Methadone rotation for cancer pain: an observational study.

CONTEXT: Methadone is a useful option in the treatment of cancer pain. Despite its advantages, methadone use is complicated due to high interindividual variability in pharmacokinetics. Various rotation methods from other opioids have been proposed in mostly Caucasian populations. OBJECTIVES: This study aims to describe our experience with opioid rotation to methadone for management of cancer pain in a predominantly Asian population. METHODS: A retrospective review of 52 inpatients initiated on methadone for cancer pain from June 2015 to June 2018 was conducted. Our institution protocol for methadone rotation involves either one of two methods ('Stop-and-go' or the Edmonton 3-day rotation) based on the morphine-equivalent daily dose (MEDD), using an equianalgesic ratio of 10:1 for MEDD <1000 mg. To account for incomplete cross-tolerance, we further reduce the calculated dose by 30%. RESULTS: The majority of patients had mixed nociceptive-neuropathic pain (83%) and the predominant reason for methadone rotation was ineffective analgesia with other opioids (75%). The median MEDD before rotation was 104 mg. Effective analgesia (defined as a decrease in numerical rating scale (NRS) of ≥1 or attainment of NRS ≤3) was achieved within 3 days after rotation in 89% of patients. Patients with an MEDD ≤100 mg/day required a greater degree of uptitration of methadone dose after rotation compared with those with an MEDD >100 mg/day. CONCLUSION: Rotation to methadone according to our protocol is effective in achieving adequate analgesia in most patients experiencing nociceptive-neuropathic pain. Our results also suggest that a fixed equianalgesic ratio of 10:1 may be adequate for patients at low-to-moderate MEDD <400 mg/day.

PROgnostic Model for Advanced Cancer (PRO-MAC).

OBJECTIVE: To develop and validate a simple prognostic tool for early prediction of survival of patients with advanced cancer in a tertiary care setting. DESIGN: Prospective cohort study with 2 years' follow-up. SETTING: Single tertiary teaching hospital in Singapore. PARTICIPANTS: The study includes consecutive patients diagnosed with advanced cancer who were referred to a palliative care unit between 2013 and 2015 (N=840). Data were randomly split into training (n=560) and validation (n=280) sets. RESULTS: 743 (88.5%) patients died with a mean follow-up of 97.0 days (SD 174.0). Cox regression modelling was used to build a prognostic model, cross-validating with six randomly split dataset pairs. Predictor variables for the model included functional status (Palliative Performance Scale, PPS V.2), symptoms (Edmonton Symptom Assessment System, ESASr), clinical assessment (eg, the number of organ systems with metastasis, serum albumin and total white cell count level) and patient demographics. The area under the receiver operating characteristic curve using the final averaged prognostic model was between 0.69 and 0.75. Our model classified patients into three prognostic groups, with a median survival of 79.0 days (IQR 175.0) for the low-risk group (0-1.5 points), 42.0 days (IQR 75.0) for the medium-risk group (2.0-5.5 points), and 15.0 days (IQR 28.0) for the high-risk group (6.0-10.5 points). CONCLUSIONS: PROgnostic Model for Advanced Cancer (PRO-MAC) takes into account patient and disease-related factors and identify high-risk patients with 90-day mortality. PPS V.2 and ESASr are important predictors. PRO-MAC will help physicians identify patients earlier for supportive care, facilitating multidisciplinary, shared decision-making.

A review of whole brain radiotherapy outcomes in a high epidermal growth factor receptor mutation rate population: Does QUARTZ apply in Asia?

AIM: Whole brain radiotherapy (WBRT) is commonly used to treat brain metastases (BM) from nonsmall cell lung cancer (NSCLC). Its utility is increasingly being questioned after a recent randomized trial (QUARTZ) showed that its omission did not significantly impact the survival or quality of life of their patients recruited from UK and Australian centers. We report the patient characteristics and survival outcomes of our local population in comparison with theirs. METHODS: Medical records of patients who received WBRT in two tertiary hospitals over 18 months were reviewed. Characteristics and survival outcomes of patient with NSCLC receiving WBRT for the first time were evaluated. Patients with prior excision of BM or stereotactic radiotherapy were excluded. Treatment details including radiotherapy dose and use of tyrosine kinase inhibitors (TKIs) were recorded. RESULTS: Between January 2015 and June 2016, 116 patients with NSCLC received WBRT for their BM. Their median age was 65 years (range, 36-85) and median follow-up duration was 110 days (range, 14-840). A total of 102 (88%) patients had their driver mutation tested of which 59 (58%) were epidermal growth factor receptor (EGFR) mutants. Factors predicting for better survival were female gender (P < .001), EGFR mutant receiving TKIs (P = .013), prescription other than 20 Gray in five fractions (P = .003), and presence of more than four BM (P = .001). CONCLUSION: Our patients appear to be considerably different from those recruited into the QUARTZ trial. Further prospective studies should be done to evaluate the value of WBRT in our population.