Evaluation of the effect of intravenous calcium and magnesium (CaMg) on chronic and acute neurotoxicity associated with oxaliplatin: Results from a placebo-controlled phase III trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4025-4025
Author(s):  
A. Grothey ◽  
D. A. Nikcevich ◽  
J. A. Sloan ◽  
J. W. Kugler ◽  
P. T. Silberstein ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Acute Effect ◽  
Patient Reported Outcome ◽  
Phase Iii ◽  
Muscle Cramps ◽  
Patient Reported ◽  
Blinded Manner ◽  
Acute Neurotoxicity ◽  
Double Blinded ◽  
Dose Limiting Toxicity

4025 Background: Cumulative sNT is the dose-limiting toxicity of oxaliplatin which commonly leads to early discontinuation of oxaliplatin-based therapy in the palliative and adjuvant setting. We recently demonstrated the protective effect of CaMg against oxaliplatin-induced sNT as assessed by NCI-CTC (Nikcevich ASCO 2008). It is unclear, though, if CaMg reduced acute and/or chronic, cumulative sNT. Methods: 104 pts with colon cancer undergoing adjuvant therapy with FOLFOX were randomized to IV CaMg (1g calcium gluconate plus 1g magnesium sulfate pre- and post-oxaliplatin) or placebo (PL) in a double-blinded manner. NCI-CTC, an oxaliplatin-specific sNT scale and patient-reported outcome (PRO) questionnaires were used to differentially assess the effect of CaMg on acute (effect on sNT on days 1–4 after oxaliplatin) and chronic sNT (area between curves over whole course of therapy). Results: A total of 102 pts (50 CaMg, 52 PL; 96 mFOLFOX6, 6 FOLFOX4) were available for analysis. Apart from a strong reduction in muscle cramps with CaMg (p=0.002), no difference was found between CaMg and PL in PRO with regard to items reflecting acute sNT (e.g. sensitivity to cold, swallowing of cold liquids, throat discomfort) on days 1–4 after oxaliplatin of any treatment cycle. In contrast, CaMg was able to significantly reduce cumulative sNT in form of numbness in fingers (p=0.02), impaired ability to button shirts (p=0.05), tingling in fingers (p=0.06), and muscle cramps over the course of therapy (p=0.01). Conclusions: In our phase III, placebo-controlled trial, CaMg was able to significantly reduce chronic, cumulative sNT related to oxaliplatin as evaluated by specific PRO questionnaires. No effect was noted on phenomena associated with acute sNT. CaMg can be recommended as neuroprotectant against oxaliplatin-related chronic sNT, oxaliplatin's dose-limiting toxicity. [Table: see text]

scholarly journals Single postoperative infusion of zoledronic acid to improve patient-reported outcome after hip or knee replacement: study protocol for a randomised, controlled, double-blinded clinical trial

BMJ Open ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. e040985
Author(s):  
Jonathan Brandt ◽  
Håkan Ledin ◽  
Jonas Ranstam ◽  
Ewa Roos ◽  
Per Aspenberg ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Zoledronic Acid ◽  
Knee Replacement ◽  
Knee Prosthesis ◽  
Patient Reported Outcome ◽  
Ethical Review ◽  
Outcome Score ◽  
Patient Reported ◽  
Double Blinded ◽  
Improve Patient

IntroductionIn Sweden, roughly 3000 patients are reoperated each year due to pain and loss of function related to a loosened hip or knee prosthesis. These reoperations are strenuous for the patient, technically demanding and costly for the healthcare system. Any such reoperation that can be prevented would be of great benefit. Bisphosphonates are drugs that inhibit osteoclast function. Several clinical trials suggest that bisphosphonates lead to improved implant fixation and one small study even indicates better functional outcome. Furthermore, in epidemiological studies, bisphosphonates have been shown to decrease the rate of revision for aseptic loosening by half. Thus, there are several indirect indications that bisphosphonates could improve patient-reported outcome, but no firm evidence.Methods and analysisThis is a pragmatic randomised, placebo-controlled, double-blinded, academic clinical trial of a single postoperative dose of zoledronic acid, in patients younger than 80 years undergoing primary total hip or knee replacement for osteoarthritis. Participants will be recruited from two orthopaedic departments. All surgeries will be performed, and study drugs given at Motala Hospital, Sweden. The primary endpoint is to investigate between-group differences in the Hip dysfunction and Osteoarthritis Outcome Score and the Knee injury and Osteoarthritis Outcome Score at 3-year follow-up. Secondary outcomes will be investigated at 1 year, 3 years and 6 years, and stratified for hip and knee implants. These secondary endpoints are supportive, exploratory or explanatory. A total of 1000 patients will be included in the study.Ethics and disseminationThe study has been approved by the Regional Ethical Review Board in Linköping (DNR 2015/286-31). The study will be reported in accordance with the Consolidated Standards of Reporting Trials statement for pharmacological trials. The results will be submitted for publication in peer-reviewed academic journals and disseminated to patient organisations and the media.Trial registration numberEudraCT: No 2015-001200-55; Pre-results.

scholarly journals Intravenous Calcium and Magnesium for Oxaliplatin-Induced Sensory Neurotoxicity in Adjuvant Colon Cancer: NCCTG N04C7

2011 ◽  
Vol 29 (4) ◽  
pp. 421-427 ◽  
Author(s):  
Axel Grothey ◽  
Daniel A. Nikcevich ◽  
Jeff A. Sloan ◽  
John W. Kugler ◽  
Peter T. Silberstein ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Statistical Power ◽  
Early Discontinuation ◽  
Patient Questionnaires ◽  
Blinded Manner ◽  
Calcium Magnesium ◽  
Muscle Spasms ◽  
Double Blinded ◽  
Dose Limiting Toxicity ◽  
Intravenous Calcium

Purpose Cumulative sensory neurotoxicity (sNT) is the dose-limiting toxicity of oxaliplatin, which commonly leads to early discontinuation of oxaliplatin-based therapy in the palliative and adjuvant settings. In a nonrandomized, retrospective study, intravenous (IV) calcium/magnesium (Ca/Mg) was associated with reduced oxaliplatin-induced sNT. Methods Patients with colon cancer undergoing adjuvant therapy with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) were randomly assigned to Ca/Mg (1g calcium gluconate plus 1g magnesium sulfate pre- and post-oxaliplatin) or placebo, in a double-blinded manner. The primary end point was the percentage of patients with grade 2 or greater sNT at any time during or after oxaliplatin-based therapy by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; version 3) criteria. An oxaliplatin-specific sNT scale and patient questionnaires were also used to assess sNT. After 104 of 300 planned patients were enrolled, the study was closed. This was due to preliminary reports from another trial that suggested that Ca/Mg decreased treatment efficacy; these data were subsequently found to be incorrect. Results Overall, 102 patients were available for analysis. Ca/Mg decreased the incidence of chronic, cumulative, grade 2 or greater sNT, as measured by NCI CTCAE (P = .038) and also by the oxaliplatin-specific sNT scale (P = .018). In addition, acute muscle spasms associated with oxaliplatin were significantly reduced (P = .01) No effect on acute, cold-induced sNT was found. No substantial differences in adverse effects were noted between Ca/Mg and placebo. Conclusion Despite early termination and decreased statistical power, this study supports IV Ca/Mg as an effective neuroprotectant against oxaliplatin-induced cumulative sNT in adjuvant colon cancer.

scholarly journals Development of a patient-reported outcome questionnaire for aplastic anemia and paroxysmal nocturnal hemoglobinuria (PRO-AA/PNH)

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Kimmo Weisshaar ◽  
Hannah Ewald ◽  
Jörg Halter ◽  
Sabine Gerull ◽  
Sandra Schönfeld ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Patient Reported Outcome ◽  
Phase Iii ◽  
Specific Patient ◽  
Patient Reported ◽  
Related Quality ◽  
Health Related ◽  
Core Symptoms ◽  
Missing Items

Abstract Background The introduction of new therapy modalities has significantly improved the outcome of aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH) patients. However, relatively little is known about the exact disease burden of AA/PNH since standardized assessments of symptoms including health-related quality of life (HRQoL) are frequently missing or inadequately designed for this rare patient group. We aimed to develop AA/PNH-specific questionnaires for self-reporting of symptoms, which could be included in electronic platforms for data collection and patient care. Methods By scoping review, we extracted any reported symptoms in AA/PNH and their prevalence from the literature (Phase I). Consensus rounds with patients and medical experts were conducted to identify core symptoms reported in the literature and to add missing items (Phase II). Ultimately, AA/PNH-specific patient-reported outcome (PRO) questionnaires including the selected measures were designed (Phase III). Results AA symptoms from 62 and PNH symptoms from 45 observational studies were extracted from the literature. Twenty-four patients and seven medical experts identified 11 core symptoms including HRQoL issues after three consensus rounds. Significant differences in the symptom ranking of patients versus medical experts could be observed. Therefore, patient- as well as expert-centered PRO questionnaires in AA and PNH were created following the concepts of validated instruments. Conclusion The development of symptom self-reporting questionnaires for AA and PNH was feasible and the disease-specific PRO questionnaires can now be validated within a web-based workflow in a subsequent feasibility study.

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