for appointments, avoided the pain therapy specialists and redeemed old benzodiazepine prescriptions (in the USA once prescribed drugs can be "prolonged" or used several times in pharmacies under certain conditions without a follow-up prescription). The patient finally admitted the substance abuse and agreed to treatment.
But it was virtually impossible to find an in-patient rehabilitation place that was affordable or would be covered by insurance. When the doctor finally found an institution that accepted her insurance, the center rejected the patient because of her medical history - "we can't treat her here, the patient is too complicated" it was said.
While the doctor and her partner were looking for an outpatient therapy place, the patient had to go to the hospital due to bacteremia. The bacteria, Pseudomonas Oryzihabitans, which occurs primarily in tap water, led the doctor to suspect that the patient crushed and dissolved hydromorphone tablets in order to inject them into her central catheter, which was immediately removed.
According to her partner, the patient could hardly stay awake even after that and he found hiding places with hydromorphone everywhere in the house. She refused to consult a specialist for alternatives such as methadone therapy. On the advice of the pain doctors, the hematologist provided a final dose of opioid to compensate for the pain.
In the following month, the patient was again hospitalized elsewhere, febrile with skin abscesses. She claimed that they came from scratches by the dog, but the doctor was concerned that it could be skin popping - a common practice among addicts when vein conditions are poor, as in this patient. She informed the doctors of the other hospital about the history and warned them to closely monitor her intravenous access.
A few days later, the patient was found dead in her hospital bed. Her leukemia was in remission. "The possibility that the patient might have overdosed herself does not let me go," the hematologist concludes in the report.
In the USA alone, more than 70,000 people died of drug overdoses in 2017. With the exception of lung cancer, no tumor type alone causes such numbers. More than half of these deaths (47,600) were related to opioids (Source 2). More than 17,000 of these were related to medically prescribed opioids. Compared to 1999, this represents a five-fold increase (3,442).
"We first treat the pain and then think about the consequences later." sums up Prof. Loren. She thinks that the responsibility for this dilemma lies with us. Many oncologists use opioids generously as if there were no tomorrow - but for more and more patients there is a tomorrow. Many of them continue to live with chronic health problems that are consequences of tumor therapy, but opioid dependence should not be one of them.
The situation in Germany is not necessarily comparable to that in the USA. But the hematologist conclusion is universally relevant. Oncologists are used to dealing with opioids, but must also be able to take them away and sometimes administer them in limited doses or not at all. Risks, prevention and solution possibilities for opioid abuse must be very present for the therapist in charge. In the present case, a strict and accurate pre-transplantation screening did not reveal any risk factors (except for the young age). However, between transplantation and the developments described above, some clues emerged: Depression, resumption of smoking, functional limitations.
Research to expand our non-opioid analgesics options in cancer patients could contribute to more low-risk choices in the treatment of chronic pain.
Finally, a very insightful TEDx lecture by a physician on the opioid crisis is recommended to the interested reader.
Sources:
1. Loren, A. W. Harder to Treat Than Leukemia - Opioid Use Disorder in Survivors of Cancer. New England Journal of Medicine 379, 2485-2487 (2018).
2. National Institute on Drug Abuse. Overdose Death Rates. (2019). Available at: https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates. (Accessed: 10th February 2019)