Introduction Hand-foot syndrome (HFS) is a common cutaneous side effect of capecitabine therapy. Apart from oral cyclooxygenase-2 (COX-2) inhibitor (celecoxib), there are no proven strategies for the prevention of HFS. However, celecoxib is associated with significant cardiotoxicity. To date, no study has evaluated the role of topical COX inhibitor, diclofenac. In this study, we aim to compare topical 1% diclofenac gel with placebo in the prevention of capecitabine-induced HFS. Methods This is a randomized, placebo-controlled, double-blind, parallel-group superiority trial: the Diclofenac Topical in Reducing Capecitabine induced HFS (D-TORCH) study. A total of 264 patients with breast and gastrointestinal malignancies will be randomly allocated (stratified by sex and type of therapy [monotherapy or combination regimen with capecitabine]) to receive either 1% topical diclofenac or placebo that will be applied over the palmar and dorsal surface of the hands twice daily whilst taking capecitabine for 12 weeks. The patients will be followed up until the end of four cycles. The primary objective of this study is to compare the effect of topical diclofenac with placebo in preventing HFS (incidence of NCI CTCAEv5.0 grade 2 or higher HFS). The secondary objective is to compare the effect of topical diclofenac with placebo on preventing all grades of HFS (incidence of NCI CTCv5.0 all grade HFS), time to develop HFS (from the start of capecitabine), patient-reported outcomes (PROs) (HF-HRQoL questionnaire), adherence with the application (self-reported), capecitabine dose changes (number of patients with dose modifications due to HFS) and safety profile (NCICTCv5.0 all grade HFS) Discussion The D-TORCH study aims to determine if 1% topical diclofenac reduces the incidence of grade 2 or higher HFS in patients receiving capecitabine. To date, there have been a lot of trials for hand-foot syndrome prevention using agents like pyridoxine, vitamin E, carvedilol, and various polyherbal formulations, but none has been found successful. If the trial meets the primary end point, 1% topical diclofenac will be the new standard of care for HFS prevention. Trial registration Clinical Trials Registry of India CTRI/2021/01/030592. Prospectively registered on January 19, 2021
18 Background: Hand foot syndrome (HFS) is a dose-limiting side effect of capecitabine in patients with breast cancer. Celecoxib, an oral cyclo-oxygenase-2 (COX-2) inhibitor is effective in reducing the incidence of capecitabine associated HFS. However, it has not been adopted in the clinics due to concerns regarding cardiac and gastrointestinal toxicity. We report the efficacy of topical diclofenac in prevention of capecitabine associated HFS in patients with breast cancer. Methods: In the D-ToRCH (Diclofenac-topical for reduction of capecitabine related HFS) trial, we randomized 264 patients with breast or gastrointestinal cancers planned to receive capecitabine to apply either 1% topical diclofenac or placebo gel. Stratified (male or female; capecitabine monotherapy or combination therapy), permuted variable size block randomization was done using a computer-generated random numbers sequence. The primary objective was to compare the incidence of grade 2 or higher HFS in diclofenac and placebo arms. Secondary objectives were incidence of any grade HFS, capecitabine dose reductions due to HFS and self-reported adherence with application. Here, we report the exploratory subgroup analysis of patients with breast cancer. Results: The breast cancer subgroup included 148 patients (77 in drug arm and 71 in placebo arm). Baseline characteristics were similar in both arms. Median age of overall population was 47 years (IQR 39-56). 89 patients (60.1%) had an ECOG (Eastern Co-operative Oncology Group) performance status of 0-1, while the rest had a score of 2. Hypothyroidism was the most common comorbidity (n=24, 16.2%). Majority received capecitabine monotherapy (n=95, 64.2%). The most common additional chemotherapy drug used was lapatinib (n=42, 79.3%). 60 patients had stage 3 disease (40.8%) and 88 patients had metastatic breast cancer (59.5%). Overall, 20 patients developed any grade HFS, of which 6 were in the diclofenac arm and 14 in placebo arm (7.8% vs 19.7%, p=0.034). Grade 2/3 HFS events were noted in 3 patients (3.9%) in diclofenac arm and 11 patients (15.5%) in placebo arm (p=0.016). Capecitabine dose reductions were less frequent in the diclofenac arm compared to placebo (3.9% vs 15.5%). Adherence to topical treatment was similar in both the study arm. Other adverse events of capecitabine like diarrhea, mucositis and myelosuppression were similar in both the arms. Conclusions: Topical diclofenac gel significantly reduced the incidence of all grades of HFS in breast cancer patients receiving capecitabine. Applying topical diclofenac led to less frequent capecitabine dose reductions. Moving forward, we feel this should be the new standard of care and use of topical diclofenac should be regularized in medical oncology outpatient departments. Clinical trial information: CTRI/2021/01/030592 .
12005 Background: Capecitabine induced HFS is associated with deterioration of quality of life of patients and dose of capecitabine is often reduced to manage this adverse event. Celecoxib is the only effective intervention in preventing HFS; however, its widespread use is limited due to its own safety concerns. We conducted this study to assess the efficacy of topical diclofenac in preventing capecitabine induced HFS. Methods: Patients with breast and gastrointestinal (GI) cancers, planned for capecitabine (monotherapy or combination) treatment were randomized in 1:1 to receive topical diclofenac or placebo gel for 4 cycles or until development of HFS, whichever was earlier. Stratified (male or female; capecitabine monotherapy or combination therapy) permuted variable size block randomization was done using a computer-generated random numbers sequence. Primary objective was to compare the incidence of grade 2 or higher HFS in diclofenac and placebo arms. Secondary objectives were incidence of any grade HFS, capecitabine dose changes due to HFS and self-reported adherence with application. Results: A total of 263 patients were randomized to apply topical diclofenac gel (n=130) or placebo (n=133). Baseline characteristics were similar in both the arms (Table). The incidence of grade 2 or higher HFS was 3.8% (95% CI, 1.6%-8.9%) in the diclofenac arm compared with 15.0% (95% CI, 9.9%-22.2%) in the placebo arm (P=0.003). Any grade HFS was significantly lower in the study arm compared with the placebo arm (6.1% vs 18.1%; P=0.003). A lower incidence of HFS was observed in the diclofenac arm across the subgroups (breast and GI cancers; males and females). Capecitabine dose reductions were less frequent in the diclofenac arm (3.8%) compared with the placebo arm (15%) (P=0.002). Adherence to topical treatment was similar in the diclofenac arm (96.7 +/- 19.1%) compared with the placebo arm (94.0 +/- 28.3%) (P=0.36). Other capecitabine associated adverse events, including diarrhea, mucositis, and myelosuppression were not significantly different in both the arms. Conclusions: Topical diclofenac is effective in preventing all grades of HFS in patients receiving capecitabine. Diclofenac application was also associated with lesser dose reductions of capecitabine. This trial establishes topical diclofenac as the new standard of care to prevent capecitabine associated HFS. Clinical trial information: CTRI/2021/01/030592 . [Table: see text]
Purpose: Patients with Germ cell tumours (GCT) are at risk of long-term toxicities due to multimodality therapy. It is debatable whether there is an impact on the quality of life(QoL) of GCT survivors.Methods: A case-control study was conducted at a tertiary care centre in India, using the EORTC QLQ C30 questionnaire, to compare the QoL between GCT survivors(disease free> 2 years) and healthy matched controls. A multivariate regression model was used to identify factors affecting QoL.Results: A total of 55 cases and 100 controls were recruited. Cases had a median age of 32 years (interquartile range, IQR 28-40 years), ECOG PS of 0-1(75%), advanced stage III (58%), chemotherapy (94%) and 66% were >5 years from diagnosis. The median age of controls: 35 years (IQR 28-43 years).
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