ANN-LII CHENGYAO-CHANG CHENKUN-HUEI YEHChuang S.-E.Chen B.-R.DING-SHINN CHEN2021-01-282021-01-2819960008-543Xhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-0030039458&doi=10.1002%2f%28SICI%291097-0142%2819960301%2977%3a5%3c872%3a%3aAID-CNCR10%3e3.0.CO%3b2-0&partnerID=40&md5=7f3d5d9fe36b107b8a34eb6dce6539f6https://scholars.lib.ntu.edu.tw/handle/123456789/543579BACKGROUND. Hepatocellular carcinoma (HCC) is a chemoresistant tumor that frequently expresses a high level of p 170 glycoprotein of the multidrug- resistance (MDR) gene. Preliminary data suggested that VP-16 showed modest activity in HCC. Recently, schedule-dependent cytotoxicity of VP-16 has been demonstrated. In this study, we tested the therapeutic efficacy of chronic oral VP-16 plus tamoxifen, a potential MDR-reversing agent, in patients with far-advanced HCC. METHODS. A prospective single-arm study was conducted in the National Taiwan University Hospital. To be eligible, patients must have had unresectable and non-embolizable HCC, objectively measurable tumors, adequate hemogram with absolute granulocyte count greater than or equal to 2,000/mm1, and platelet count greater than or equal to 1 x 105/mm9, total serum bilirubin less than or equal to 3.0mg/dl, age less than or equal to 75 years, and a Karnofsky performance status of greater than or equal to 50%. The treatment included VP-16 (Bristol-Myers-Squibb, Princeton, NJ), 50 mg/m2/day, orally, days 1 to 21, and tamoxifen (Pharmachemie B.V., Haarlem, Netherlands), 40 mg/day, orally, Days 1 to 2); repeated every 5 weeks. RESULTS. Between December 1990 and December 1993, a total of 33 patients were enrolled in the study. There were 28 men and 5 women, with a median age of 51 years. They received an average of 3.2 (range: 1-10) courses of chemotherapy. ECOG (Eastern Cooperative Oncology Group) Grade 3 and Grade 4 leucopenia developed in 6 patients (18.2%) and 4 (12.1%) patients, respectively. Grade 3 and 4 thrombocytopenia developed in 2 patients (6.1%). Treatment-related death occurred in one patient due to sepsis. Mild gastrointestinal toxicities were common with Grade 1 and 2 nausea, Grade 1 and 2 vomiting, Grade 1 and 2 diarrhea, and Grade 1 and 2 stomatitis, developed in 13 (39.4%), 7 (21.2%), 12 (36.4%), and 16 (48.5%) patients, respectively. Grade 3 and 4 gastrointestinal toxicities were rare. Deep vein thrombosis occurred in one patient (3.0%). Eight patients (24.2%, 95%, confidence interval 11%-42%) had achieved a partial remission, with a median time-to-progression of 6 months (2-11). Median survivals of the responders and non-responders were 8.0 and 3.0 months, respectively (P < 0.05). The median Karnofsky performance status of the responders improved from 70% to 80%. CONCLUSIONS: Chronic oral VP-16 and tamoxifen had modest activity and acceptable toxicity in far-advanced HCC, and is a useful palliative treatment in about a quarter of such patients.[SDGs]SDG3etoposide; tamoxifen; adult; article; cancer combination chemotherapy; cancer staging; clinical article; clinical trial; deep vein thrombosis; drug efficacy; female; gastrointestinal toxicity; human; leukopenia; liver cell carcinoma; male; multidrug resistance; oral drug administration; priority journal; sepsis; thrombocytopenia; treatment planning; Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Drug Administration Schedule; Etoposide; Female; Humans; Liver Neoplasms; Male; Middle Aged; Prospective Studies; Tamoxifenjournal article10.1002/(SICI)1097-0142(19960301)77:5<87286084772-s2.0-0030039458