Potentially inappropriate medication use in older people with cancer: prevalence and correlates.

OBJECTIVES: Potentially inappropriate medication (PIM) use has been associated with an increase in adverse drug events, hospitalization and mortality. This study investigated the prevalence and factors associated with PIM use in patients presenting to a medical oncology outpatient clinic. MATERIALS AND METHODS: Consecutive patients (n=385) aged ≥ 70 years referred to a medical oncology outpatient clinic between January 2009 and July 2010 completed a structured data collection instrument. The instrument assessed medication use, diagnoses, self-reported falls in the previous six months, pain (10-point visual analog scale [VAS]) and distress (10-point VAS). Frailty was defined using exhaustion, weight loss, Karnofsky Performance Scale, instrumental activities of daily living and physical function. PIM use was defined by the Beers Criteria. Logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with PIM use. RESULTS: In total, 26.5% (n=102) of the sample used ≥1 PIM. The five most prevalent classes of PIMs were benzodiazepines (n=34, 8.8%), tricyclic antidepressants (n=16, 4.2%), alpha-adrenoreceptor antagonists (prazosin) (n=15, 3.9%), propulsives (metoclopramide) (n=15, 3.9%) and non-steroidal anti-inflammatory drugs (n=14, 3.6%). In multivariate analyses, PIM use was associated with age 75-79 years (OR 1.83; 95%CI 1.02-3.26) compared to age 70-74 years, using ≥ 5 medications (OR 4.10; 95%CI 2.26-7.44) compared to <5 medications and being frail (OR 3.05; 95%CI 1.18-7.87) compared to being robust. CONCLUSION: More than one quarter of older people with cancer used one or more PIMs, and this was associated with being frail compared to being robust.

Systematic review of oral cryotherapy for management of oral mucositis caused by cancer therapy.

PURPOSE: This systematic review analyzed the strength of the literature and defined clinical practice guidelines for the use of oral cryotherapy for the prevention and/or treatment of oral mucositis caused by cancer therapy. METHODS: A systematic review on relevant oral cryotherapy studies indexed prior to 31 December 2010 was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO) using OVID/MEDLINE, with publications selected for review based on defined inclusion and exclusion criteria. Findings from the reviewed studies were integrated into guidelines based on the overall level of evidence for each intervention. Guidelines were classified into three types: recommendation, suggestion, or no guideline possible. RESULTS: Twenty-two clinical studies and two meta-analyses were analyzed. Results were compared with the MASCC/ISOO guidelines published in 2007. The recommendation for the use of oral cryotherapy to prevent oral mucositis in patients receiving bolus fluorouracil (5-FU) was maintained, in agreement with the 2007 guidelines. A suggestion for use of oral cryotherapy to prevent oral mucositis in patients receiving high-dose melphalan as conditioning regimen with or without total body irradiation for HCST was revised from the 2007 guidelines. No guideline was possible for any other intervention, due to insufficient evidence. CONCLUSIONS: The evidence continues to support the use of oral cryotherapy for prevention of oral mucositis in patients receiving bolus 5-FU chemotherapy or high-dose melphalan. This intervention is consistent with the MASCC/ISOO guidelines published in 2007. The literature is limited by the fact that utilization of a double-blind study design is not feasible. Future studies that compare efficacy of oral cryotherapy with other mucositis agents in patients receiving chemotherapy with relatively short plasma half-lives would be useful.

Comparing 3 methods of monitoring gentamicin concentrations in patients with febrile neutropenia.

Several nomograms and algorithms have been developed to individualize pharmacokinetic monitoring with their own advantages and disadvantages. This study compared 3 pharmacokinetic methods for predicting doses and monitoring of gentamicin in adult patients with febrile neutropenia. A retrospective study of 75 patients with febrile neutropenia was conducted at the Royal Adelaide Hospital, South Australia. Each patient received a course of once-daily gentamicin and had 2 sets of paired gentamicin serum concentrations. Pharmacokinetic parameters and ensuing doses were compared using 3 pharmacokinetic methods: (1) sequential Bayesian algorithm for gentamicin (SeBA-GEN), (2) Sawchuk-Zaske, and (3) Therapeutic Guidelines: Antibiotic Dose Adjustment Nomogram. The initial median (range) dose of gentamicin administered was 400 (240-640) mg. SeBA-GEN and Sawchuk-Zaske methods recommended similar subsequent gentamicin dose adjustments of 400 (280-640) mg and 400 (280-640) mg, respectively, whereas the Therapeutic Guidelines recommended an increase to 1390 (210-6240) mg. For the Therapeutic Guidelines, 64% of the patients had measured serum gentamicin concentrations that were below the minimum line of the nomogram for the first set of concentrations with only 32% of these patients having an area under the curve value of <70 mg h/L as calculated by SeBA-GEN. The SeBA-GEN method showed a statistically significant increase (68%-77%) in patients attaining the target concentrations of maximum concentration (Cmax) 15-25 mg/L compared with the Sawchuk-Zaske method (72%-65%, P > 0.05). SeBA-GEN also demonstrated greater precision in predicting the area under the curve, Cmax, and minimum concentration (Cmin) compared with the Sawchuk-Zaske method. In conclusion, as the Bayesian approach, that is, SeBA-GEN demonstrated greater precision and more patients were attaining the target concentrations, it is therefore the preferred method for gentamicin monitoring in patients with febrile neutropenia.

Polypharmacy in elderly patients with cancer: clinical implications and management.

More and more elderly people with cancer are treated in oncology clinics worldwide every year, many of whom have comorbid disorders treated with one or more drugs. Moreover, these patients might also take self-prescribed over-the-counter drugs or complementary and alternative medicines, which they might not tell their doctor about. Initiation of chemotherapy with one or more cytotoxic or targeted agents and drugs for treatment of cancer symptoms or toxic effects related to treatment can result in polypharmacy. We examine the clinical implications of polypharmacy. Challenges for the medical teams who treat elderly patients with cancer include identification of what drugs are actually being taken by the patient, avoidance or management of any adverse effects or drug interactions, and reassessing the patient's overall treatment. We address these issues and propose practical recommendations for management of treatment for elderly patients with cancer.

Subcutaneous fentanyl and sufentanil infusion substitution for morphine intolerance in cancer pain management.

Eleven patients with cancer pain in a palliative care and chronic pain service required cessation of morphine due to unacceptable opioid side effects. In this retrospective study fentanyl was evaluated as a second-line subcutaneously infused opioid. Starting doses ranged from 100 to 1000 micrograms/24 h, and the duration of fentanyl infusion was 3-70 days. The clinically derived mean relative potency of fentanyl to morphine infusions was 68:1 (SD +/- 23; range: 15-100), and we now recommend cautious dose conversion at an approximate equivalence of 150-200 micrograms fentanyl for 10 mg morphine in non-opioid naive chronic cancer pain patients. All patients demonstrated an improvement in the adverse effect(s) for which the change in opioid was undertaken. Adequate pain relief was achieved in all but 1 patient with mixed nociceptive and neuropathic pelvic pain for whom an epidural infusion of a local anaesthetic/opioid mixture was required. Fentanyl was changed to the more potent synthetic opioid sufentanil in 2 patients for whom the fentanyl dose necessitated too large a volume for the portable syringe driver in use. The clinically derived sufentanil to fentanyl relative potencies were 24:1 and 16:1, respectively. This achieved good analgesia and maintained the favourable side-effect profile seen with fentanyl. Subcutaneous infusion appears to be a safe and viable route of fentanyl delivery, and provided effective analgesia with a low incidence of adverse effects in this small selected group of patients who were intolerant of subcutaneous morphine. We suggest a trial of subcutaneous fentanyl for selected patients who have intractable adverse effects on morphine, and it is now the second-line infusable opioid in our service. Further prospective evaluation of the role of these two synthetic mu opioid agonists in palliative care practice is warranted, as part of an evolving picture of variation in opioid side-effect profile seen with different drugs within the class.