title: Phase I clinical trial of oral furtulon and combined hepatic arterial chemoembolization and radiotherapy in unresectable primary liver cancers, including clinicopathologic study.
abstract: Surgical resection has been accepted as the only curative therapy for primary liver cancer (PLC). Unfortunately, most patients are surgically unresectable when they seek treatment. An alternative therapeutic approach for some of these patients is transcatheter arterial chemoembolization. However, this is not curative by itself, and additional therapy is required to eradicate residual disease. This study investigates the approach of preoperative hepatic arterial chemoembolization followed by the combination of oral Furtulon (5'-deoxy-5-fluorouridine) as a radiosensitizer and external beam radiotherapy (RT). From July 1997 to December 1998, 25 patients with unresectable PLC were treated with hepatic arterial chemoembolization followed by limited-field radiotherapy plus oral Furtulon as a radiosensitizer. Hepatic arterial chemoembolization was performed with 5-fluorouracil 1 g, cisplatin 80 mg (DDP), mitomycin C (MMC) 10 mg, and arterial embolization with iodized oil-10 ml mixed with 10 mg MMC. Hepatic arterial chemoembolization was performed at regular intervals of 6 weeks, and the patients then received limited-field RT. Mean tumor dose was 4,600 cGy (range, 4,100-5,200 cGy) in daily 1.8-Gy fractions, 5 times a week. The toxicity and responses between RT and surgery were assessed. After surgical evaluation, resection was performed. The histopathologic study was also performed in the specimens of both normal and radiation-injured liver tissues from the patients who underwent resection. Seventeen of 25 patients (68%) showed an objective response. One patient with cholangiocarcinoma involving the portal lymph nodes attained a complete response. Eight patients (32%) underwent sequential resection. The most common toxicity was an increase in liver enzymes, which were less than twofold of the upper limit of normal. Follow-up computed tomography studies after treatment showed a low-attenuation area adjacent to the hepatic tumor in the target volume. On pathologic evaluation, the low-attenuation area revealed hyperemia, distended hepatic sinusoids packed with erythrocytes, and hepatic cell loss when examined with microscopy; "new-born" hepatocytes, hepatic cords in the process of forming, and endothelial cells have appeared on electronic microscopic examination. The combination of hepatic arterial chemoembolization and external radiotherapy is efficacious and a safe modality for unresectable primary liver cancers. Furtulon offers the potential for use as a clinical radiosensitizer. Radiation can significantly damage the liver tissue between 41 Gy and 52 Gy, but the new hepatocytes were forming within the radiation-injured liver after RT.
authors.affiliation: Department of Radiation Oncology, Liver Cancer Institute, Zhongshan Hospital, Shanghai Medical University, PR China.
authors.forename: Z C
authors.initials: ZC
authors.lastname: Zeng
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Tang
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Wu
authors.forename: Z C
authors.initials: ZC
authors.lastname: Ma
authors.forename: J
authors.initials: J
authors.lastname: Fan
authors.forename: L X
authors.initials: LX
authors.lastname: Qin
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.forename: J H
authors.initials: JH
authors.lastname: Wang
authors.forename: B L
authors.initials: BL
authors.lastname: Wang
authors.forename: C S
authors.initials: CS
authors.lastname: Zhong
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D016461:Chemoembolization, Therapeutic; D003131:Combined Modality Therapy; D005260:Female; D005467:Floxuridine / Q000627:therapeutic use*; D006499:Hepatic Artery; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*
chemical_list: D000964:Antimetabolites, Antineoplastic; D011838:Radiation-Sensitizing Agents; D005467:Floxuridine; C025034:doxifluridine