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Regorafenib for Advanced Hepatocellular Cancer
Regorafenib is an orally active inhibitor of a variety of kinases implicated in angiogenic and tumor growth-promoting pathways. A benefit for second-line regorafenib was suggested in the phase III RESORCE trial, in which 573 patients with advanced hepatocellular cancer (HCC) and radiologic progression after first-line sorafenib were randomly assigned to regorafenib or placebo. In a preliminary report presented at the 18th World Congress on Gastrointestinal Cancer, regorafenib was associated with a significant prolongation in median overall survival (10.6 versus 7.8 months) and significantly higher rates of objective antitumor response and disease control. Grade 3 or 4 adverse events occurring more often with regorafenib were hypertension, hand-foot skin reaction, fatigue, and diarrhea; 68 percent of patients required regorafenib dose modification for adverse events. While these data are preliminary, and optimal patient selection has not been established, a trial of regorafenib is a reasonable option for patients progressing after first-line sorafenib who maintain a good performance status and adequate liver function, and who are willing to trade treatment-related morbidity for the possibility of a small gain in overall survival.
Screening for Bleomycin-Induced Lung Disease
There has been no consensus as to the utility of serial pulmonary function tests (PFTs, including the diffusing capacity for carbon monoxide [DLCO]) to detect early signs of bleomycin-induced lung disease, and practice is variable. Data reported from the contemporary Danish Testicular Cancer database suggest that a systematic approach to assessing PFTs before and during therapy, with early discontinuation of bleomycin for those with a drop in the DLCO of 25 percent or more, resulted in very low rates of both acute and chronic lung disease, and no adverse effect on oncologic outcomes. We suggest assessment of PFTs, including DLCO, at baseline prior to treatment and at intervals during therapy for most adults receiving a bleomycin-containing chemotherapy regimen for any malignancy. The optimal frequency of testing is not established. We suggest discontinuation of bleomycin if there is a decrease in the DLCO of 25 percent or more, even if asymptomatic.
Menopausal Hormone Therapy in Ovarian Cancer Survivors
Menopausal hormone therapy (HT) is generally considered safe in survivors of epithelial ovarian cancer (EOC), but data are limited. A meta-analysis of six comparative studies (including two randomized trials) of women with EOC found that those treated with menopausal HT compared with no HT had no difference in EOC recurrence. They also found lower rates of cancer death in the women who were treated with HT, but this might reflect underlying better health status among women in the nonrandomized studies who were prescribed HT treatment. HT does not appear to increase the risk of epithelial ovarian cancer recurrence or mortality.
Chemotherapy for Metastatic Nasopharyngeal Carcinoma
Platinum-containing doublet chemotherapy regimens have been considered standard first-line approach to systemic therapy for metastatic nasopharyngeal carcinoma. However, specific chemotherapy combinations have not previously been compared in randomized trials, and there has not been a preferred regimen. In a phase III trial presented at the 2016 American Society of Clinical Oncology (ASCO) meeting, patients were randomly assigned to gemcitabine plus cisplatin or fluorouracil plus cisplatin. Progression-free survival was longer with the gemcitabine regimen, and a preliminary analysis suggested that it was also associated with prolonged overall survival. Based upon these results, gemcitabine plus cisplatin combination is the preferred regimen for patients with metastatic nasopharyngeal cancer.
MC1R Gene Variants and Risk of Melanoma
Variants of the melanocortin-1 receptor (MC1R) gene, a key regulator of skin pigmentation, are associated with the sunlight-sensitive red hair/fair skin phenotype, a known risk factor for melanoma. However, some MC1R variants may carry an increased risk of melanoma independent of phenotypic characteristics and sun exposure. In a case-control study including 991 patients with melanoma and 800 controls, carriers of two or more MC1R variants had an approximately twofold increased risk of melanoma, compared with wild type carriers, after adjusting for age, sex, number of sunburns before age 20, and signs of actinic skin damage. Additional studies are needed to determine the precise role of altered MC1R variants in melanoma tumorigenesis.