Combination therapy consisting of arterial infusion chemotherapy (EPF, EAP) and transcatheter arterial embolization (TAE).

From January 1988 to January 1993, 45 patients with unresectable advanced hepatocellular carcinoma (HCC) were treated with a new combination therapy consisting of arterial infusion chemotherapy and TAE. The combination therapy was performed according to our treatment schedule as follows: two courses of arterial infusion chemotherapy were given first, and then transcatheter arterial embolization (TAE) using a mixture of Lipiodol and cisplatin powder was performed. Two arterial infusion chemotherapeutic regimens were employed: EPF (etoposide, cisplatin, and 5-fluorouracil) and EAP (etoposide, Adriamycin or Epi-adriamycin, and cisplatin). The anticancer drugs were infused through a catheter inserted into the proper or common hepatic artery. Assessment was made of the anticancer effect and survival rate of each treatment method. The response to each therapy was evaluated on the basis of CT performed prior to and after the treatment. In the EPF.TAE group, the response rate was about 46%, whereas in the EAP.TAE group it was 48%. Overall, 21 of 45 patients attained a regression rate of 50% or more. Furthermore, daughter nodules decreased in size or disappeared in about 67% of 15 patients. Additionally, tumor thrombi tended to show a similar response. In all of the cases, the average duration of survival was 30.3 months, and the 1-year survival value was 68%, the 2-year survival value was 44%, and the 3-year survival value was 35%. These results were superior to those obtained with TAE therapy alone.

[A case with hepatocellular carcinoma effectively treated by continuous hepatic arterial infusion of etoposide, epirubicin and CDDP].

A 53-year-old man who suffered from advanced hepatocellular carcinoma (HCC) was treated with hepatic arterial infusion (HAI) of Etoposide, Epirubicin and CDDP. Treatment consisted of a continuous HAI of Epirubicin (50 mg/body, day 1.7), CDDP (75 mg/body, day 2.8) and Etoposide (80 mg/body, day 4-6). He had two series of infusions and was treated by transarterial embolization using CDDP powder (100 mg) added to lipiodol and aluminum stearate as suspension following HAI. The tumor regression rate was about 60% after HAI, but the remaining tumor seemed to be almost necrotic. AFP and PIVKA-II reached the normal range after TAE. We could not find lipiodol accumulated in tumor on CT carried out eight weeks after TAE. No recurrence has been noticed in the following 8 months. Toxicity was not so severe and was well tolerated.

[Hepatocellular carcinoma treated by continuous hepatic arterial infusion of etoposide, CDDP and 5-FU].

Fifteen patients with advanced hepatocellular carcinoma were treated by hepatic arterial infusion (HAI). Treatment consisted of a 24-hour continuous HAI of etoposide (60 mg/day, day 1-5), CDDP (30 mg/day, day 1-5) and 5-fluorouracil (250 mg/day, day 1-26). Three patients had two series of infusions. Five patients were treated by transcatheter arterial embolization following HAI. Among 13 evaluable patients, one showed a complete remission and five patients had a partial response. We obtained a response rate of 46.2%. Toxicity included hematologic toxicity, alopecia, nausea and vomiting. The major toxicity was myelosuppression, but it was well tolerated. These results indicate that continuous HAI of etoposide, CDDP and 5-FU is effective for advanced hepatocellular carcinoma.

[A case of hepatocellular carcinoma effectively treated by intraarterial infusion of CDDP and other agents].

It is very common for intraarterial infusion therapy of some anticancer agent to be effective against hepatocellular carcinoma. In this case, the patient was a 74-year-old man who suffered from very advanced hepatocellular carcinoma with tumor thrombus of the intrahepatic portal vein and IVC. He was treated with intraarterial infusion of CDDP, Etoposide, 5-FU, through a catheter placed in the proper hepatic artery. CDDP (30 mg/day) and Etoposide (60 mg/day) were given once every 5 days, and then 5-FU(250 mg/day) was infused daily for 26 days. The patient underwent this protocol study twice in 3 months. After the intraarterial infusion, transarterial embolization using CDDP (100 mg) powder added to lipiodol and aluminum stearate as suspension was done a month later. The tumor regression rate was 84% after intraarterial infusion of CDDP, Etoposide and 5-FU. The tumor thrombus in the intrahepatic portal vein and IVC had completely disappeared. We could not find lipiodol accumulated in the tumor after TAE. Thus, we assumed that the remaining tumor was a necrotic scar and that a complete response was obtained in the patient. There were some side effects, such as nausea, vomiting, pancytopenia and gastritis but no severe complication occurred.

[MR-angiography with intravenous administration of Gd-DTPA].

We carried out phase contrast MR-angiography of the lower extremities with intravenous administration of Gd-DTPA. Five healthy male volunteers, 25 to 40 years of age, were examined with a 0.5T MRI unit. We used fast scen (gradient echo) technique and it took about 8 minutes for whole procedure. Images were obtained before and after intravenous injection of Gd-DTPA. Injection dose was 0.1 mmol/kg. In two cases, we got images with variable flip angles. However angles of 30 or 40 degrees were thought to be best on the scan with Gd-DTPA. In three cases, we repeated short time procedures for about 4 minutes each time and continued to check the signal intensities of vessels for as long as one hour. The signal intensities greatly increased soon after administration of Gd-DTPA, and then they gradually decreased, but for as long as 60 minutes after administration they remained much higher than those before administration of Gd-DTPA. MR-angiography with Gd-DTPA was found very useful to demonstrate the peripheral femoral vessels clearly. No significant side effect was noticed in any case. Therefore, this method was thought to be very useful clinically.

[New technique of intra-arterial catheterization via the branch of left axillary artery for continuous infusion chemotherapy].

A new technique of intra-arterial catheterization via the branch of left axillary artery is described. This provides relatively swift and safe insertion and long-term placement of an infusion catheter through the left thoracoacrominal artery without exposure of the left axillary artery, that was required by conventional methods. With our technique, the tip of the catheter tends to enter the distal axillary artery because of oblique angulation of the trunk of the thoracoacrominal artery. Therefore, the tip of the catheter in the axillary artery must be deflected using a deflecting guidewire, so that it will advance into the subclavian artery and then down to the descending aorta. The deflection guidewire can also be of help when the catheter tip migrates into either celiac or SMA. The selective catheterization has been successful in all twenty seven patients without preliminary selective left subclavian arteriography.

[Chemoembolization therapy of hepatocellular carcinoma-antitumor effect and side effect].

Chemoembolization therapy with arterial injection of a mixture of various anticancer agents (CDDP, ADR, MMC) and Lipiodol along with gelfoam particles was carried out on 158 cases of hepatocellular carcinoma between January 1985 and July 1987. In two groups using CDDP the tumor regressed 50% or more in higher percentage than in the groups without CDDP. The antitumor effect was more significant in the group using CDDP and ADR than in the group using CDDP alone. No significant side effect was noted in any case.

[Chemoembolization therapy with cisplatin.lipiodol (CDDP.lipiodol) in primary liver cancer--with special reference to hepatocellular carcinoma].

From Jan., 1985 to Mar., 1986 thirty-six patients with primary liver cancer received transcatheter arterial chemoembolization therapy with Cisplatin (100 mg) blended into Lipiodol (5 ml) and simple embolization therapy with Gelfoam particles. Thirty-three cases out of 36 had hepatocellular carcinoma, one had hepatoblastoma and one had adenocarcinoma. Ten (31%) out of 32 had hepatocellular carcinoma, and showed objective tumor reduction greater than 50% (partial response) regarding the main tumor. Of the 33 there was one sudden death due to intracerebral hemorrhage. Only two out of 25 cases with daughter nodules showed slight reduction. Almost all cases with daughter nodules showed no response to chemoembolization therapy. Five patients died after chemoembolization therapy during the fifteen-month study period. Two patients died of liver abscess or cholecystitis and surrounding abscess, one died of intracerebral hemorrhage, one died of hepatic failure and the remaining case was one of tumor death.