Background & Aims
Chemotherapy induced peripheral neuropathy (CIPN) is a prevalent (30%-68%) and serious side effect of neurotoxic chemotherapy potentially impacting patient survival, and adversely affecting quality of life (1,2). It is characterised by symptoms such as tingling, numbness, and pain in the hands/feet which can be acute or chronic. Patients may be cured of their cancer, but chronic CIPN is more likely to be persistent (1). Although CIPN is widely acknowledged as a serious clinical problem, there are still no therapeutic options available to prevent CIPN (3). Ongoing clinical trials are vital resources for identifying evidence-based recommendations, but they are rarely included in systematic reviews (SRs) (4). Data from unpublished trials is also excluded from SRs (4). The aim of this study is to appraise available therapies from clinical trial registries using a systematic review approach to prevent CIPN in adult patients undergoing chemotherapy for the treatment of cancer.
Methods
This systematic review (SR) was prospectively registered on PROSPERO, ID: CRD42023429136. Studies included in this review were observational and experimental studies, ongoing clinical trials, and unpublished studies. Preclinical studies, any studies not published in English, and studies with patients under the age of 18 were excluded. The focus of this abstract is to specially provide an update on ongoing clinical trials, and unpublished studies to highlight the emerging pharmacological and non-pharmacological treatment strategies to prevent CIPN. Prior SRs in this area have focused only on randomised controlled trials. BT, AC and MG screened the titles and abstracts of the identified records on Covidence, and any conflicts were resolved by LC. BT and AC independently assessed the risk of bias for all the ongoing clinical trials and unpublished studied included in the review using a modified NIH quality assessment item tool.
Results
100 ongoing clinical trials (n=21 currently recruiting and n=17 not recruiting), unpublished studies (n=42 completed recruiting, n=7 terminated/suspended) and three studies with their status being unknown were identified. These studies were registered on 10 different clinical trial registries including ClinicalTrials.gov, and EU Clinical Trials Register. Additionally, 53 studies were in the areas of pharmacological management to prevent CIPN (including duloxetine, metformin, melatonin, acetyl carnitine, n-acetylcysteine, and glutamine). Furthermore, 47 studies examined the use of non-pharmacological approaches (including compression, cryotherapy, frozen gloves, exercise, vitamins B6/B12, and acupuncture). The assessment of risk of bias demonstrated 93% agreement between the two assessors (BT and AC) with majority of the studies being of either ‘good’ or ‘fair’ quality. Lack of funding, low recruitment and adverse drug related events were causes for studies being terminated early.
Conclusions
This is the first study that included data from ongoing clinical trials and unpublished studies as part of a SR to evaluate therapeutic options to prevent CIPN in patients undergoing neurotoxic chemotherapy to treat cancer. Typically, only clinical trials with positive results, large effect sizes get published and data from unpublished studies is omitted from SRs which contributes to research bias. Hunter et al. recently published guidelines on searching for registered studies and including them in SRs (5) which should be used in future studies. Reviewing the evidence from clinical trial registries is critical as it can assist in decision making about whether additional studies are needed in a particular area and can also help synthesize the evidence to avoid publication bias and duplication of the same studies. Additionally, the reporting of results and data regarding causes for early termination of clinical trials can inform development and planning of future studies to prevent CIPN.
References
1.Seretny M, Currie GL, Sena ES, et al. Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: a systematic review and meta-analysis. Pain 2014; 155:2461–70.
2.Colvin, Lesley A. Chemotherapy-induced peripheral neuropathy: where are we now? PAIN 160:p S1-S10, May 2019.
3.Loprinzi CL, Lacchetti C, Bleeker J, et al. Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: ASCO guideline update. J Clin Oncol 2020; 38:3325–48.
4.Lefebvre C, Manheimer E, Glanville J. Chapter 6.2.3: Unpublished and ongoing studies. In: Higgins JP, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration. 2011. [cited 2023 Jan 24].
5.Hunter K E, Webster A C, Page M J, Willson M, McDonald S, Berber S et al. Searching clinical trials registers: guide for systematic reviewers BMJ 2022; 377 :e068791
Presenting Author
Bhushan Thakkar
Poster Authors
Topics
- Specific Pain Conditions/Pain in Specific Populations: Cancer Pain & Palliative Care