HEPATIC ARTERIAL INFUSION OF FLOXURIDINE, LEUCOVORIN, DOXORUBICIN, AND CISPLATIN FOR HEPATOCELLULAR-CARCINOMA - EFFECTS OF HEPATITIS-B AND HEPATITIS-C VIRAL-INFECTION ON DRUG TOXICITY AND PATIENT SURVIVAL

被引:67
作者
PATT, YZ
CHARNSANGAVEJ, C
YOFFE, B
SMITH, R
LAWRENCE, D
CHUANG, V
CARRASCO, H
ROH, M
CHASE, J
FISCHER, H
JONES, D
LEVIN, B
机构
[1] UNIV TEXAS, MD ANDERSON CANC CTR, DEPT DIAGNOST RADIOL, DIV DIAGNOST IMAGING, HOUSTON, TX USA
[2] UNIV TEXAS, MD ANDERSON CANC CTR, DEPT SURG ONCOL, DIV SURG, HOUSTON, TX USA
[3] UNIV TEXAS, MD ANDERSON CANC CTR, DIV PHARM & TRANSFUS MED & LAB IMMUNOL, DIV LAB MED, HOUSTON, TX USA
[4] BAYLOR COLL MED, DIV MOLEC VIROL, HOUSTON, TX 77030 USA
[5] BAYLOR COLL MED, VET AFFAIRS MED CTR, DEPT MED, DIV GASTROENTEROL, HOUSTON, TX USA
关键词
D O I
10.1200/JCO.1994.12.6.1204
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: 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. Patients and Methods: 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. Results: 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-nonreactive patients (P = .007). (A median has not yet been reached.) Granulocytopenia (<0.1 x 103/μL), thrombocytopenia (< 25 x 103/μL), 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). Conclusion: 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.
引用
收藏
页码:1204 / 1211
页数:8
相关论文
共 54 条
  • [2] [Anonymous], 1990, Cancer, V66, P135
  • [3] BEASLEY RP, 1991, VIRAL HEPATITIS AND LIVER DISEASE, P532
  • [4] CANCER STATISTICS, 1992
    BORING, CC
    SQUIRES, TS
    TONG, T
    [J]. CA-A CANCER JOURNAL FOR CLINICIANS, 1992, 42 (01) : 19 - 38
  • [5] BOSCH FX, 1991, ADV AP BIOT, V13, P35
  • [6] BRUIX J, 1989, LANCET, V2, P1004
  • [7] CHIARAMONTE M, 1990, LANCET, V335, P301
  • [8] CHOI TK, 1984, CANCER, V53, P401, DOI 10.1002/1097-0142(19840201)53:3<401::AID-CNCR2820530306>3.0.CO
  • [9] 2-L
  • [10] ISOLATION OF A CDNA CLONE DERIVED FROM A BLOOD-BORNE NON-A, NON-B VIRAL-HEPATITIS GENOME
    CHOO, QL
    KUO, G
    WEINER, AJ
    OVERBY, LR
    BRADLEY, DW
    HOUGHTON, M
    [J]. SCIENCE, 1989, 244 (4902) : 359 - 362