A case of liver and lung metastases of rectal cancer responding well to 5-FU hepato-arterial infusion (HAI) with combined use of oral UFT

We have studied the pharmacokinetics of 5-FU hepato-arterial infusion (HAI) with combined use of oral UFT for colorectal cancer cases previously. The plasma 5-FU concentration in cases of 5-FU HAI plus UFT is 1.5-6 times as high as with 5-FU HAI only. We report a rectal cancer case with liver and lung metastases treated successfully with this protocol. A 75-year-male underwent low anterior resection for rectal cancer as Rab, 3.5 x 3 cm, well, ai, n2, P0, H3, M1 on March 26, 2002. For synchronous hepatic and lung metastases, he received weekly 5-FU 1,000 mg HAI, UFT 4T 2 x postoperatively. As a result, liver and lung metastases disappeared over 6 months. We recommend weekly 5-FU HAI with combined use of UFT, which can be more effective not only for liver metastases but also for extra-hepatic lesion of colorectal cancer.     

The 5-fluorouracil hepato-arterial infusion with oral UFT therapy for the hepatic and extra hepatic metastases of colorectal cancer

BACKGROUND: The 5 fluorouracil hepato-arterial infusion (5-FU HAI) therapy has a good effect on the liver metastases of colorectal cancer. To gain the antitumor effect of the extra-hepatic lesion, an oral UFT was combined with 5-FU HAI (pharmacokinetic modulating chemotherapy, PMC) to enhance the plasma 5-FU concentration. METHODS: UFT (200-400 mg/day) was orally administered daily and a continuous infusion of 5-FU (1,000-1,500 mg/5 h) was given once a week. Eight patients were treated with this regimen. Five of the eight have extra-hepatic lesions with liver metastases when this treatment was started. The response, time to progression, survival, and toxicity were detected. RESULTS: Four of the five patients with extra-hepatic lesion were evaluated. The response rate was 50% (1 CR, 1 PR, and 2 SD). For the liver metastases, the response rate was 62.5% (1 CR, 4 PR, 2 SD, and 1 PD). Grade 2 leukopenia was found in 1 patient. CONCLUSIONS: The 5-FU HAI with an oral UFT therapy had a good effect on the extra-hepatic lesions as well as hepatic metastases of colorectal cancer.     

Two case reports of complete regression of liver metastases from colorectal cancer after locoregional immunochemotherapy

Hepatic arterial infusion (HAI) with pharmacokinetic modulating chemotherapy (PMC) has been well known to be one of the most effective protocols for unresectable liver metastases from colorectal cancer. PMC is a combination of oral UFT and continuous hepatic arterial 5-FU infusion. We present herein the cases of two patients with multiple liver metastases from colorectal cancer in whom complete regression (CR) was achieved by HAI with PMC in combination with Lentinan (immunostimulator). These patients received HAI via an implantable port system with a 4-24-hour continuous perfusion of 5-FU at 1,000 mg/m2 plus Lentinan at 2 mg/body once a week, and oral administration of UFT at 200-300 mg/m2/day everyday. CR of all metastatic lesions in the liver was achieved 4 months after the initiation of the treatment in both patients. One patient maintained CR for 3 months, but he died due to a recurrence of liver metastases and peritoneal dissemination 19 months after the initiation of the treatment. The other patient has been well without recurrence for 21 months. Because the liver is the largest immunologic organ, Lentinan could have activated lymphocytes and macrophages in the liver. Judging from the clinical experience of these two cases, HAI with PMC in combination with Lentinan could be one of the most promising treatment strategies for unresectable liver metastases from colorectal cancer.     

A case of colon cancer with multiple liver, lung and bone metastases successfully treated with combined weekly high-dose 5-FU (WHF) chemotherapy with UFT and CPT-11

A 54-year-old woman who had ascending colon cancer with multiple liver and lung metastases underwent rt. hemicolectomy and catheter insertion into the gastroduodenal artery for arterial infusion chemotherapy. On postoperative day 7, she had nausea and vomiting due to the enlarged multiple liver metastases on lateral segment. Intraarterial infusion of 5-FU 1,000 mg/m(2) for 5 hours weekly (WHF: weekly high-dose 5-FU) was started at first. After 3 courses, her symptoms improved, oral intake could be started, and liver metastases showed significant reduction on abdominal CT. Three months after surgery, bone scinti revealed multiple bone metastases. Combined HAI (5-FU: 600 mg/m(2)/3 hr) chemotherapy with UFT (400 mg/body) + CPT-11(80/body) and UFT (400 mg/body)/LV (75 mg/body) + CPT-11(100 mg/body) were effective for highly advanced colon cancer in terms of QOL. Eight months after surgery, she was doing well and the chemotherapy was continued. WHF therapy was effective for digestive symptoms due to liver metastasis.     

Hepatic arterial infusion of low-dose leucovorin/5-FU chemotherapy for unresectable hepatic metastases from colorectal cancer

Hepatic arterial infusion (HAI) chemotherapy for unresectable liver metastases from colorectal cancer (CRC) is generally indicated to patients without extrahepatic lesions. This study was performed to examine whether or not it was possible to obtain a comparable survival time, response rate (RR) and modest toxicity combining low-dose LV and 5-FU (LV/5-FU) with HAI for the patients with unresectable liver metastases from CRC. Twenty two patients with unresectable multiple liver metastases were enrolled in the study. These were patients who had been admitted from 1994 to 2003 in our hospital. Patients were given LV at 25 mg/body immediately followed by 5-FU at 500 mg/body as a 2-hour HAI daily for 5 consecutive days every 5 weeks. The median survival time (MST) of HAI patients was 24.5 months. According to the treatment in the HAI patients, one patient was CR, 6 were PR, 9 were NC, 6 were PD, and the response rate (RR) was 31.8% (7 of 22 patients). The toxicities to this regimen on HAI were observed in 12 patients, and grades 3 or 4 were in 3 patients only. These results suggested that HAI with LV/5-FU can be useful for unresectable liver metastases from CRC.     

Results of pharmacokinetic modulating chemotherapy in combination with hepatic arterial 5-fluorouracil infusion and oral UFT after resection of hepatic colorectal metastases

BACKGROUND: Pharmacokinetic modulating chemotherapy (PMC) is a new therapeutic concept in combination with continuous 5-fluorouracil (5-FU) infusion and UFT. UFT enhanced plasma 5-FU concentration and antitumor effects during 5-FU infusion. The authors report on their experiences with arterial 5-FU infusion and UFT after resection of hepatic colorectal secondaries. METHODS: Fifty-eight patients were divided into two groups after hepatectomy. Group A, 30 patients, underwent hepatic arterial infusion (HAI) via implantable port system with perfusion 5-FU for 2 consecutive days per week at 600 mg/m(2)/day, and oral administration of UFT at 400 mg/day for 5-7 days per week, repeated 10 times, and Group B, 28 patients, underwent oral administration of UFT at 400 mg/day for 6 months. All the patients were managed at the outpatient clinic at Hyogo College of Medicine, and recurrence, survival, and toxicity were documented. Plasma 5-FU concentrations during chemotherapy were detected using high performance liquid chromatography. RESULTS: Maximum plasma concentrations of 5-FU in Group A reached 144.0 ng/mL and in Group B 58.7 ng/mL. Cumulative 5-year survival rate after hepatectomy in Group A was 59% and in Group B was 27%. (P = 0.00001) HAI-PMC drastically decreased hepatic recurrence (median hepatic recurrence free times were 34.2 months in Group A vs. 18.4 months in Group B; P = 0.00002). Grade 3 toxicity in Group A was found in 3 patients CONCLUSIONS: Pharmacokinetic modulating chemotherapy was designed as a uracil-related biochemical modulation. HAI-PMC significantly decreased hepatic recurrence after curative resection. This new chemotherapy concept significantly improved prognosis in patients with hepatic colorectal metastases.     

A case report--combination chemotherapy with oral UFT and CPT-11, 5-FU, l-LV by hepatic arterial infusion for multiple hepatic metastasis from sigmoid colon cancer

A 64-year-old woman was diagnosed with multiple hepatic metastases from sigmoid colon cancer. She underwent resection of the colon and catheter insertion into the hepatic artery for arterial infusion in August 2006. She was then treated with postoperative combination chemotherapy consisting of UFT and CPT-11, 5-FU, l-LV. UFT was administered orally at 400 mg/body/day every day and CPT-11 was injected at 100 mg/body/week, 5-FU at 750 mg/body/week, and l-LV at 300 mg/body/week for 8 continuous weeks. After 2 months of the chemotherapy, the metastatic liver tumors disappeared. So hepatic arterial infusion with the same regimens was injected once every month 4 more times. Oral UFT was administered every day. After 6 months of the combined chemotherapy above, we judged the effects of the chemotherapy to be a complete response. Then the chemotherapy was followed by oral UFT only. As severe nausea and vomiting were seen in this patient with an initial dose of 150 mg/body/week of CPT-11 at first, we reduced the dose of CPT-11 to 100 mg/body/week. From then, outpatient care was possible because no severe events were observed. Combined chemotherapy consisting of oral UFT and CPT-11, 5-FU and l-LV by hepatic arterial infusion is suggested to be a new and effective treatment for multiple liver metastases from colorectal cancer.     

Results of hepatic arterial infusion chemotherapy with 5-FU and leucovorin for unresectable liver metastases from colorectal cancer

PURPOSE: Hepaticarterial infusional(HAI)5-FU chemotherapy, which involves the use of interventional radiology technique, has matured technically in Japan in the 1990's. The antitumor effect of 5-FU is enhanced by combination with leucovorin. This study was performed to evaluate the efficacy and toxicity of HAI 5-FU and leucovorin chemotherapy for patients with unresectable liver metastases from colorectal cancer. METHODS: Treatment was given to 20 patients with unresectable liver metastases from colorectal cancer. The chemotherapy regimen consisted of weekly HAI of 5-FU(1,000 mg/body)and leucovorin(250 mg/body)over five hours. The survival and response rates to the therapy were assessed according to RECIST. Hematologic and non-hematologic toxicity was assessed according to CTCAE v3.0. RESULTS: Combined HAI 5-FU and leucovorin therapy was carried out an average of 27 times. The response rate for liver tumors was 75%, and the median survival time was 22 months. The applied regimen caused only mild adverse events. There was no evidence of myelosuppression except for platelet decrease(grade 3)in a patient with chronic renal failure. CONCLUSION: This HAI approach using 5-FU and leucovorin was effective and the therapy for unresectable liver metastases from colorectal cancer was tolerated well. Therefore the HAI approach should be reconsidered as an effective therapy against this disease in Japan.     

Combination chemotherapy with hepatic arterial infusion of 5-fluorouracil (5-FU) and systemic irinotecan (CPT-11) in patients with unresectable liver metastases from colorectal cancer

PURPOSE: Hepatic arterial infusion (HAI) chemotherapy for hepatic metastasis from colorectal cancer has higher response rates compared with systemic chemotherapy, but can not control extrahepatic lesions. So the combination chemotherapy with HAI plus systemic chemotherapy is expected. This study ascertained the efficacy and toxicity of combined chemotherapy with HAI plus systemic CPT-11. METHODS: Seventeen patients were treated with concurrent HAI 5-FU 700-800 mg/m(2) on day 1, 8, 15, 22 and systemic CPT-11 70-80 mg/m(2) on day 1 and 15. Treatment was repeated every 28 days. RESULTS: The objective response rate for all patients was 76.5% (13 of 17 patients), and time to progression was about 10 months. Median survival time was about 20 months, and no difference was seen in the survival of patients without extrahepatic lesions and patients with extrahepatic lesions (21 months vs 18.5 months; p=0.5). The incidence of new extrahepatic metastasis in patients without extrahepatic lesions was 9% (1 of 11 patients). Grade 3 or 4 neutropenia was found in only 2 patients (11.8%). CONCLUSION: Combination therapy with HAI 5-FU plus systemic CPT-11 may be safely administered to patients with colorectal cancer. The incidence of new extrahepatic metastases was low in comparison with reports of HAI monotherapy.     

A clinical study of hepatic arterial infusion chemotherapy with 5-FU and leucovorin for liver metastases

We followed patients who underwent hepatic arterial infusion chemotherapy (HAI) with 5-FU and Leucovorin for liver metastases. Since CR (complete response) and PR (partial response) were achieved, this therapy seems to be effective. 5-FU metabolized on its first pass through the liver, and the hepatic extraction with rapid HAI is lower than that with slow HAI. It is suggested that control of extrahepatic lesions thought rapid HAI is useful for life prolongation.     

Concentration of 5-FU after hepatic artery infusion chemotherapy for liver metastases of colorectal cancer

AIM: Hepatic artery infusion chemotherapy (HAI) using 5-FU is a good method of treating patients with liver metastases from colorectal cancer. We investigated the toxicity and the response in relation to the concentration of 5-FU after HAI, and examined various factors that would have an effect on the 5-FU concentration. RESULTS: The mean 5-FU concentration was 480 ng/ml. The most frequent complication of HAI was anorexia. Three of 14 patients suffered from grade 2 or 1 anorexia. The 5-FU concentration of these patients was higher (1,010, 721, 642 ng/ml) than that of the others. The response rate of HAI was 36%. The 5-FU concentration of responders tended to be lower than that of non-responders. None of the following was related to the 5-FU concentration: whether or not the gallbladder was resected, whether or not co-lateral blood flow was recognized, or the volume of the patients' liver. CONCLUSION: 5-FU concentration after HAI has some effect on anti-tumor response and gastrointestinal toxicity.     

Effects of combination chemotherapy with topical application of 5-FU ointment to mice's tongue and UFT

After oral administration of UFT and lingual topical application of 5-FU ointment to normal mice, the change of the concentration of 5-FU and Uracil in the tongue, liver and blood serum were studied. We compared with UFT only group, 5-FU ointment only group and the both combination chemotherapy group. 1. As for the tongue concentrations, 5-FU levels in both combination chemotherapy group and 5-FU ointment only group were higher compared to UFT only group. There was no difference between combination chemotherapy and 5-FU ointment only group. Uracil at 21-days in combination chemotherapy group were higher than others. 2. The liver concentrations of 5-FU at 21-days was significantly higher. 3. The blood serum concentrations of 5-FU in both combination chemotherapy and 5-FU ointment only groups revealed similar results. Thereafter, combination chemotherapy in oral region with topical application of 5-FU ointment and UFT may be effective.     

Basic research supported developments of chemotherapy in nonresectable isolated colorectal liver metastases to a protocol of hepatic artery infusion using mitoxantrone, 5-FU + folinic acid and mitomycin C

OBJECTIVE: Since the developments in systemic chemotherapy of metastasized colorectal cancer have not resulted in substantial gains in survival times, we wished to improve the course of isolated nonresectable colorectal liver metastases (CPLM) by hepatic arterial infusion treatment. BACKGROUND: Patients (pts) with CRLM have a worse fate than those pts whose liver metastases could be resected. Systemic (i.v.) chemotherapy for CRLM/colorectal metastases does not improve survival to a relevant level (median survival time (med. surv.) after 5-Fluorouracil + Folinic Acid (5-FU + FA) i.v.: 6.4-14.3 months (m)). Hepatic artery infusion (HAI) with 5-Fluorode-oxyuridine (5-FUDR) has been demonstrated in a metaanalysis of randomized trials to be superior to i.v. treatment/palliative care (med. surv.: 15 vs. 10 m). The benefit of HAI with 5-FUDR, although recommended as treatment for CRLM, is severely compromised by the 5-FUDR induced hepatotoxicity, leading eventually to sclerosing cholangitis (SC)/liver scirrhosis. We have stepwise developed a protocol for HAI of CRLM, which is superior to HAI with 5-FUDR, and, most evidently, to systemic chemotherapy. PATIENTS/METHODS: Between 1982-1997, 222 CR (L) M patients were treated within subsequent protocols (Table). In protocol A, 68 CRLM pts received HAI with 5-FUDR (A1: nonrandomized pts; A2: randomized pts). In protocol B (randomized pts.), 46 pts received 5-FUDR i.a. (via HAI) + i.v. In protocol C, systemic chemotherapy with 5-FU + FA was conducted in 34 pts with metastasized colorectal cancers, including CRLM. In protocol D 5-FU + FA was delivered via HAI in 25 pts with CRLM. In protocol E, based on in vitro phase II studies and the results of protocol D, Mitoxantrone and Mitomycin C were added to 5-FU + FA (MFFM). Fifty (50) CRLM pts received HAI with MFFM. RESULTS: The response rates, med. surv. times, systemic toxicity and SC rates are shown in the table. HAI with MFFM produced objective responses in 66%, the med. surv. was 27.4 m, and no SC occurred. The ports surgically placed for HAI, e.g., in protocols D and E, functioned in 90%, 82%, and 76% 6, 9, and 11 m after start of the HAI. Quality of life in protocol E was high. Nine pts from protocols D + E with either partial (PR, 7 pts) or complete (CR, 2 pts) remissions received a secondary liver resection without hospital mortality, and 7/9 pts are living 2-58 m after liver resection, 2/9 pts died 11 and 22 m after resection. [table: see text] SUMMARY/CONCLUSIONS: Our learning curve to achieve optimal treatment of CRLM resulted in a protocol using HAI with MFFM. The results of this protocol (E) including the high remission rate, long median survival time, good port function, high quality of life, and, most interestingly, the possibility to downstage and resect primarily nonresectable metastases, seem to be superior to HAI with 5-FUDR of 5-FU + FA and to systemic chemotherapy with 5-FU + FA. This hypothesis is currently examined in a phase III study (HAI with MFFM vs. 5-FU + FA i.v.).     

Evaluation of the non-effective cases of irresectable multiple liver metastasis of colorectal cancer receiving hepatic arterial infusion chemotherapy

PURPOSE: Hepatic arterial infusion (HAI) chemotherapy is one of the suitable therapies for irresectable multiple liver metastasis from colorectal cancer, but in nearly half of such cases the therapy does not prove effective. Our goal is to clarify the characteristics of non-effective cases. METHODS: 84 cases with irresectable multiple liver metastasis from colorectal cancer were investigated clinicopathologically, and were divided into two groups; non-effective cases (N = 38) and effective cases (N = 46). All cases received continuous arterial infusion chemotherapy using 5-FU according to the following regimen; 5-FU (500 mg/day) was infused in the hepatic artery over 7 or 10 days for induction, and the infusion was maintained (250 mg/day) to the hepatic artery for 7 days every other week after the induction therapy. We evaluated the efficacy of HAI chemotherapy by Computed Tomography. RESULTS: There were statistically significant differences among these two groups in histological types. Rates of the histological type of non-effective cases were well (31.6%), mod (57.9%), por (7.9%), and muc (2.6%), respectively. Those of the effective cases were well (63.0%), mod (34.8%), por (0%), and muc (2.2%), respectively. In non-effective cases, 16 out of 38 cases (42.1%) had extra-hepatic metastasis. On the other hand, only 3 out of 46 cases (6.5%) had such metastasis in effective cases. CONCLUSION: There were non-well type cancers and extra-hepatic metastasis in a large number of non-effective cases. We thought that those cases were basically high-grade malignancies, so these were the limits of HAI chemotherapy for irresectable multiple liver metastasis of colorectal cancers.     

A case of liver metastasis of pancreatic cancer that was resistant to S-1 and gemcitabine successfully treated by 5-FU and cisplatin hepatic arterial infusion

We report a case of postoperative liver metastasis of pancreatic cancer that was resistant to S-1 and gemcitabine (GEM) successfully treated by hepatic arterial infusion of 5-fluorouracil (5-FU) and cisplatin (CDDP). A 70s woman was referred to our hospital for treatment of a pancreatic head cancer in November 2007. Pancreaticoduodenectomy with a regional lymphadectomy was performed in December 2007 and the pathological stage was Stage IVa. Adjuvant chemotherapy of UFT was administered one month after operation. However, a second chemotherapy of S-1 was administered because DUPAN-2 levels showed a high range 8 months after operation. Ten months after operation, abdominal computed tomography demonstrated a 2 cm tumor in the liver. Although, we performed a systemic GEM infusion and a combination of GEM and S-1, the liver metastasis had progressed. Then, hepatic arterial infusion (HAI) chemotherapy of 5-FU/CDDP was instituted weekly. This efficacy maintained a Partial Response from the start of HAI to the fifth month. She is alive to date, maintaining a stable tumor growth of 30 months after surgery. We suggest that HAI chemotherapy of 5-FU+CDDP might be an effective treatment to liver metastasis of pancreatic cancer and prolong prognosis of those patients.     

Complete responses in patients with unresectable liver metastases from colorectal cancer with weekly high-dose 5-FU plus one-shot CDDP HAI

Thirty-two patients with unresectable liver metastases from colorectal cancer, treated by intermittent hepatic arterial infusion of high-dose 5-FU combined with CDDP, were assessed. As a result of this treatment, the overall response rate was 65.6%, and eight patients (25%) which contained three autopsy cases revealed a complete response. The mean doses of 5-FU and CDDP which was administered in the eight patients were 24.3 g and 65 mg, respectively. One of the eight patients showed complete disappearance of liver metastasis on the CT scan after arterial infusion of 4.5 g of 5-FU, and necrosis or disappearance of the tumor was present in more than 2/3 of the whole lesion. Autopsy showed focal or zonal necrosis, distorted reconstruction of architecture, and cholangiolitis of the liver which were administered more than 15 g of 5-FU. Intermittent hepatic arterial infusion of high-dose 5-FU combined with CDDP is proved to be a useful locoregional chemotherapy for liver metastasis from colorectal cancer. We should evolve new treatment modalities for extrahepatic metastases, as HAI combined with the systemic chemotherapeutic regimen.     

Phase I/II study of irinotecan, UFT and leucovorin with hepatic arterial infusion using 5-FU in colorectal cancer patients with unresectable liver metastases

Purpose

To evaluate the efficacy and tolerability of systemic chemotherapy with irinotecan (CPT-11), UFT and leucovorin (LV) combined with hepatic arterial infusion (HAI) consisting of 5-fluorouracil (5-FU) in colorectal cancer patients with unresectable liver metastases.

Methods

Patients were treated concurrently with escalating doses of intravenous CPT-11 (100, 120, and 140?mg/m²) on day 1 of each 14-day treatment cycle, with oral UFT (300?mg/m² per day) and LV (75?mg/body per day) on days 1?C7 of each cycle, and with HAI 5-FU (2,000?mg/week) on days 8?C14 of each cycle.

Results

Twelve patients were enrolled in the phase I study. The maximum-tolerated dose was not reached. Consequently, the recommended dose of CPT-11 for the phase II study was determined to be 140?mg/m². Twenty-two patients were evaluated in the phase II study. Five patients experienced grade 3 neutropenia, two experienced grade 3 anorexia, two experienced nausea, and two experienced vomiting. An overall response was observed in 19 out of 22 patients (86.4%). The median progression-free survival period was 11.2?months, and the 3-year survival rate was 50.6%. Fourteen patients (63.6%) were ultimately able to undergo a complete liver resection.

Conclusions

Chemotherapy with CPT-11 and UFT/LV combined with HAI yielded a high response rate and enabled a significant proportion of patients with initially unresectable liver metastases to undergo surgical resection. Further trials are warranted.     

Hepatic arterial infusion (HAI) chemotherapy achieved a complete response (CR) for multiple liver metastases of colorectal cancer--two case reports

We encountered two cases of concurrent multiple liver metastases of colorectal cancer in two patients who achieved a complete response (CR) to hepatic arterial infusion (HAI) chemotherapy. The first case is a 64-year old man who was found to have anemia, and a diagnosis of ascending colon cancer was made. There were 6 metastatic lesions in both lobes of the liver. A right hemicolectomy was performed. Postoperative chemotherapy consisted of 2 g of oral UFT-E as well as 3 mg of CDDP and 500 mg of 5-FU administered by HAI. The metastatic lesions disappeared after 9 courses of chemotherapy were carried out. A partial hepatectomy was performed in the scarred area. Histopathological examination revealed no cancer cells. No recurrence has been observed for 4 years and 10 months since achieving CR. The second case is a 69-year-old man who had thin stool and bloody stool. Rectal cancer was diagnosed. Five metastatic lesions were noted in both lobes of the liver. A low anterior resection was performed. l-LV 25 mg and 5-FU 500 mg were given postoperatively by HAI. After three courses of chemotherapy postoperatively, metastatic lesions disappeared. No recurrence has been noted for 2 years and 1 month since achieving CR. HAI chemotherapy is considered one of the useful treatment options for patients with multiple liver metastases of colorectal cancer.     

Oral uracil/ftorafur (UFT) plus leucovorin as first-line chemotherapy and salvage therapy with weekly high-dose 5-fluorouracil/leucovorin for the treatment of metastatic colorectal cancer

BACKGROUND: The purpose of this study was to determine the efficacy and toxicity of uracil/ftorafur (UFT) plus oral leucovorin (LV) as first-line chemotherapy for patients with metastatic colorectal cancer and salvage chemotherapy with weekly high-dose 5-fluorouracil (5-FU)/LV 24 h infusion. METHODS: Adult patients with no prior chemotherapy for metastatic diseases were enrolled to receive oral UFT 300 mg/m(2)/d plus LV 90 mg/d for 28 days. Treatment was given continuously for 28 days followed by a 7 day rest period from all treatment. For UFT failed patients, weekly 24 h infusion of 5-FU 2600 mg/m(2) plus LV 100 mg/m(2) was used as salvage therapy. RESULTS: Fifty-one patients with metastatic colorectal cancer were enrolled in the study. The objective response rate was 29.5% [95% confidence interval (CI), 16.8-45.2%] among the 44 evaluable patients and 25.5% in the intent-to-treat population. The median survival for all 51 patients was 16.6 months. The median time to progression was 5.9 months. Diarrhea was the major adverse effect of UFT/LV that made patients reduce dosage. Grade 3 or 4 diarrhea developed in 13.7% of patients. Twenty-six patients were treated with weekly 24 h infusional 5-FU/LV as salvage therapy and only two patients responded. CONCLUSION: Our results suggest that this 28 day schedule of UFT/LV regimen may offer a well-tolerated, full oral treatment option with efficacy that appears comparable to that of intravenous 5-FU/LV regimens. Parenteral 5-FU/LV as salvage therapy for UFT refractory patients is not recommended.     

Regional treatment of esophageal liver metastasis by intra-arterial low-dose 5-FU therapy

The prognosis of esophageal liver metastasis remains poor because of the high incidence of synchronous metastasis in other area and insufficient response to systemic chemotherapy. We assessed loco-regional anticancer potential of intra-arterial 5-FU chemotherapy for esophageal liver metastasis aimed at combination with systemic chemotherapy, radiotherapy and ablation therapy as a multidisciplinary treatment. Six patients of esophageal cancer with liver metastasis and without extra-hepatic metastasis were enrolled. Intra-aortic chemotherapy consisted of 5-FU (250 mg/body) in a one-shot infusion or a continuous infusion for 7 days with 2-week intervals until failure. The responses of liver metastasis were 2 cases of CR, 3 of PR and 1 of SD. The response rate and the local control rate were 83% and 100%, respectively. The maximum time to progression was 53 months. Grade 3/4 toxicity was not observed. Two cases had catheter failure and the treatment was interrupted. Liver metastases were controlled well until death in all cases except one. Low-dose intra-aortic 5-FU chemotherapy provided a good regional response and a combination with systemic chemotherapy may prolong survival for the patients of liver metastasis of esophageal cancer.