Patt Y Z, Charnsangavej C, Yoffe B, Smith R, Lawrence D, Chuang V, Carrasco H, Roh M, Chase J, Fischer H
Department of Gastrointestinal Medical Oncology and Digestive Diseases, University of Texas M.D. Anderson Cancer Center, Houston 77030.
J Clin Oncol. 1994 Jun;12(6):1204-11. doi: 10.1200/JCO.1994.12.6.1204.
To conduct a pilot trial of hepatic arterial infusion (HAI) of floxuridine (FUDR), leucovorin, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (FLAP) in nonresectable hepatocellular cancer (HCC) confined to the liver and assess the effects of hepatitis B (HBV) and hepatitis C (HCV) viral markers on toxicity, response to treatment, and patient survival.
Of 31 HCC patients, 13 were HBV- and HCV-nonreactive, and 18 had evidence of either current or prior HBV and/or HCV infection. Treatment was delivered through percutaneous hepatic arterial catheters, and Infusaid pumps (Shiley Infusaid, Norwood, MA) were placed in responding patients. Cisplatin (100 mg/m2) and Adriamycin (30 to 35 mg/m2) were administered on day 1, followed by a continuous 24-hour HAI of an admixture of floxuridine (60 mg/m2) and leucovorin (15 mg/m2) daily for 4 days. Treatment was repeated every 5 weeks.
Twelve (41%) of 29 assessable patients had a partial response (PR), with a median time to disease progression of 13 months. Six (50%) of 12 HBV-negative (HBV-)/HCV-negative (HCV-) and six of 17 (35%) HBV-positive (HCV+) and/or HCV-positive (HCV+) patients achieved a PR. Eight patients have been maintained in remission for a median duration greater than 15.5 months. The median survival duration of all 31 patients was 15 months, 7.5 months among HBV+ and/or HCV+ patients, and significantly longer among hepatitis-non-reactive patients (P = .007). (A median has not yet been reached.) Granulocylopenia (< 0.1 x 10(3)/microL), thrombocytopenia (< 25 x 10(3)/microL), and hospitalizations for infectious complications were significantly more common among HBV-HCV-reactive than -nonreactive patients: 56%, 50%, and 67% versus 15%, 15%, and 8%, respectively (P < .05 for all).
HAI of FLAP has induced long-term PR and has palliated extensive nonresectable HCC. Positive hepatitis serology appeared to increase bone marrow susceptibility to myelotoxic drugs. Conceivably, one or both viruses may have a direct inhibitory effect on bone marrow progenitors and thereby contribute to the observed myelotoxicity.
对局限于肝脏的不可切除肝细胞癌（HCC）患者进行氟尿苷（FUDR）、亚叶酸、阿霉素（多柔比星；阿德里亚实验室，俄亥俄州哥伦布市）和顺铂（FLAP）肝动脉灌注（HAI）的初步试验，并评估乙肝（HBV）和丙肝（HCV）病毒标志物对毒性、治疗反应和患者生存的影响。
31例HCC患者中，13例HBV和HCV均无反应，18例有当前或既往HBV和/或HCV感染的证据。通过经皮肝动脉导管进行治疗，对有反应的患者植入Infusaid泵（施利Infusaid，马萨诸塞州诺伍德）。第1天给予顺铂（100mg/m²）和阿霉素（30至35mg/m²），随后连续24小时肝动脉灌注氟尿苷（60mg/m²）和亚叶酸（15mg/m²）的混合液，每日1次，共4天。每5周重复治疗。
29例可评估患者中有12例（41%）部分缓解（PR），疾病进展的中位时间为13个月。12例HBV阴性（HBV-）/HCV阴性（HCV-）患者中有6例（50%）以及17例HBV阳性（HBV+）和/或HCV阳性（HCV+）患者中有6例（35%）达到PR。8例患者维持缓解状态，中位持续时间超过15.5个月。31例患者的中位生存时间为1个月，HBV+和/或HCV+患者为7.5个月，在无肝炎反应的患者中显著更长（P = 0.007）。（尚未达到中位值。）粒细胞减少（<0.1×10³/μL）、血小板减少（<25×10³/μL）以及因感染并发症住院在HBV-HCV反应性患者中比无反应性患者更常见：分别为56%、50%和67%，而无反应性患者分别为15%、15%和8%（所有P < 0.05）。
FLAP肝动脉灌注诱导了长期PR并缓解了广泛的不可切除HCC。肝炎血清学阳性似乎增加了骨髓对骨髓毒性药物的易感性。可以想象，一种或两种病毒可能对骨髓祖细胞有直接抑制作用，从而导致观察到的骨髓毒性。
