Does switching from oral to subcutaneous administration of methotrexate influence on patient reported gastro-intestinal adverse effects?

Abstract Esophageal and gastric cancers are aggressive diseases. Due to extensive treatment, many patients experience adverse effects such as dysphagia, dumping, pain, fatigue, fear of recurrence and depression—all negatively impacting quality of life (QoL). The purpose of this study is to develop and test a follow-up model for patients after surgery for esophageal and gastric cancer. The model targets handling of adverse effects and psychosocial distress, aiming at improving patients’ QoL and functional level. Methods Development of the model follows recognized principles for complex interventions by the Medical Research Counsil. Extensive patient involvement is included in the development process, by means of a national patient advisory board. The assumed effect of the new model will be tested in a national two-part prospective study, executed before and after national implementation of the model, in both parts including approximately200 patients. Participants will be recruited prior to surgery, and follow-up is one year. Patient-reported data will be collected pre-operatively, at 3, 6, 9 and 12 months postoperatively, along with clinical and sociodemographic data. Results Development of the follow-up model after surgery will be completed in august 2020 and inclusion of patients for the prospective study part one, before implementation of the model, will commence summer 2020. Conclusion The perspectives of this study may be crucial for future follow-up of esophageal and gastric cancer patients. First, the extensive patient involvement in developing the model will ensure a patient-centred approach to follow-up. And second, the follow-up studies will provide important and up-to-date knowledge about clinical and patient-reported outcomes in a population-based, national cohort.

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P01 An evaluation of vancomycin therapy in paediatric patients post guideline change

Archives of Disease in Childhood ◽

10.1136/archdischild-2020-nppg.10 ◽

2020 ◽

Vol 105 (9) ◽

pp. e6.1-e6 ◽

Cited By ~ 1

Author(s):

Adedoyin Agbonin ◽

Joanne Crook

Keyword(s):

Adverse Effects ◽

Renal Impairment ◽

Therapeutic Drug ◽

Drug Levels ◽

Paediatric Patients ◽

Patient Reported ◽

The Right ◽

Higher Doses ◽

Trough Levels ◽

Local Guideline

AimTo evaluate the prescribed dose of vancomycin as per local guideline and review the achieved therapeutic drug levels.MethodRetrospective data was collected from paediatric inpatients that were prescribed vancomycin for more than 24 hours during the audit period. Data was obtained from the Trust’s electronic prescribing system, LastWord. Measured standards included initial vancomycin dose, dose prescribed for renal impairment, time to first trough level and any required dose adjustments as per local guidance. The dose bands for each age group were1; birth - 6 months 15 mg/g 8 hourly; >6 months -12 months 20 mg/kg 8 hourly; >12 months – 12 years 25 mg/kg 8 hourly; >12 years 20 mg/kg 8 hourly. The number of patients achieving therapeutic vancomycin trough levels was recorded. Safety data was collected, including reported adverse effects, infusion related reactions and renal impairment. Renal impairment was defined as an increase in creatinine by 50%. Data was collected from April 2018 for 6 months. Relevant data with regards to patient demographics, dosing and drug levels were collected and analysed using Microsoft Excel.Results12 patients received 15 doses of vancomycin over 6 months. 67% of initial vancomycin doses were prescribed as per local guideline, 60% of therapeutic trough levels were taken at the right time and 71% of patients that were prescribed the correct dose and had levels taken at the right time achieved therapeutic trough levels. 12 patients required dose adjustments. One patient with renal impairment was not prescribed the recommended dose as per local guidance. One patient reported an infusion related reaction, which was overcome by increasing the infusion time. Two patients who received therapy for >7 days accumulated vancomycin and recorded high trough levels, with no adverse events. One patient reported an increase in creatinine by 50% over the treatment period.ConclusionsVancomycin has the potential to induce nephrotoxicity and ototoxicity when consistently at high serum drug levels. Due to its narrow therapeutic index, drug levels should be monitored to ensure the drug does not accumulate. The licensed dose and dose listed in the BNF for Children 2 3 has historically under dosed patients at our trust, leading to the risk of ineffective therapy and bacterial resistance. It is unclear from research what the optimal dose is for paediatric patients.More research is needed to determine the correct paediatric dose of vancomycin. Higher doses than currently recommended as per licence resulted in three quarters of patients achieving therapeutic levels, however 12 patients still required dose adjustment. No patients suffered irreversible adverse effects or toxicity, suggesting that higher doses are safe to use in the paediatric population. Further education is required for those involved in the prescribing, administering and monitoring of Vancomycin in paediatric patients to ensure its safe use. Additional monitoring is required for those receiving higher doses >7 days to prevent drug accumulation, alternatively a loading dose followed by lower maintenance dose may be a more suitable dosing regimen.ReferencesHughes S, Crook J, Ross J. Vancomycin intravenous dosing guideline - paediatrics. Chelsea and Westminster Hospital; 2017.Stockman C, Sammons H, Stakey E, et al. Unanswered Questions Regarding Optimal Pediatric Vancomycin Use. Therapeutic Drug Monitoring 2016; 38:491–420.National Institute for Health and Care Excellence. Vancomycin. Available from https://bnfc.nice.org.uk/drug/vancomycin.html [Accessed 10th Oct 2018]

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Patient-Reported Outcome Results From the Open-Label, Randomized Phase III Myeloma X Trial Evaluating Salvage Autologous Stem-Cell Transplantation in Relapsed Multiple Myeloma

Journal of Clinical Oncology ◽

10.1200/jco.18.01006 ◽

2019 ◽

Vol 37 (19) ◽

pp. 1617-1628 ◽

Cited By ~ 7

Author(s):

Sam H. Ahmedzai ◽

John A. Snowden ◽

Andrew John Ashcroft ◽

David Allan Cairns ◽

Cathy Williams ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Stem Cell ◽

Adverse Effects ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Random Assignment ◽

Time To Progression ◽

Patient Reported

PURPOSE Salvage autologous stem-cell transplantation (sASCT) in patients with multiple myeloma (MM) relapsing after a prior autologous stem-cell transplantation leads to increased remission duration and overall survival. We report a comprehensive study on patient-reported outcomes, including quality of life (QoL) and pain in sASCT. METHODS Patients were randomly assigned to either sASCT or nontransplantation consolidation (NTC). Pain and QoL were assessed as secondary outcomes using validated QoL instruments (European Organisation for Research and Treatment of Cancer QLQ-C30 and myeloma-specific module, QLQ-MY20; the Brief Pain Inventory [Short Form]; and the Leeds Assessment of Neuropathic Symptoms and Signs [Self-Assessment] scale). RESULTS A total of 288 patients (> 96%) consented to the QoL substudy. The median follow-up was 52 months. The European Organisation for Research and Treatment of Cancer QLQ-C30 Global health status scores were higher (better) in the NTC group at 100 days after random assignment ( P = .0496), but not at later time points. Pain interference was higher (worse) in the sASCT group than in the NTC group at 6 months after random assignment ( P = .0267), with patients with sASCT reporting higher scores for Pain interference with daily living for up to 2 years after random assignment. Patients reporting lower concerns about adverse effects of treatment after sASCT had a time to progression advantage. CONCLUSION Patients with sASCT with relapsed MM demonstrated a comparative reduction in QoL and greater impact of treatment adverse effects lasting for 6 months and up to 2 years for pain, after which patients who had received sASCT reported better outcomes. Patients who experienced lower adverse effects after sASCT had longer time to progression and overall survival, showing the need to improve symptom management peritransplantation. To our knowledge, this study provides the most comprehensive picture of QoL before and after sASCT in patients with relapsed MM.

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How good is physician reporting of chemotherapy adverse effects? A comparison to patient-reported symptoms from the QLQ-C30

Journal of Clinical Oncology ◽

10.1200/jco.2004.22.14_suppl.8022 ◽

2004 ◽

Vol 22 (14_suppl) ◽

pp. 8022-8022

Author(s):

E. K. Fromme ◽

K. M. Eilers ◽

M. Mori ◽

Y.-C. Hsieh ◽

T. M. Beer

Keyword(s):

Adverse Effects ◽

Patient Reported

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How good is physician reporting of chemotherapy adverse effects? A comparison to patient-reported symptoms from the QLQ-C30

Journal of Clinical Oncology ◽

10.1200/jco.2004.22.90140.8022 ◽

2004 ◽

Vol 22 (14_suppl) ◽

pp. 8022-8022

Author(s):

E. K. Fromme ◽

K. M. Eilers ◽

M. Mori ◽

Y.-C. Hsieh ◽

T. M. Beer

Keyword(s):

Adverse Effects ◽

Patient Reported

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A multidisciplinary clinic to mitigate the toxicity of therapy for newly diagnosed metastatic prostate cancer undergoing chemohormonal therapy: A feasibility study.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.5_suppl.153 ◽

2017 ◽

Vol 35 (5_suppl) ◽

pp. 153-153

Author(s):

Jeffrey Hough ◽

Tammy J. Rodvelt ◽

Miles Thomas ◽

Brian Ma ◽

Michael W. Rabow ◽

...

Keyword(s):

Prostate Cancer ◽

Adverse Effects ◽

Body Fat ◽

Metastatic Prostate Cancer ◽

Positive Impact ◽

Randomized Study ◽

Well Being ◽

Newly Diagnosed ◽

Chemohormonal Therapy ◽

Patient Reported

153 Background: Chemohormonal therapy is standard of care for newly diagnosed metastatic prostate cancer (mPC) patients (pts) but is associated with significant adverse effects and negative metabolic changes. We performed a pilot study to investigate whether participation in a multi-disciplinary clinic to mitigate adverse effects of treatment is feasible. Methods: Pts with recently diagnosed mPC who were planning to start or had recently started chemohormonal therapy were prospectively enrolled in a multi-disciplinary clinic that included individualized monthly counseling from a physical therapist, oncology dietitian, and palliative care specialist on a rotating basis for 12 months. Patients were assessed quarterly for changes in % body fat, weight, serum levels of 25-OH vitamin D, fasting lipids/glucose/insulin, and quality of life (QOL). DXA bone density scans were performed at baseline and end of 12 months. The primary endpoint was the completion rate of scheduled visits. Results: 7 pts were enrolled between September 2015 and June 2016. All patients had extensive disease ( > 4 bone metastases and/or visceral metastases) at the time of study entry, and all 7 patients completed six cycles of docetaxel-based chemotherapy, and remained on hormone therapy for the duration of study. The percentage of completed visits was 98% (54/55 planned visits). The percentage of completed assessments including QOL questionnaires was 81%. No skeletal-related complications were observed. Median percent increase from baseline in body weight and % body fat was 3.51% and 20%, respectively. Four of the seven patients had osteopenia at baseline. Patient reported satisfaction was high and positive impact on psychosocial well-being was observed. Conclusions: Participation in a multi-disciplinary clinic by men receiving intensive chemohormonal therapy for metastatic prostate cancer was feasible. Patients are at risk for adverse metabolic and bone toxicity with therapy, underscoring the potential positive impact of a multi-disciplinary clinic. A randomized study to detect objective improvements in health outcomes is underway. Clinical trial information: NCT02168062.

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Does co-administration of paroxetine change oxycodone analgesia: An interaction study in chronic pain patients

Scandinavian Journal of Pain ◽

10.1016/j.sjpain.2009.09.003 ◽

2010 ◽

Vol 1 (1) ◽

pp. 24-33 ◽

Cited By ~ 20

Author(s):

K.K. Lemberg ◽

T.E. Heiskanen ◽

M. Neuvonen ◽

V.K. Kontinen ◽

P.J. Neuvonen ◽

...

Keyword(s):

Chronic Pain ◽

Adverse Effects ◽

Opioid Receptor ◽

Placebo Administration ◽

Rescue Analgesia ◽

Analgesic Effects ◽

Patient Reported ◽

Chronic Pain Patients ◽

Μ Opioid Receptor ◽

Pain Patients

AbstractOxycodone is a strong opioid and it is increasingly used in the management of acute and chronic pain. The pharmacodynamic effects of oxycodone are mainly mediated by the μ-opioid receptor. However, its affinity for the μ-opioid receptor is significantly lower compared with that of morphine and it has been suggested that active metabolites may play a role in oxycodone analgesia. Oxycodone is mainly metabolized by hepatic cytochrome (CYP) enzymes 2D6 and 3A4. Oxycodone is metabolized to oxymorphone, a potent μ-opioid receptor agonist by CYP2D6. However, CYP3A4 is quantitatively a more important metabolic pathway. Chronic pain patients often use multiple medications. Therefore it is important to understand how blocking or inducing these metabolic pathways may affect oxycodone induced analgesia. The aim of this study was to find out whether blocking CYP2D6 would decrease oxycodone induced analgesia in chronic pain patients.The effects of the antidepressant paroxetine, a potent inhibitor of CYP2D6, on the analgesic effects and pharmacokinetics of oral oxycodone were studied in 20 chronic pain patients using a randomized, double-blind, placebo-controlled cross-over study design. Pain intensity and rescue analgesics were recorded daily, and the pharmacokinetics and pharmacodynamics of oxycodone were studied on the 7th day of concomitant paroxetine (20 mg/day) or placebo administration. The patients were genotyped for CYP2D6, 3A4, 3A5 and ABCB1.Paroxetine had significant effects on the metabolism of oxycodone but it had no statistically significant effect on oxycodone analgesia or use of morphine for rescue analgesia. Paroxetine increased the dose-adjusted mean AUC0–12h of oxycodone by 19% (−23 to 113%; P = 0.003), and that of noroxycodone by 100% (5–280%; P < 0.0001) but decreased the AUC0–12 h of oxymorphone by 67% (−100 to −22%; P < 0.0001) and that of noroxymorphone by 68% (−100 to −16%; P < 0.0001).Adverse effects were also recorded in a pain diary for both 7-day periods (placebo/paroxetine). The most common adverse effects were drowsiness and nausea/vomiting. One patient out of four reported dizziness and headache during paroxetine co-administration, whereas no patient reported these during placebo administration (P = 0.0471) indicating that these adverse effects were due to paroxetine.No statistically significant associations of the CYP2D6 or CYP3A4/5 genotype of the patients and the pharmacokinetics of oxycodone or its metabolites, extent of paroxetine–oxycodone interaction, or analgesic effects were observed probably due to the limited number of patients studied.The results of this study strongly suggest that CYP2D6 inhibition does not significantly change oxycodone analgesia in chronic pain patients and that the analgesic activity of oxycodone is mainly due to the parent compound and that metabolites, e.g. oxymorphone, play an insignificant role. The clinical implication of these results is that induction of the metabolism of oxycodone may lead to inadequate analgesia while increased drug effects can be expected after addition of potent CYP3A4/5 inhibitors particularly if combined with CYP2D6 inhibitors or when administered to poor metabolizers of CYP2D6.

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Adjuvant Ketamine Analgesia for the Management of Cancer Pain

Annals of Pharmacotherapy ◽

10.1345/aph.1a256 ◽

2002 ◽

Vol 36 (10) ◽

pp. 1614-1619 ◽

Cited By ~ 21

Author(s):

Angela L McQueen ◽

Steven A Baroletti

Keyword(s):

Adverse Effects ◽

Testicular Cancer ◽

Opioid Use ◽

Data Synthesis ◽

Medline Search ◽

Additional Information ◽

Patients With Cancer ◽

Lower Back ◽

Clinical Literature ◽

Patient Reported

OBJECTIVE: To review the clinical literature evaluating the utilization of intravenous ketamine for the management of cancer-related pain, to summarize the data that suggest ketamine is an appropriate adjuvant method of providing analgesia and to report a case of successful pain management using ketamine in a patient with recurrent testicular cancer at our institution. DATA SOURCES: Primary literature was identified through a MEDLINE search (1966–March 2002), and additional information was obtained through secondary and tertiary sources. DATA SYNTHESIS: The available data suggest that supplementation of morphine with ketamine improves analgesia in patients with cancer, and also provides insight to the controversy regarding the efficacy and adverse effects of various ketamine doses. At subanesthetic doses, ketamine may be beneficial at reducing opioid requirements and related adverse effects. CASE SUMMARY: A 34-year-old white man with recurrent testicular cancer was admitted with radiating neuropathic pain of the legs and lower back. The patient was suspected to also be experiencing opioid adverse effects; therefore, alternative analgesic options were warranted. Ketamine was successful in reducing patient-reported pain and was also well tolerated. CONCLUSIONS: Ketamine is an adjuvant analgesic for the treatment of cancer-related pain when other agents either fail or are intolerable. Accordingly, there are several factors that may prevent adequate pain control with opioid use; therefore, alternative analgesic options should be considered. Promise exists for ketamine as a contemporary analgesic in the appropriate patient.

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Topical Amitriptyline-Ketamine for Treatment of Rectal, Genital, and Perineal Pain and Discomfort

January 2018 - Pain Physician ◽

10.36076/ppj.2012/15/485 ◽

2012 ◽

Vol 6;15 (6;12) ◽

pp. 485-488

Author(s):

Mark D. P. Davis

Keyword(s):

Adverse Effects ◽

Pelvic Pain ◽

Retrospective Review ◽

Medical Records ◽

Academic Medical Center ◽

The United States ◽

High Rate ◽

Perineal Pain ◽

Complete Relief ◽

Patient Reported

Background: Pain in the rectal, genital, and perineal area is a common condition treated by pain physicians. These chronic pain syndromes are therapeutically challenging because both interventional and drug therapies often are ineffective. Objectives: To determine if pelvic pain can be treated effectively with compounded topical amitriptyline-ketamine. Study Design: A retrospective review of medical records. Setting: A single academic medical center in the United States. Methods: We identified all patients treated with topical amitriptyline-ketamine from January 1, 2004, through November 28, 2011. Medical records were evaluated to determine the diagnosis for which the medication was prescribed. Treatment efficacy and any adverse effects were recorded. Results: Of the 1,068 patients who received amitriptyline-ketamine, 13 had the medication prescribed for genital, rectal, or perineal pain and had medication efficacy recorded. These patients were treated with a topical combination of amitriptyline 1-2% and ketamine 0.5%. Of these 13 patients, one (8%) had complete relief, 6 (46%) had substantial relief, 4 (31%) had some relief, and 2 (15%) had no response. One patient reported occasional irritation while using topical amitriptyline-ketamine with lidocaine; no other patients reported local or systemic adverse effects. Limitations: Retrospective review; lack of uniform system for pain grading; concurrent use of other medications. Conclusions: Topical amitriptyline-ketamine provided a high rate of pain relief with a low adverse-effect burden in patients with pelvic pain. This topical medication could offer an effective, noninvasive, nonopioid therapy for pain in the rectum, perineum, and genitals. Key words: Amitriptyline, rectal, compounded medication, genital, ketamine, pain, pelvic, perineal.

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