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3 days ago

Cholangiocarcinomas (CCAs) are a group of rare and often difficult-to-diagnose cancers that arise from epithelial cells of bile ducts. While the standard first-line treatment for locally advanced or metastatic CCAs is chemotherapy, targeted therapy developed in recent years has expanded the armamentarium of second-line treatment options for patients failing first-line chemotherapy. This article summarizes key challenges in the management of CCAs and the promising data from the FIGHT-202 trial (Fibroblast Growth Factor Receptor Inhibitor in Oncology and Hematology Trial), which investigated the safety and antitumour activity of pemigatinib in patients with previously treated intrahepatic CCA (iCCA) with fibroblast growth factor receptor (FGFR) 2 gene alterations.  

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Sustained-release oxycodone addresses challenges of cancer pain management in the elderly

05 Aug 2020
With ageing populations, many countries face increasing healthcare demands associated with the management of diseases and comorbidities common among the elderly, such as cancer, osteoarthritis and rheumatoid arthritis, and the pain associated with these conditions. In recent years, there has been growing evidence supporting the use of sustained-release (SR) oxycodone (OxyContin®, Mundipharma) as a pain management option for elderly patients, particularly those experiencing chronic cancer-related pain. This article summarizes the key points and evidence from two seminal papers – a consensus statement of an international expert panel on opioids and the management of chronic severe pain in the elderly as well as a multicentre, open-label randomized controlled trial investigating the efficacy and safety of SR oxycodone in cancer pain treatment. 


Challenges of managing pain in the elderly

Pain is a common symptom among the elderly (aged 65 years). In the US, chronic pain affects up to 17.5 million elderly individuals, while in the UK, approximately 60 percent of elderly individuals report some daily pain or discomfort. Despite these figures, pain remains frequently under-reported, undertreated and poorly managed, while opioids are underprescribed to the elderly. [Pain Pract 2008;8:287-313; Drugs Aging 2005;22:641-654]

The consensus statement by Pergolizzi J, et al, lists change in the perception of pain among the elderly as one of the challenges in its management. “The increase in pain threshold could lead to delays in diagnosis and poor recovery, while the decreased tolerance to severe pain presents management problems,” wrote the authors. Another challenge is the effect that physiological decline in organ function has on drug pharmacology, namely, the onset of action, rate of elimination and half-life of drugs, the statement highlighted. [Pain Pract 2008;8:287-313]

Drug-drug interactions, renal dysfunction and immunosuppression: Key concerns with morphine

Polypharmacy increases the risk of drug interactions and adverse events (AEs; ie, dizziness and respiratory depression) in patients who are already at high risk of falls and fractures. On average, polypharmacy-associated adverse drug reactions cost the US healthcare system an excess of USD 1 million annually. [Pain Pract 2008;8:287-313]

“The average nursing home patient is taking seven prescription medicines and the average elderly person takes 2–4 prescription drugs per day,” noted the authors of the consensus statement. Thus, elderly patients face a high risk of potential drug-drug interactions and associated AEs. In particular, drug interactions with morphine need to be taken into account as the compound’s metabolism via liver enzymes may be affected by other drugs.

Renal dysfunction is common among elderly patients, which may increase the half-life of active drugs and metabolites. Morphine use in these patients can result in a heightened risk of intoxication due to the accumulation of inactive morphine-3-glucoronide and morphine-6-glucoronide metabolites. [Pain Pract 2008;8:287-313; Mayo Clin Proc 2009;84:613-624] In elderly patients with renal impairment, the authors of the consensus statement recommend that opioid doses be reduced, a longer time interval be used between doses, and creatinine clearance be monitored, also noting that oxycodone appears to be a safe choice for opioid treatment in such patients. [Pain Pract 2008;8:287-313]

Elderly patients are at a particularly high risk of suppressed immune responses, as the immune system becomes less active with age and elderly patients are more likely to be taking immunomodulating drugs. Several opioids are known immunosuppressors, with morphine being the most immunosuppressive. [J Neuroimmunol 1998;83:19-28; Pain Pract 2008;8:287-313] In comparison, oxycodone has been reported to be less immunosuppressive, highlighted the authors of the consensus statement. The consensus statement also noted that while the long-term clinical impact of opioid-induced immunomodulation is unclear and warrants further study, the possibility of pain control with a non-immunosuppressive therapy is an important factor to be considered in opioid use.

SR oxycodone: A viable strategy in noncompliance and dose titration

Cognitive impairment and memory loss – either due to pathology or medication – are common issues among the elderly, which, confounded by possible sight and hearing impairment, can lead to reduced compliance and affect AE reporting. Additionally, cognitive impairment and dementia often lead to atypical behaviour, including atypical reactions to pain. SR preparations, noted Pergolizzi J, et al, are preferred in patients who may have compliance problems, as dosing frequency can be reduced. [Pain Pract 2008;8:287-313]

While a dose-titration procedure with immediate-release (IR) morphine has been recommended to gauge the analgesic effect at the start of pain management, the 4-hourly scheduled procedure is inconvenient, results in poor compliance and increases patients’ risk of AEs. With this in mind, Pan H, et al, sought to investigate the effect of SR oxycodone as a background dose during the initial dose titration of morphine to achieve adequate pain relief in patients with moderate-to-severe cancer pain. [Medicine 2019;98:e15505]

The study enrolled 192 patients who required regular use of a strong opioid for managing chronic cancer-related pain. The patients were randomized in a 1:1 ratio to receive SR oxycodone 10 mg every 12 hours and IR morphine as needed, or IR morphine alone every 4 hours at an initial dose of 5 mg. A total of 185 patients were included in the analysis (SR oxycodone group, n=95; IR morphine group, n=90) after one patient in the SR oxycodone group and six patients in the IR morphine group dropped out of the study. The investigators found that SR oxycodone improved the efficiency of titration, with 94.7 percent of patients in the SR oxycodone group achieving adequate pain control within the first two cycles of titration (1.078 ± 0.269). In comparison, patients in the IR morphine group required 1–4 titration cycles to achieve adequate pain control (1.218 ± 0.550).

Importantly, SR oxycodone treatment was associated with a significantly increased response rate vs IR morphine during the first cycle of titration (87.4 percent vs 72.2 percent; p=0.010). (Figure)

“The findings of our study showed superior efficiency of SR oxycodone for dose adjustment in cancer pain management compared with IR morphine. The use of SR oxycodone spared the patients the multiple-dose schedule,” noted the investigators, adding that the use of SR oxycodone may reduce the need for opioid switching from IR morphine to a controlled-release preparation, thereby improving patient compliance.

The study also demonstrated that the use of SR oxycodone as a background medication significantly reduced the incidence of morphine-induced side effects. Ultimately, the promising results support the use of SR oxycodone as a background medication for dose titration in clinical management of chronic cancer pain. [Medicine 2019;98:e15505]

MUN-062_F

 


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Most Read Articles
3 days ago

Cholangiocarcinomas (CCAs) are a group of rare and often difficult-to-diagnose cancers that arise from epithelial cells of bile ducts. While the standard first-line treatment for locally advanced or metastatic CCAs is chemotherapy, targeted therapy developed in recent years has expanded the armamentarium of second-line treatment options for patients failing first-line chemotherapy. This article summarizes key challenges in the management of CCAs and the promising data from the FIGHT-202 trial (Fibroblast Growth Factor Receptor Inhibitor in Oncology and Hematology Trial), which investigated the safety and antitumour activity of pemigatinib in patients with previously treated intrahepatic CCA (iCCA) with fibroblast growth factor receptor (FGFR) 2 gene alterations.  

Dr. Tai-Chung Lam, 14 Feb 2020
While the armamentarium of therapies for metastatic non-small-cell lung cancer (NSCLC) has evolved to include various targeted therapies and immunotherapeutic agents, combinations with optimal efficacy and tolerability remain to be elucidated. At the 8th Joint Scientific Meeting of the Royal College of Radiologists (RCR) and Hong Kong College of Radiologists (HKCR) and 27th Annual Scientific Meeting of HKCR, Professor Tai-Chung Lam of the Department of Clinical Oncology, the University of Hong Kong, discussed the use of immunotherapy-based combinations for the management of EGFR-mutated NSCLC, with an emphasis on the role of the anti–PD-L1 antibody, atezolizumab. 
Dr. Joaquin Mateo, Prof. Henrik Grönberg, 3 days ago
The poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor olaparib was shown to prolong radiologic progression-free survival (rPFS) in men with metastatic castration-resistant prostate cancer (mCRPC) harbouring alterations in homologous recombination repair (HRR) genes in the PROfound study. These positive results were reinforced by the final overall survival (OS) analysis of PROfound, presented at the European Society for Medical Oncology Virtual Congress 2020 (ESMO 2020), which support the implementation of genomic testing for mCRPC in clinical practice.
Dr. Keith Wong, 3 days ago
The B-cell lymphoma-2 (BCL-2) inhibitor, venetoclax, has demonstrated promising efficacy in relapsed/refractory chronic lymphocytic leukaemia (CLL). However, the associated risk of tumour lysis syndrome (TLS) in certain patients necessitates prophylactic measures and close monitoring. In an interview with MIMS Oncology, Dr Keith Wong from the haematology department of a public hospital in Hong Kong discussed important treatment considerations for patients with CLL, and highlighted prophylactic and supportive measures established at his hospital to mitigate the risk of TLS complications associated with venetoclax-based therapy.