This study investigated the efficacy and tolerability of wearing frozen gloves (FGs) during chemotherapy to prevent chemotherapy-induced peripheral neuropathy (CIPN) as reported by patients and ...influence on quality of life (QoL).
Cancer patients starting treatment with oxaliplatin, docetaxel or paclitaxel between February 2013 and May 2016 at the medical oncology department were eligible. Patients were randomized into groups wearing FGs on both hands during treatment and those not wearing FGs during treatment. Self-reported CIPN and QoL were measured with the European Organisation for the Research and Treatment of Cancer Quality of Life (EORTC QLQ) CIPN20 and QLQ-C30 at four time points: baseline (t0), after three cycles (t1), end of chemotherapy (t2) and after 6 months (t3).
The study included 180 patients with 90 patients in both arms. They mostly underwent treatment of colorectal or breast cancer. Thirty-one patients (34%) discontinued FGs, mainly due to discomfort. Intention-to-treat analyses showed no important differences in reported EORTC QLQ CIPN20 subscales between the FG group and control group; however, the analyses showed the patients experienced reduced tingling in fingers/hands β = −10.20, 95% confidence interval (CI) = −3.94 to −3.14, P = 0.005 and less trouble opening a jar or bottle due to loss of strength in hands (β = −6.97, 95% CI = −13.53 to −0.40, P = 0.04) in the FG group compared with the control group. Per-protocol analyses showed similar results: reduced aching or burning pain in fingers/hands (β = −4.37, 95% CI = −7.90 to −0.83, P = 0.02) and cramps in hands (β = −3.76, 95% CI = −7.38 to −0.14, P = 0.04). Differences in tingling in fingers/hands at t1 were clinically relevant. In addition, those treated with FGs reported overall better QoL (β = 4.79, 95% CI = 0.37 to 9.22, P = 0.03) and physical functioning (β = 5.66, 95% CI = 1.59 to 9.73, P = 0.007) than the control. No difference in dose reductions was observed.
No difference in CIPN subscales was reported between intervention arms. Wearing FGs might reduce some neuropathy symptoms in the hands, potentially resulting in a better QoL; however, one-third of the FG group discontinued the study before the end of treatment. Future studies should focus on the method of limb hypothermia to prevent CIPN.
NL39650.015.12.
•CIPN is a common side-effect of taxanes and oxaliplatin.•No improvement in CIPN-subscales was reported in patients wearing frozen gloves.•FGs reduce some neuropathy symptoms in hands potentially resulting in a better QOL.
Purpose
The aim of this study was to systematically review the literature on the influence of oxaliplatin administration (e.g. cumulative dose, dose intensity, number of cycles and combination ...regimen) on the long-term prevalence of oxaliplatin-induced peripheral neuropathy (O-IPN) at least 12 months after termination of chemotherapy.
Methods
A computerized search of literature on databases PubMed and Cochrane was performed. Published original articles were included if they reported about long-term O-IPN and gave concomitant information about oxaliplatin therapy given to the patients. All articles were assessed for quality.
Results
We included 14 articles (
n
= 3,869 patients), and the majority of these studies were of high quality. All included patients who were treated for colorectal cancer, mainly with oxaliplatin in combination with 5-fluorouracil/leucovorin. Median cumulative doses and dose intensity varied between 676 and 1,449 mg/m
2
and 30.8 and 42.6 mg/m
2
/week, respectively. Neuropathy assessment differed between studies, and the National Cancer Institute-Common Terminology Criteria (NCI-CTC) was used most often. The degree of neuropathy ranged from grade 0 to 3. Only six studies directly assessed the relationship between oxaliplatin administration and neuropathy. Of these studies, five did find a relation between neuropathy and higher cumulative dose, while one study did not find a relation.
Conclusions
O-IPN is still present in a great amount of patients in ≥12 months after termination of therapy. A higher cumulative dose is likely to have an influence on the development of long-term O-IPN. More studies are needed that assess long-term neuropathy and oxaliplatin administration by means of validated neuropathy assessments.
Purpose
This study aims to (1) examine the prevalence of painful versus non-painful chemotherapy-induced peripheral neuropathy (CIPN) among long-term colorectal cancer (CRC) survivors, (2) identify ...sociodemographic, clinical, and psychological factors associated with painful and non-painful CIPN, and (3) examine the associations of painful CIPN with health-related quality of life (HRQoL) in comparison with non-painful CIPN, i.e., numbness/tingling.
Methods
All CRC survivors diagnosed between 2000 and 2009 as registered by the population-based Netherlands Cancer Registry (Eindhoven region) were eligible for participation. Chemotherapy-treated survivors (
n
= 477) completed questions on CIPN (EORTC QLQ-CIPN20) and HRQoL (EORTC QLQ-C30).
Results
Painful CIPN was reported by 9% (
n
= 45) of survivors and non-painful CIPN was reported by 22% (
n
= 103). Time since diagnosis was related to painful CIPN, and time since diagnosis, a higher disease stage, osteoarthritis, and more anxiety symptoms were related to non-painful CIPN. Finally, survivors with painful CIPN reported a worse global quality of life and worse physical, role, cognitive, and social functioning compared to survivors with non-painful CIPN and those without any sensory CIPN. No differences were found between survivors with non-painful CIPN and those without sensory CIPN.
Conclusions
It seems that painful CIPN must be distinguished from non-painful CIPN, as only painful CIPN was related to a worse HRQoL. Future research is needed to examine whether painful CIPN must be distinguished from non-painful CIPN regarding predictors, mechanisms, and treatment.
The introduction of programmed cell death protein 1 (PD-1) blockers (i.e. nivolumab and pembrolizumab) has significantly improved the prognosis of patients with advanced melanoma. However, the long ...treatment duration (i.e. two years or longer) has a high impact on patients and healthcare systems in terms of (severe) toxicity, health-related quality of life (HRQoL), resource use, and healthcare costs. While durable tumour responses have been observed and PD-1 blockade is discontinued on an individual basis, no consensus has been reached on the optimal treatment duration. The objective of the Safe Stop trial is to evaluate whether early discontinuation of first-line PD-1 blockade is safe in patients with advanced and metastatic melanoma who achieve a radiological response.
The Safe Stop trial is a nationwide, multicentre, prospective, single-arm, interventional study in the Netherlands. A total of 200 patients with advanced and metastatic cutaneous melanoma and a confirmed complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumours (RECIST) v1.1 will be included to early discontinue first-line monotherapy with nivolumab or pembrolizumab. The primary objective is the rate of ongoing responses at 24 months after discontinuation of PD-1 blockade. Secondary objectives include best overall and duration of response, need and outcome of rechallenge with PD-1 blockade, and changes in (serious) adverse events and HRQoL. The impact of treatment discontinuation on healthcare resource use, productivity losses, and hours of informal care will also be assessed. Results will be compared to those from patients with CR or PR who completed 24 months of treatment with PD-1 blockade and had an ongoing response at treatment discontinuation. It is hypothesised that it is safe to early stop first-line nivolumab or pembrolizumab at confirmed tumour response while improving HRQoL and reducing costs.
From a patient, healthcare, and economic perspective, shorter treatment duration is preferred and overtreatment should be prevented. If early discontinuation of first-line PD-1 blockade appears to be safe, early discontinuation of PD-1 blockade may be implemented as the standard of care in a selected group of patients.
The Safe Stop trial has been registered in the Netherlands Trial Register (NTR), Trial NL7293 (old NTR ID: 7502), https://www.trialregister.nl/trial/7293 . Date of registration September 30, 2018.
Background The Multicenter Selective Lymphadenectomy Trial (MSLT-1) comparing survival after a sentinel lymph node biopsy (SLNB) versus nodal observation in melanoma patients did not show a ...significant benefit favoring SLNB. However, in subgroup analyses melanoma-specific survival among patients with nodal metastases seemed better. Aim To evaluate the association of performing a SLNB with overall survival in intermediate thickness melanoma patients in a Dutch population-based daily clinical setting. Methods Survival, excess mortality adjusted for age, gender, Breslow-thickness, ulceration, histological subtype, location, co-morbidity and socioeconomic status were calculated in a population of 1,989 patients diagnosed with malignant cutaneous melanoma (1.2-3.5 mm) on the trunk or limb between 2000-2016 in ten hospitals in the South East area, The Netherlands. Results A SLNB was performed in 51% of the patients (n = 1008). Ten-year overall survival after SLNB was 75% (95%CI, 71%-78%) compared to 61% (95%CI 57%-64%) following observation. After adjustment for risk factors, a lower risk on death (HR = 0.80, 95%CI 0.66-0.96) was found after SLNB compared to observation only. Conclusions SLNB in patients with intermediate-thickness melanoma on trunk or limb resulted in a 14% absolute and significant 10-year survival difference compared to those without SLNB.
•Current anticancer drug trial designs are often not suitable to determine an optimal efficacy threshold.•This implies potential overtreatment with unnecessary toxicities and undermines the success ...rates of trials.•De-escalation non-inferiority trials require considerable resources and time.•We propose a new Framework for Cautious Escalation for clinical trials in oncology.•The FCE may prevent overtreatment, optimize use of resources and obviate the need for de-escalation trials.
The developmental workflow of the currently performed phase 1, 2 and 3 cancer trial stages lacks essential information required for the determination of the optimal efficacy threshold of new anticancer regimens. Due to this there is a serious risk of overdosing and/or treating for an unnecessary long time, leading to excess toxicity and a higher financial burden for society. But often post-approval de-escalation trials for dose-optimization and treatment de-intensification are not performed due to failing resources and time. Therefore, the developmental workflow needs to be restructured toward cautious systemic cancer treatment escalation, in order to guarantee optimal efficacy and sustainability.
In this manuscript we discuss opportunities to produce the information needed for cautious escalation, based on models of cancer growth and cancer kill kinetics as well as exploratory biomarkers, for the purpose of designing the optimal phase 3 superiority trial. Subsequently, we compare the sample size needed for a phase 3 superiority trial, followed by a necessary de-escalation trial with the sample size needed for a multi-arm phase 3 trial with intervention arms of differing intensity. All essential items are structured within a Framework for Cautious Escalation (FCE). The discussion uses illustrations from the breast cancer setting, but aims to be applicable for all cancers.
The FCE is a promising model of clinical development in oncology to prevent overtreatment and associated issues, especially with regard to the number of repetitive treatment cycles. It will hopefully increase the relevance and success rate of clinical trials, to deliver improved patient-centric outcomes.
Chemotherapy-induced peripheral neuropathy (CIPN) is a common major dose-limiting side effect of many chemotherapeutic agents, including platinum compounds, taxanes, vinca alkaloids, thalidomide and ...newer agents such as bortezomib. The incidence and degree of neuropathy depends on the type of cytotoxic drug, the duration of administration, cumulative dose and pre-existing peripheral neuropathy. Because of increasing survival rates of patients treated with neurotoxic agents, CIPN is accompanied by a significant decrease in the patient's quality of life among cancer survivors. Therefore, several neuroprotective strategies, including calcium/magnesium infusion, amifostine, gluthatione, glutamine, acetyl-L-carnitine and erythropoietin as most promising, have been investigated to decrease the neurotoxicity without compromising anti-tumour efficacy. However, clinical evidence for the efficacy of these drugs is sparse. In this review we will give an outline of the neurotoxic effects of chemotherapeutic agents, their clinical manifestations and potential neuroprotective strategies.
Patients with irresectable stage III or metastatic melanoma presenting with poor prognostic factors are usually treated with a combination of immune checkpoint inhibitors (ICIs), consisting of ...ipilimumab and nivolumab. This combination therapy is associated with severe immune related adverse events (irAEs) in about 60% of patients. In current clinical practice, patients are usually treated with ICIs for up to two years or until disease progression or the occurrence of unacceptable AEs. The incidence of irAEs gradually increases with duration of treatment. While durable tumour responses have been observed after early discontinuation of treatment, no consensus has been reached on optimal treatment duration. The objective of the Safe Stop IPI-NIVO trial is to evaluate whether early discontinuation of ICIs is safe in patients with irresectable stage III or metastatic melanoma who are treated with combination therapy.
The Safe Stop IPI-NIVO trial is a nationwide, multicentre, prospective, single-arm, interventional study in the Netherlands. A total of 80 patients with irresectable stage III or metastatic melanoma who are treated with combination therapy of ipilimumab-nivolumab and have a complete or partial response (CR/PR) according to RECIST v1.1 will be included to early discontinue maintenance therapy with anti-PD-1. The primary endpoint is the rate of ongoing response at 12 months after start of ICI. Secondary endpoints include ongoing response at 24 months, disease control at different time points, melanoma specific and overall survival, the incidence of irAEs and health-related quality of life.
From a medical, healthcare and economic perspective, overtreatment should be prevented and shorter treatment duration of ICIs is preferred. If early discontinuation of ICIs is safe for patients who are treated with the combination of ipilimumab-nivolumab, the treatment duration of nivolumab could be shortened in patients with a favourable tumour response.
ClinicalTrials.gov ID NCT05652673, registration date: 08-12-2022.
This systematic review summarizes the research of previous studies that used resistance training in the post-treatment phase of cancer patients with a focus on methodological quality, training ...methods and physical outcome measures. We found twenty-four studies (10 RCTs, 4 controlled clinical trials and 10 uncontrolled trials) that met all inclusion criteria. The studies were of moderate methodological quality. The majority of studies involved breast cancer patients (54%), followed by prostate cancer patients (13%). Most studies used a combination of resistance and aerobic training, which was mostly supervised. Resistance training involved large muscle groups, with 1-3 sets of 8-12 repetitions. The duration of the resistance training programs varied from 3-24 weeks, with a training frequency of 1-5 sessions per week. The training intensity ranged from 25% to 85% of the one-repetition maximum. Overall, positive training effects were observed for cardiopulmonary and muscle function, with significant increases in peak oxygen uptake (range: 6-39%), and in the one-repetition maximum (range: 11-110%). In general, there were no effects of training on body composition, endocrine and immune function, and haematological variables. No adverse effects of the resistance training were reported. Based upon these results, we recommend to incorporate resistance training in cancer rehabilitation programmes.
Purpose
To assess perception of prognosis in patients with advanced cancer, its association with patient’s characteristics and health-related quality of life (HRQoL).
Methods
In a multicentre ...observational cohort study (eQuiPe), conducted on patients with advanced cancer, perceived prognosis, coping strategies, and HRQoL were assessed. Clinical data were obtained from the Netherlands Cancer Registry. Patients with vs. without a perception of prognosis, patients who perceived their prognosis as limited (< 1 year) vs. longer (> 1 year), and patients who did not want to know their prognosis vs. those who did not know for other reasons were compared.
Results
Of 1000 patients with advanced cancer, 29% perceived their prognosis as > 1 year, 13% < 1 year, and 4% non-life threatening. Thirty-six percent did not know their prognosis and another 15% did not want to know. Patients without a perception were older, lower educated, coped differently (less accepting, planning, active; more denial), and received treatment more often (
p
< 0.05). Global QoL was lower in patients with vs. without a perceived prognosis (66 (SD21) vs. 69 (SD19),
p
= 0.01), specifically in patients who perceived a limited rather than a longer prognosis (57 (SD22) vs. 70 (SD19),
p
< 0.01). Global QoL of patients who did not want to know their prognosis was comparable to patients who did not know for other reasons (71 (SD19) vs. 69 (SD19),
p
= 0.22).
Conclusion
More than half of the patients with advanced cancer have no perception of their prognosis. Patients with a perceived prognosis have lower HRQoL, but only in patients who perceived their prognosis as limited (< 1 year) and were probably closer to the end of life, which more likely determines their poorer HRQoL, rather than prognostic perception. Ignorance of prognosis is not associated with lower HRQoL, however, should not hamper appropriate palliative care.
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