Despite remarkable treatment advances in childhood cancer in the past few decades that have resulted in a survival rate of more than 80% for childhood cancers in high-income countries, the survival rate among children with cancer in low- and middle-income countries can be as low as 10% in some settings,¹ with a wide variability in survival by cancer type. Limited options usually remain when the malignant tumor progresses after 1 or 2 lines of a standard chemotherapy protocol. Repetitive administration of conventional chemotherapy at the maximum tolerated dose imposes many adverse effects that further limit dosing and quality of life. The goal of the oncologist at this point remains mainly palliative, with an effort to halt the progression of cancer and improve quality of life. Often the only therapy offered is best supportive care, which includes treatment of pain and other associated problems without any definite therapy for cancer control.

PURPOSE: Hand-foot syndrome (HFS) is a dose-limiting side effect of capecitabine. Celecoxib prevents HFS by inhibiting cyclooxygenase-2 (COX-2) that is upregulated because of the underlying associated inflammation. However, systemic side effects of celecoxib have limited routine prescription. Topical diclofenac inhibits COX-2 locally with minimal risk of systemic adverse events. Therefore, we conducted this study to assess the efficacy of topical diclofenac in the prevention of capecitabine-induced HFS. METHODS: In this single-site phase III randomized double-blind trial, we enrolled patients with breast or GI cancer who were planned to receive capecitabine-based treatment. Participants were randomly assigned in a 1:1 ratio to receive topical diclofenac or placebo gel for 12 weeks or until the development of HFS, whichever occurred earlier. The primary end point was the incidence of grade 2 or 3 HFS (Common Terminology Criteria for Adverse Events version 5), which was compared between the two groups using simple logistic regression. RESULTS: In total, 264 patients were randomly assigned to receive topical diclofenac gel (n = 131) or placebo (n = 133). Grade 2 or 3 HFS was observed in 3.8% of participants in the diclofenac group compared with 15.0% in the placebo group (absolute difference, 11.2%; 95% CI, 4.3 to 18.1; P = .003). Grade 1-3 HFS was lower in the diclofenac group than in the placebo group (6.1% v 18.1%; absolute risk difference, 11.9%; 95% CI, 4.1 to 19.6). Capecitabine dose reductions because of HFS were less frequent in the diclofenac group (3.8%) than in the placebo group (13.5%; absolute risk difference, 9.7%; 95% CI, 3.0 to 16.4). CONCLUSION: Topical diclofenac prevented HFS in patients receiving capecitabine. This trial supports the use of topical diclofenac to prevent capecitabine-associated HFS.

Background: Baseline cardiovascular disease (CVD) can impact the patterns of treatment and hence the outcomes of patients with lung cancer. This study aimed to characterize treatment trends and survival outcomes of patients with pre-existing CVD prior to their diagnosis of lung cancer. Methods: We conducted a retrospective, population-based cohort study of patients with lung cancer diagnosed from 2004 to 2015 in a large Canadian province. Multivariable logistic regression and Cox regression models were constructed to determine the associations between CVD and treatment patterns, and its impact on overall (OS) and cancer-specific survival (CSS), respectively. A competing risk multistate model was developed to determine the excess mortality risk of patients with pre-existing CVD. Results: A total of 20,689 patients with lung cancer were eligible for the current analysis. Men comprised 55%, and the median age at diagnosis was 70 years. One-third had at least one CVD, with the most common being congestive heart failure in 15% of patients. Pre-existing CVD was associated with a lower likelihood of receiving chemotherapy (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.48–0.58; P < .0001), radiotherapy (OR, 0.76; 95% CI, 0.7–0.82; P < .0001), and surgery (OR, 0.56; 95% CI, 0.44–0.7; P < .0001). Adjusting for measured confounders, the presence of pre-existing CVD predicted for inferior OS (hazard ratio [HR], 1.1; 95% CI, 1.1–1.2; P < .0001) and CSS (HR, 1.1; 95% CI, 1.1–1.1; P < .0001). However, in the competing risk multistate model that adjusted for baseline characteristics, prior CVD was associated with increased risk of non-cancer related death (HR, 1.48; 95% CI, 1.33–1.64; P < 0.0001) but not cancer related death (HR, 0.98; 95% CI, 0.94–1.03; P = 0.460). Conclusions: Patients with lung cancer and pre-existing CVD are less likely to receive any modality of cancer treatment and are at a higher risk of non-cancer related deaths. As effective therapies such as immuno-oncology drugs are introduced, early cardio-oncology consultation may optimize management of lung cancer.

Carboplatin increases the pathological complete remission (pCR) rate in triple negative breast cancer (TNBC) when added to neoadjuvant chemotherapy, however, evidence on its effect on survival outcomes is controversial. The study was prospectively registered at PROSPERO (CRD42021228386). We systematically searched PubMed, Embase, Cochrane Central Register of Clinical Trials, and conference proceedings from January 1, 2004 to January 30, 2022 for relevant randomized clinical trials (RCTs) of (neo)adjuvant chemotherapy in TNBC patients, with carboplatin in the intervention arm and standard anthracycline taxane (AT) in the control arm. PRISMA guidelines were used for this review. Data were pooled using fixed and random effects models as appropriate on extracted hazard ratios (HR). Individual patient data (IPD)for disease free survival (DFS) and overall survival (OS) were extracted from published survival curves of included RCTs; DFS and OS curves for each trial and the combined population were reconstructed, and HR estimated. The primary outcome was DFS; OS, pCR, and toxicity were secondary outcomes. Eight trials with 2425 patients were included. Carboplatin improved DFS (HR 0.60; 95% CI 0.47 to 0.78; I² 45%, p < 0.001) compared with AT at trial level and IPD level (HR 0.66; 95%CI, 0.55 to 0.80, p < 0.001) analysis. The OS also improved with carboplatin at both trial level (HR 0.69, 95%CI 0.50 to 0.95, I² 41%, p = 0.02) and IPD level (HR 0.68; 95%CI, 0.54 to 0.87, p = 0.002) analysis. The pCR as expected, was better in the carboplatin arm (OR 2.11; 95% CI = 1.44–3.08; I² 67%, p = 0.009). Anaemia and thrombocytopaenia were higher in the carboplatin arm. and relevance: Carboplatin added to (neo)adjuvant chemotherapy in TNBC improves survival, as shown in both trial level and IPD analysis.