Chemoradiotherapy with low-dose cisplatin and 5-FU for advanced esophageal cancer

We evaluated the efficacy of chemoradiotherapy (CRT) for advanced esophageal cancer, from the view point of response. The relationship between chemo-radiosensitivity and dihydropyridine dehydrogenase (DPD), thymidylate synthase (TS), and p53 was investigated immunohistochemically. Thirteen patients with inoperable advanced esophageal cancer were involved in this study. CDDP of 10 mg/m2/day and 5-FU of 335 mg/m2/day were infused intravenously (day 1-5, day 15-19). Radiation was delivered concomitantly at a total dose of 30 Gy. Expressions of p53, DPD and TS were detected using immunohistology in the biopsy samples taken before CRT from 8 patients. Partial response was observed in 8 cases, no change in 4 cases, and progressive disease in one case. The overall response rate was 62%. The reduction rate was higher in tumors positive for p53 expression than in negative ones. The same was true for DPD and TS. The Treatment effect was more precisely predicted by combination of p53, DPD and TS. CRT with low-dose CDDP + 5-FU chemotherapy was effective and combination with p53, DPD, and TS might be a predictive marker for CRT in patients with advanced esophageal cancer.     

A case of gastric cancer with liver metastasis responding to low-dose CDDP/5-FU combination chemotherapy

We reported a case of a 62-year-old female with gastric cancer accompanied by liver, Virchow and paraaortic lymph nodes, and bone metastasis (taken low-dose cisplatin (CDDP)/5-fluorouracil (5-FU) combination chemotherapy). CDDP (10 mg/body/day) was injected on 1-5 days i.v. and 5-FU (500 mg/body/day) was injected i.v. continuously on 1-7 days. This treatment cycle was repeated for 4 weeks. After 4 cycles, liver metastasis disappeared without severe side effects. Primary lesion and Virchow's lymph nodes metastasis were reduced. However, bone and paraaortic lymph node metastasis showed no response. It was considered that low-dose CDDP/5-FU combination chemotherapy was effective for liver and lymph nodes metastasis of gastric cancer in this case.     

Theoretical basis for low-dose CDDP/5-FU therapy]

The theoretical basis for low-dose cisplatin (CDDP)/5-fluorouracil (5-FU) therapy is rather clear. CDDP can inhibit methionine-uptake into tumor cells and cause depletion of folate cofactors including 5-CH3FH4 and FH4, which are essential for the formation of a ternary complex with thymidylate synthetase and 5-fluorodeoxyuridine, an active metabolite of 5-FU. The literature on this mechanism are reviewed herein, and the methionine-dependency of human cancer xenografts and the modulation of 5-FU-cytotoxicity through methionine-depletion are reported.     

Treatment with 5-FU modulated by low-dose CDDP for advanced cancers and recurrent cases of metastasis

Advanced gastric, colon and esophageal cancers (n = 21) were treated with 5-FU (250 mg) modulated by CDDP (5 mg). The reductive ratio of tumor was 6/21 (28.6%). Six cases of partial response (PR) were limited with no surgical treatment and exploratory laparotomy of all cases, and the effectiveness rate was 54.5% (6/11). Few side effects, such as dysfunction of bone marrow and kidney, were noted. Even if side effects occurred, they were mild. We concluded that excellent treatment with 5-FU modulated by CDDP has markedly improved the efficacy.     

Epithelioid haemangioendothelioma of the liver: objective response to hepatic intra-arterial 5-FU

A case of an epithelioid haemangioendothelioma of the liver is presented. The tumour was unresectable at laparotomy because of extensive involvement of both lobes of the liver. The histological appearances of the biopsy taken at operation suggested that the lesion was at the more malignant end of the spectrum for these tumours. The patient was treated by cycles of hepatic intra-arterial 5-fluorouracil with relief of symptoms and prolonged survival. It is important to recognize this type of neoplasm which bears resemblance to other liver pathologies, in particular, to sclerosing cholangiocarcinoma.     

Validity of two-hour continuous hepatic arterial infusion chemotherapy with low-dose 5-FU for unresectable liver metastasis from colorectal cancer

The significance of hepatic arterial infusion chemotherapy for unresectable liver metastases from colorectal cancer was evaluated in 50 patients, who received either of the following regimens: 1 shot 5-FU + epirubicin + MMC (FAM group); hepatic arterial infusion of 5-FU for 2 hours + MMC (MF group); hepatic arterial infusion of 5-FU for 2 hours (5-FU group). There were no differences in the clinicopathological backgrounds of the patients among the groups. The mean survival time was 10.3 months, 16.0 months and 16.2 months in the FAM, MF and 5-FU groups. The effective percentages were 0%, 40% and 31% in the FAM, MF and 5-FU groups and the survival time of the effective cases was 18.1 months and 21.8 months in the MF and 5-FU groups. The MF group and 5-FU group showed significant improvement in prognosis. Concerning side effects, myelo-suppression and gastrointestinal toxicity appeared frequently in the MF group. In conclusion, 2-hour continuous hepatic arterial infusion with low-dose 5-FU for unresectable liver metastases from colorectal cancer may be helpful for improvement of prognosis.     

Preliminary clinical evaluation of low-dose cisplatin and continuous infusion of 5-FU (LFP) chemotherapy after weekly high-dose 5-FU therapy for the treatment of liver metastases from colorectal cancer

In this study, we evaluate the efficacy of low-dose cisplatin and continuous 5-FU infusion systemic chemotherapy (LFP therapy) for the treatment of unresectable and recurrent liver metastases from colorectal cancer after weekly high-dose 5-FU therapy via the hepatic artery (WHF therapy). At the start of chemotherapy, 12 patients with multiple extrahepatic lesions were treated with the LFP therapy (LFP group), and 18 patients with none or a few extrahepatic lesions were treated with the WHF therapy followed by the LFP therapy (LFP after WHF group). In the LFP group, the response rate was 50.0% (PR 6) and the one-year survival rate was 50.0%. On the contrary, in the LFP after WHF group, the response rate was 38.9% (CR 1, PR 6) and the one-year survival rate after LFP started was 46.0%. We conclude that the LFP therapy may be effective for the treatment of liver metastases from colorectal cancer even after the WHF therapy.     

Regional intra-arterial infusion in combination chemotherapy with IFN-beta, MMC and 5-FU (beta-MF chemotherapy) in liver tumors

The effect of combination chemotherapy with Interferon-beta, Mitomycin C and 5-fluorouracil (beta-MF chemotherapy) on 7 hepatic tumors by intra-arterial administration was studied. Complete remission (CR) was observed in one patient and partial remission (PR) in two patients, the efficacy rate being 42.9%. The survival period was more than one year in 6 patients. Fever was observed in 6 cases, although it was slight in all cases and preventable by pre-treatment with antipyretics. The authors consider that beta-MF chemotherapy can be expected to be one form of treatment for nonresectable gastrointestinal carcinoma.     

A case of advanced gastric cancer with liver metastasis completely responding to CPT-11+low-dose 5-FU+CDDP chemotherapy

The case was a 54-year-old man with type-3 gastric cancer in the cardia accompanied by multiple liver metastasis. He received combination chemotherapy consisting of CPT-11 (60 mg/body, day 1 and 8)+low-dose 5-FU and CDDP (5-FU 500 mg/body/day and CDDP 5 mg/body/day, day 1-5 and 8-12, continuous infusion) every 3 weeks. The initial 2 courses were administered on an inpatient basis,and further courses as an outpatient. After 7 courses of therapy without severe adverse events, not only primary lesion but also hepatic metastasis disappeared. He has been free from disease for 4 months, and chemotherapy was further continued with TS-1 (100 mg/body, day 1-14)+CPT-11 60 mg/body, day 1, 8), every 3 weeks. CPT-11 in combination with low-dose 5-FU+CDDP can be one of the most effective regimens for unresectable advanced gastric cancer.     

A case of successful treatment by low-dose 5-fluorouracil and cisplatin for liver metastases of esophageal adenosquamous carcinoma

Adenosquamous carcinoma of the esophagus is an uncommon type of esophageal tumor. In the present case, a 54-year-old man without symptoms was diagnosed with esophageal squamous cell carcinoma, based on endoscopic examination of a biopsy specimen. Endoscopy and barium roentgenography revealed a superficial plateau-type lesion, 2 cm in length, in the lower esophagus. Esophagectomy with lymphadenectomy was performed via a right thoraco-abdominal approach. The histological diagnosis was adenosquamous carcinoma with no lymph node metastasis. Three years after the surgery, multiple liver metastases were detected by computed tomography. The patient was treated with a combination of low-dose 5-fluorouracil(350 mg/body/day) and low-dose cisplatin (7 mg/body/day). Because the first course of chemotherapy was very effective and the number of liver metastases was reduced,a further 6 courses were administered. After 6 courses of chemotherapy, no liver metastases were detected. Based on the present findings, we recommend low-dose 5-fluorouracil/cisplatin therapy for liver metastasis from esophageal adenosquamous carcinoma.     

Successful treatment of liver metastasis and extrahepatic metastasis with hepatic arterial infusion of CDDP, CPT-11, and 5-FU

A 63-year-old man, who had been operated with right hemicolectomy 1 year and 3 months ago, had giant liver metastasis, lung metastasis, and local dissemination tumor due to ascending colon cancer. He was treated by systemic chemotherapy with 5-FU and the treatment evaluation was PD on CT. After admission to our hospital, he was treated by hepatic arterial infusion chemotherapy with CDDP, CPT-11, and 5-FU. After 3 courses of the treatment, each recurrent lesion decreased on CT and the CEA level decreased. There were no side effects except mild diarrhea. We believe hepatic arterial infusion chemotherapy with CDDP, CPT-11, and 5-FU may be an effective strategy against liver metastasis and extrahepatic metastsis due to colon cancer.     

Preliminary clinical evaluation of continuous infusion of 5-FU and low-dose Cisplatin (LFP) therapy alone and combined with radiation therapy for treatment of advanced or recurrent esophageal cancer

We evaluated the clinical effect of 5-FU and low-dose Cisplatin (LFP) therapy alone and LFP therapy combined with radiation therapy in patients with advanced or recurrent esophageal cancer. From March 1995 to September 2000, 11 patients with inoperable esophageal cancer, 8 patients with adjuvant chemotherapy post operation, and 14 patients with recurrent esophageal cancer were treated with LFP therapy. 5-FU (160 mg/m2/day) was continuously infused over 24 hours, and CDDP (3-7 mg/m2/day) was infused for 30 minutes. The administration schedule consisted of 5-FU for 7 consecutive days and CDDP for 5 days followed by a 2-day rest, each for four weeks. We combined radiation therapy for the patients with all lesions that could be included in the radiation field. Of 30 patients with measurable lesions the response rates of LFP therapy alone and LFP therapy combined with radiation therapy were 33% and 60%, respectively. Toxicity over grade 3 appeared in 3 of 15 patients with LFP therapy combined with radiation therapy. There was no significant difference between LFP therapy alone and LFP therapy combined with radiation therapy with regard to survival rate of inoperable and recurrent esophageal cancer. In conclusion, LFP therapy alone may be effective for esophageal cancer.     

A case of recurrent gallbladder cancer responding to low-dose 5-FU and CDDP therapy

We treated a patient with a postoperative local recurrence of gallbladder cancer who showed a long-term response to low-dose 5-fluorouracil (5-FU) and cisplatin (CDDP) therapy. A 60-year-old woman was diagnosed with advanced gallbladder cancer, for which she underwent an extended cholecystectomy, bile duct resection and a partial resection of the duodenum in March 2000. The pathological diagnosis was well differentiated tubular adenocarcinoma of si, ly1, v1, hinf2, binf2, n0. Eight months later, she presented with cholangitis and obstructive jaundice due to a local recurrence of the gallbladder cancer and her serum CA19-9 level had increased to 1,991.6 U/ml. The biliary obstruction was treated by PTCD and a subsequent self-expanding metallic stent. In addition, she was also placed on combined chemotherapy with low-dose 5-FU and CDDP. Her serum CA19-9 level thereafter gradually decreased, so that after eight months it was within the normal range, and the recurrent tumor at the hepatic hilus was also observed to have decreased in size on the CT scan. As of this writing she has undergone eight courses of low-dose 5-FU and CDDP therapy over about a year and has been able to maintain a good quality of life without any severe adverse effects.     

A case of advanced cancer with liver metastasis and paraaortic lymph node metastasis responding remarkably to combination chemotherapy of low-dose CDDP, 5-FU and CPT-11

A 57-year-old male patient with upper epigastric discomfort was introduced to our hospital from another clinic because of gastric cancer. Several examinations showed massive liver metastasis and paraaortic lymph node metastasis from Type-3 gastric cancer beneath the posterior wall of the pyloric antrum. First we tried infusion of CDDP (10 mg/day for days 1-5 and 8-12) and continuous infusion of 5-FU (500 mg/day for 14 days). Concurrently, we added infusion of CPT-11 (80 mg/day on days 1,8). After 3 courses of chemotherapy, the tumor had decreased remarkably in size. Moreover, liver metastasis and paraaortic lymph node metastasis had vanished. This regimen thus appears to be effective for advanced gastric carcinoma.     

Clinical evaluation of intermittent hepatic arterial infusion therapy with CDDP and 5-FU for liver metastasis of colorectal cancer

Twenty-seven patients with liver metastasis from colorectal cancer were treated with intermittent intra-arterial infusion chemotherapy for 5 years starting from 1993. Five to ten mg of CDDP, 250 mg of 5-FU and/or 3-6 mg of Leucovorin were administered weekly. In the case of nonresponders, the dose of 5-FU was allowed to increase toward 500 mg. The above schedule was repeated as long as possible. The average number of administrations in 12 out of 27 unresectable patients was 28.7. The response rate was 50% (CR; 4 cases, PR; 2), with 2 NC and 3 PD. Four patients given 500 mg of 5-FU showed some response. The 50% survival period was 466 days, and the 1- and 3-year survival rates were 66.7% and 18.3%, respectively. The average number of administrations in the group of patients who underwent prophylactic treatment and resection of the metastasis was 33.1. During an average observational period 681 days, 7 patients (46.7%) had a recurrence in the liver. The 5-year survival rate was 85.7%. The patients who were treated with 250 mg 5-FU experienced no severe side effects, but one who was given 500 mg 5-FU developed a duodenal ulcer.     

食管癌肝转移的治疗疗效观察

目的 :探讨食管癌肝转移治疗疗效。方法 :对食管癌肝转移灶 18例行介入治疗 ,10例行单纯全身化疗。分析食管癌肝转移的治疗方式与生存时间的关系。结果 :1、2、3年生存率介入治疗组分别为 3 3 83 %、11 2 8%和0 ;单纯化疗组分别为 3 2 9%、10 69%和 0。两者生存期差异无统计学意义 ,P >0 0 5。结论 :介入治疗和全身化疗疗效差异无统计学意义 ,需根据病情进一步改进治疗方案     

A case of recurrent esophageal cancer successfully treated with concurrent radiochemotherapy with low-dose docetaxel plus 5-FU

A 70-year-old woman, who had undergone esophagectomy for cervical esophageal squamous cell carcinoma (pT3pN2M0, Stage III) 9 months earlier, was diagnosed as mediastinal lymph node recurrence by CT and endoscope. Patients underwent radiochemotherapy with 5 cycles of docetaxel 10 mg/m(2) on day 1 and 5-FU 250 mg/m(2) on day 1 to day 5, together with concurrent radiation (50 Gy/25 Fr) for mediastinum. After this treatment, a complete response (CR) was achieved, and there was no recurrence 9 months after the treatment. No severe adverse effects were observed. Concurrent radiochemotherapy with docetaxel and 5-FU is considered effective without serious side effects for postoperative recurrence in esophageal cancer.     

A trial of continuous and biweekly low-dose cisplatin and 5-FU with UFT chemotherapy for esophageal cancer

A 77-year-old man with advanced esophageal cancer with tracheal and esophageal obstruction underwent continuous low-dose FP chemotherapy for a total of seven weeks, resulting in a complete response (CR) and disappearance of the esophago-tracheal fistula. Since discharge from the hospital, he has maintained a stable good condition for about two years while receiving biweekly low dose FP chemotherapy and oral UFT. Eight patients who had post-operative recurrence and underwent noncurative operation for esophageal cancer were given low-dose FP chemotherapy. The results of this chemotherapy for those 8 patients and the present patient, for a total of 9 patients were 2 CR, 2 PR, 3 NC and 2 PD, with an overall response rate of 44%, and overall one-year and two-year survival rates of 44% and 22%, respectively.     

Preliminary clinical evaluation of low-dose CDDP and continuous 5-FU therapy for advanced gallbladder cancer

5-fluorouracil (5-FU) has been widely used for the treatment of gastrointestinal cancers. Low-dose cisplatin (CDDP) and continuous venous infusion of 5-FU have recently shown additive or synergistic antitumor effects in experimental models. In this study, we evaluated the clinical effects of low-dose CDDP and 5-FU (low-dose FP therapy) in patients with advanced gallbladder cancer. From December, 1993 to June, 1998, 13 patients with advanced gallbladder cancer were treated with low-dose FP therapy. Patients were eligible for this study if they had a bidimensionally measurable tumor. 5-FU (160 mg/m2/day) was continuously infused over 24 hours using an implantable port, and CDDP (3 mg/m2/day) was infused for one hour. The administration schedule consisted of 5-FU for 7 consecutive days and CDDP for 5 days followed by a 2-day rest, each for four weeks according to response and tolerance. Low-dose FP therapy was given to 12 patients (92.3%). The response rate was 66.7% and the median survival time was 151 days. The regimen was tolerable, with the most common toxicity being nausea (38.5%). There were no severe side effects except for one patient who suffered from grade 3 nausea. We conclude that low-dose FP therapy may be useful as a palliative chemotherapy for cases of advanced gallbladder cancer.     

Complete regression of esophageal cancer with concomitant liver metastasis achieved by concurrent chemoradiation therapy

 We report a patient with esophageal cancer with concomitant liver metastasis in whom complete response was achieved by chemoradiation therapy. A 66-year-old man was diagnosed as having stage IVB esophageal cancer with synchronous metastasis in the liver and cardiac lymph node, and concurrent chemoradiation therapy was started. The chemotherapy, consisting of 5-fluorouracil (300 mg/body per day, continuous infusion) and low-dose cisplatin (5 mg/body per day on 1–5 days every week), was performed for 7 weeks. In addition, radiation therapy (2 Gy/day on 1–5 days every week) was employed for both the local and the metastatic lesions, along with the chemotherapy. Throughout the course of this therapy, the patient did not experience severe toxicity, and this chemoradiation therapy resulted in complete regression of both the local and the metastatic diseases. Subsequently, he was followed-up as an outpatient without any maintenance therapy, and he has been free of disease for 38 months after completion of the therapy. This concurrent chemoradiation therapy may be effective for esophageal cancer even with visceral metastasis. Received: May 31, 2001 / Accepted: March 6, 2002