5-EPIFAT trial protocol: a multi-center, randomized, placebo-controlled trial of the efficacy of pharmacotherapy for fatigue using methylphenidate, bupropion, ginseng, and amantadine in advanced cancer patients on active treatment.

BACKGROUND: Cancer-related fatigue (CRF) is still undertreated in most patients, as evidence for pharmacological treatments is limited and conflicting. Also, the efficacy of the pharmacological agents relative to each other is still unclear. Therefore, medications that may potentially contribute to improving CRF will be investigated in this head-to-head trial. Our main objective is to compare the efficacy of methylphenidate vs. bupropion vs. ginseng vs. amantadine vs. placebo in patients with advanced cancer. METHODS: The 5-EPIFAT study is a 5-arm, randomized, multi-blind, placebo-controlled, multicenter trial that will use a parallel-group design with an equal allocation ratio comparing the efficacy and safety of four medications (Methylphenidate vs. Bupropion vs. Ginseng vs. Amantadine) versus placebo for management of CRF. We will recruit 255 adult patients with advanced cancer who experience fatigue intensity ≥ 4 based on a 0-10 scale. The study period includes a 4-week intervention and a 4-week follow-up with repeated measurements over time. The primary outcome is the cancer-related fatigue level over time, which will be measured by the functional assessment of chronic illness therapy-fatigue (FACIT-F) scale. To evaluate safety, the secondary outcome is the symptomatic adverse events, which will be assessed using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events in cancer clinical trials (PRO-CTCAE). Also, a subgroup analysis based on a decision tree-based machine learning algorithm will be employed for the clinical prediction of different agents in homogeneous subgroups. DISCUSSION: The findings of the 5-EPIFAT trial could be helpful to guide clinical decision-making, personalization treatment approach, design of future trials, as well as the development of CRF management guidelines. TRIAL REGISTRATION: IRCT.ir IRCT20150302021307N6. Registered on 13 May 2023.

Determining massage dose-response to improve cancer-related symptom cluster of pain, fatigue, and sleep disturbance: A 7-arm randomized trial in palliative cancer care.

BACKGROUND: The efficacy of various massage doses in palliative cancer care settings is still debated, and no specific protocol is available. AIM: Evaluating response to various massage doses for symptom cluster of pain-fatigue-sleep. DESIGN: A 7-arm randomized-controlled trial with weekly massage for 4 weeks depending on the prescribed dose (15-, 30-, or 60-min; 2× or 3×/week) and a 4-week follow-up. The intensities of pain, fatigue, and sleep disturbance were measured using a 0-10 scale at nine-timepoint; baseline, weekly during the intervention, and the follow-up period. Then, the mean scores of the three symptoms were calculated as the symptom cluster intensity at each timepoint. IRCT.ir IRCT20150302021307N5. SETTING/PARTICIPANTS: Adults with cancer (n = 273) who reported all three symptoms at three oncology centers in Iran. RESULTS: The odds of clinical improvement (at least 30% reduction in symptom cluster intensity from baseline) increased with dose-escalation significantly [(OR = 17.37; 95% CI = 3.87-77.90 for 60-min doses); (OR = 11.71; 95% CI = 2.60-52.69, for 30-min doses); (OR = 4.36; 95% CI = 0.94-20.32, for 15-min doses)]. The effect durability was significantly shorter at 15-min doses compared to 30- and 60-min doses. The odds of improvement for doses 3×/week was not significant compared to doses 2×/week (OR = 12.27 vs OR = 8.34); however, the effect durability for doses 3×/week was significantly higher. CONCLUSIONS: The findings indicated that dose-escalation increases the efficacy of massage for the pain-fatigue-sleep symptom cluster. Although the 60-min doses were found to be more effective, the 30-min doses can be considered more practical because they are less costly and time-consuming. Our findings can be helpful to develop massage guidelines in palliative care settings. TRIAL REGISTRATION: Iranian Registry of Clinical Trials, IRCT20150302021307N5.

Association of human papillomavirus with breast cancer: a new perspective on an old debate.

Breast cancer is a common cancer in the female population. Despite remarkable progress in the treatment of this cancer, its exact etiology is still unknown. Since the first evidence of an association between breast cancer and human papillomavirus (HPV) was provided in 1992, numerous studies have explored this subject but have reached contradictory results. In this review, the authors examine the existing evidence and hypotheses regarding the pathways whereby HPV infection can reach breast cells and the mediators linking HPV oncoproteins to breast cancer pathogenesis. Furthermore, the authors discuss contradictory findings regarding the association of HPV with breast cancer. Showing the link between HPV infection and increased genomic instability, reduced apoptosis, immune system dysfunction and progression of metastasis, the reviewed findings highlight the importance of active presence or history of HPV infection as a prognostic factor for breast tumor development.

Breast cancer is a common cancer in the female population. Although the exact cause of this cancer is still unknown, it has several major risk factors including family history, hormonal problems and age. It has been suggested that various viral infections, including human papillomavirus, can increase the likelihood of developing breast cancer. This review discusses the evidence regarding the association of human papillomavirus with breast cancer.