A new chemotherapeutic regimen for advanced unresectable hepatocellular carcinoma

BACKGROUND/AIMS: The aim of this study was to evaluate the efficacy and toxicity of a novel chemotherapeutic regimen for advanced unresectable hepatocellular carcinoma. METHODOLOGY: Seventeen patients with unresectable hepatocellular carcinoma were treated by arterial infusion once a week of low-dose cisplatin (12 mg/m2) and doxorubicin (6 mg/m2) via a subcutaneously implanted injection port and by daily oral administration of 300 mg/day of UFT comprising 5-fluorouracil prodrug tegafur (FT) and uracil (U) at a ratio of 1:4. RESULTS: The median number of chemotherapy courses was 13 (range, 5-33). All patients were evaluated for response, toxicity, and survival. As assessed by conventional imaging criteria, there were 3 (17.6%) complete responses with disappearance of the primary tumor, tumor thrombosis of the portal vein and metastatic para-aortic lymph node swelling. In addition, there were 4 (23.5%) partial responses. Among 11 patients who had initially high alpha-fetoprotein levels (> 200 ng/mL), 5 (45%) had a > 50% drop after therapy. The overall tumor response rate (complete response + partial response) was 41% and the median survival was 7.1 (range; 4.2-25.1) months. As for toxicity, there was 1 treatment-related death due to septicemia caused by catheter-related infection. Myelosuppression and renal toxicity was relatively mild and transient. CONCLUSIONS: These results suggest that our low-dose chemotherapeutic regimen may be useful for the treatment of advanced unresectable hepatocellular carcinoma without worsening the quality of life of the patient.     

Complete disappearance of pulmonary metastases in a case of hepatocellular carcinoma treated with docetaxel-based systemic chemotherapy

A case of the complete shrinkage of pulmonary metastases from multiple hepatocellular carcinomas (HCC) after administration of docetaxel, cisplatin and enteric-coated tegafur/uracil is reported. A 54-year-old Japanese man was diagnosed with recurrent multiple HCC associated with pulmonary metastases and compensated liver cirrhosis. Docetaxel, cisplatin and enteric-coated tegafur/uracil were given to this patient. After 2 months of treatment, there was a decrease in tumor markers and a shrinkage of the pulmonary metastases. Image analyses such as chest X-rays and chest computed tomography scans showed a disappearance of the pulmonary metastases, although the multiple HCC did not disappear completely. This was evaluated as a complete remission of metastatic lesions or a partial remission of primary lesions according to the World Health Organization criteria. No recurrence of pulmonary metastasis was seen for 10 months. This combination therapy was well-tolerated for lung cancer and could represent an effective treatment for pulmonary metastases from HCC.     

Improved survival with oral administration of enteric-coated tegafur/uracil for advanced stage IV-A hepatocellular carcinoma

BACKGROUND AND AIMS: There is currently no proven chemotherapy regimen for hepatocellular carcinoma (HCC). The principal chemotherapeutic approach in most cases is infusion therapy into the hepatic arteries feeding the tumors. However, the clinical effects of chemotherapy are extremely poor. Therefore, in the present study, we conducted a prospective randomized trial of the efficacy of oral administration of enteric-coated tegafur/uracil for advanced HCC. METHODS: From 1994 to 1999, a total of 56 consecutive patients with unresectable stage IV-A HCC were studied prospectively to examine the efficacy of enteric-coated tegafur/uracil in HCC and to determine the significant prognostic factors. Twenty-eight patients were treated only with enteric-coated tegafur/uracil without other anticancer treatment. Another 20 patients were given conservative management only. The remaining eight patients withdrew from the study. RESULTS: In the group treated only with enteric-coated tegafur/uracil, the median survival time and 1 and 2 year survival rates were 12.13 months and 55.3 and 36.9%, respectively. In the control group, the median survival time and 1 year survival rate were 6.20 months and 5.5%, respectively. By both univariate analysis and multivariate analysis using Cox's proportional hazards model, treatment with enteric-coated tegafur/uracil was shown to be the factor most significantly favoring a better prognosis. CONCLUSIONS: Although the prognosis of most patients with stage IV-A HCC is poor, administration of enteric-coated tegafur/uracil induces long-term survival and is an effective treatment for stage IV-A HCC.     

A combination immunochemotherapy of 5-fluorouracil, cisplatin, leucovorin, and OK-432 for advanced and recurrent gastric carcinoma

BACKGROUND/AIMS: Based on theories of biochemical modulation and immunotherapy, a novel regimen consisting of 5-fluorouracil, cisplatin, leucovorin, and OK-432 (FLPO therapy) was devised for the treatment of patients with advanced and recurrent gastric carcinoma. METHODOLOGY: The 14-day combination therapy consisted of continuous infusion of 5-fluorouracil (250 mg/m2/day), a bolus injection of 10 mg cisplatin and 30 mg leucovorin every other day, and a subcutaneous injection or per oral administration of OK-432 (3KE or 5KE) every other day. Thirty patients completed 59 courses of treatment consisting of 2 weeks of therapy followed by at least 2 weeks rest. RESULTS: The overall response rate was 40%, with 1 complete response and 11 partial responses observed. All twelve patients responded after 1 course of treatment. The response rate differed depending upon tumor location, 22.2% at the primary site, 60.0% in the lymph nodes, 45.5% with peritoneal dissemination, 44.4% with liver metastases, 50.0% in the lung, and 100.0% with skin metastases. The most frequently observed toxicity was stomatitis (53.3%). The overall incidence of toxicities of grade 3 or greater was 6.6%, including diarrhea (3.3%) and stomatitis (3.3%). One patient required treatment interruption because of the grade 3 toxicity of diarrhea. The median survival time was 198 days overall, 242 days for responders and 125 days for non-responders. CONCLUSIONS: FLPO therapy seemed to be an effective regimen for the treatment of advanced and recurrent gastric carcinoma.     

Successful treatment of multiple lung metastases of hepatocellular carcinoma by combined chemotherapy with docetaxel, cisplatin and tegafur/uracil

We report the successful treatment of multiple lung metastases after hepatic resection for hepatocellular carcinoma （HCC） with combined docetaxel, cisplatin （CDDP）, and enteric-coated tegafur/uracil （UFT-E）. A 68-year-old man was diagnosed with multiple lung metastases of HCC 7 mo after partial hepatectomy for HCC. Oral UFT-E was given daily and docetaxel and CDDP were given intra-arterially （administered just before the bronchial arteries） every 2 wk via a subcutaneous injection port. One month after starting chemotherapy, levels of tumor marker, protein induced by vitamin K absence Ⅱ （PIVKA-Ⅱ ）, decreased rapidly, and after a further month, chest X-ray and computed tomography revealed the complete disappearance of multiple liver metastases. Two years after the combined chemotherapy, HCC recurred in the liver and was treated but no pulmonary recurrence occurred. In the absence of a standardized highly effective therapy, this combined chemotherapy with docetaxel, CDDP and UFT-E may be an attractive option for multiple lung metastases of HCC.     

Complete remission of multiple hepatocellular carcinomas associated with hepatitis C virus-related, decompensated liver cirrhosis by oral administration of enteric-coated tegafur/uracil

We report a case of complete remission of multiple hepatocellular carcinomas after oral administration of enteric-coated tegafur/uracil. A 77-yr-old woman was diagnosed as having recurrent hepatocellular carcinoma associated with decompensated liver cirrhosis. We administered enteric-coated tegafur/uracil to this patient. After 1 month of oral administration, there was a decrease in tumor markers. An image analysis showed disappearance of hepatocellular carcinoma. No recurrence of the hepatocellular carcinoma was recognized for 18 months up to the time of the patient's death, which was due to massive bleeding from a hemorrhagic rectal ulcer. At autopsy, the tumor lesion had necrotized. Oral administration of enteric-coated granules containing tegafur/uracil may provide an effective treatment for hepatocellular carcinoma.     

Adjuvant therapy with protein-bound polysaccharide K and tegafur uracil in patients with stage II or III colorectal cancer: randomized,controlled trial

PURPOSE: Intravenous fluorouracil and leucovorin for six to eight months is currently a standard adjuvant treatment for Stage III colon cancer; however, this regimen is complex, inconvenient, and has a high intolerability. Adjuvant chemotherapies are claimed for objective response rates with an acceptable safety profile and complexity. We investigated the benefits of oral protein-bound polysaccharide K added to oral tegafur/uracil on curatively resected Stage II or III colorectal cancer. METHODS: We prospectively randomized 207 patients to treatments of either oral 3.0 g protein-bound polysaccharide K plus 300 mg tegafur/uracil or 300 mg tegafur/uracil alone for two years following 12 mg/m² and 8 mg/m² mitomycin treatment on postoperative Days 1 and 2, respectively. The primary end points were disease-free and overall survival, and recurrence rates. RESULTS: Three (1.4 percent) patients were declared ineligible, and three patients did not start treatment. In total, 201 patients were analyzed. The three-year, disease-free survival rate was 80.6 percent (standard error = 3.4 percent) in the protein-bound polysaccharide K group (P = 0.02) compared with 68.7 percent (SE = 5.7 percent) in the control group after a median follow-up of 3.7 years. The estimated relative risk of recurrence in the control group was 1.87 (95 percent confidence interval, 1.10–3.20) at three years. The three-year, overall survival rate was 87.3 percent (standard error = 2.9 percent) in the protein-bound polysaccharide K group and 80.6 percent (standard error = 4.8 percent) in the control group (P = 0.24). The three-year, overall survival rate in 80 pathological TNM Stage III patients was 83.0 percent (standard error = 5.2 percent) in the protein-bound polysaccharide K group and 59.3 percent (standard error = 9.5 percent) in the control group (P = 0.02). Protein-bound polysaccharide K prevented distant metastases (P = 0.05), particularly lung metastases (P = 0.01). The incidence of adverse effects was minimal, and compliance was good. CONCLUSION: Adjuvant therapy using a combination of oral protein-bound polysaccharide K and tegafur/uracil is highly effective in preventing the recurrence of colorectal cancer in Stage II or III patients, and increases overall survival in pathological TNM Stage III. These results will be a sufficient proof to conduct a larger study to compare tegafur/uracil/protein-bound polysaccharide K with 5-fluorouracil/ leucovorin.     

Peritoneal dissemination of hepatocellular carcinoma treated with a combination therapy of interferon-alpha-2b and oral tegafur/uracil

We encountered a case of peritoneal dissemination of hepatocellular carcinoma, successfully treated with a combination therapy of interferon-alpha-2b and oral tegafur/uracil. A 67-year-old Japanese man who underwent a hepatectomy developed peritoneal dissemination. A combination therapy of subcutaneous interferon-alpha-2b and intravenous 5-fluorouracil was started. Four weeks later, he felt severe general fatigue and nausea, and intravenous 5-fluorouracil was replaced with oral tegafur/uracil. At 3 months after the initiation of chemotherapy, enhanced computed tomography showed markedly reduced peritoneal dissemination. A combination therapy of interferon-alpha-2b and oral tegafur/uracil is facile and may be effective for extrahepatic metastasis of hepatocellular carcinoma.     

Complete response to treatment with hepatic arterial infusion of cisplatin powder (IA-call) in a case of hepatocellular carcinoma with multiple lung metastases]

A 74-year-old woman was admitted to our hospital to treat her hepatocellular carcinoma (stage IVB) with multiple lung metastases. She was treated with 3 times of hepatic arterial infusion of cisplatin powder (IA-call). After the treatment, liver mass and lung tumors were disappeared and high levels of tumor markers (AFP and PIVKA-II) were markedly decreased. These data revealed that a complete response (CR) was obtained for her. She has still been maintained in CR for 2 years since the first treatment.     

Complete disappearance of recurrent hepatocellular carcinoma with peritoneal dissemination and splenic metastasis: a unique clinical course after surgery

Spontaneous regression of hepatocellular carcinoma (HCC) is a rare phenomenon. We report a case of complete disappearance of intrahepatic, peritoneal and splenic metastases in HCC after hepatectomy using treatment with tegafur and uracil (UFT). The effect of UFT alone was not likely to have caused the disappearance of this tumour because HCC recurrence advance markedly within 5 months of surgery despite oral administration of UFT. This case demonstrates a unique postoperative clinical course that suggests spontaneous regression of HCC. This is the first case of complete disappearance of unresectable HCC with peritoneal seeding and splenic metastasis.     

Treatment of hepatocellular carcinoma by transcatheter arterial embolization combined with intraarterial infusion of a mixture of cisplatin and ethiodized oil

The therapeutic effectiveness of transcatheter arterial embolization (TAE) with intraarterial infusion of cisplatin/ethiodized oil mixture in treatment of resectable and unresectable hepatocellular carcinoma was compared with TAE with intraarterial infusion of doxorubicin mixed with and without ethiodized oil. The series included 97 patients with unresectable hepatocellular carcinoma and 40 patients with resectable hepatocellular carcinoma. With TAE using doxorubicin infusion, a partial response of the tumor was seen in only 11%, and the 2-yr survival was calculated to be only 5%. Histologic examination of the specimens obtained by hepatectomy also showed that this treatment was relatively ineffective in daughter tumor and portal tumor thrombi. In contrast, TAE with infusion of cisplatin/ethiodized oil mixture significantly increased the rate of partial response (38%), and significantly prolonged the 2-yr survival (45%). Histologically this treatment gave severe necrosis in daughter tumors (69%) and tumor thrombi (78%) as well as main tumor (75%). This treatment was significantly better than TAE with doxorubicin and ethiodized oil infusion in terms of the tumor regression and histologic responses of main tumor and portal vein tumor thrombi, but not in terms of the 2-yr survival. However, 2 patients (8%) died within 4 wk of the latter treatment, whereas no deaths were reported after the former treatment. Therefore, TAE combined with intraarterial infusion of cisplatin/ethiodized oil mixture may be a safe and useful treatment modality for hepatocellular carcinoma.     

An autopsy case of multilocular cystic hepatocellular carcinoma without liver cirrhosis

Although simple cysts, cystadenoma and cystadenocarcinoma of the liver have been well documented as hepatic cystic diseases, cystic hepatocellular carcinoma is a curious entity. Only 3 cases have been reported in the English literature. A 70-year-old man was admitted to Nagoya University Hospital for multiple liver tumors and a thrombus in the main trunk of the portal vein. A part of the tumors contained cystic components, and were diagnosed as hepatocellular carcinoma by needle biopsy. After giving informed consent, the patient was treated with several systemic chemotherapy using doxorubicin, fluorouracil, cyclophosphamide, cisplatin and oral anticancer agent UFT, a combination of uracil and tegafur, for almost 2 years. During this time, the tumors enlarged gradually, and also underwent cyst formation, the patients then died of biliary sepsis. Autopsy confirmed the diagnosis of multilocular cystic hepatocellular carcinoma without liver cirrhosis.     

Improved survival for hepatocellular carcinoma with portal vein tumor thrombosis treated by intra-arterial chemotherapy combining etoposide, carboplatin, epirubicin and pharmacokinetic modulating chemotherapy by 5-FU and enteric-coated tegafur/uracil： A pilot study

AIM： To investigate the poor prognosis of HCC with PVTT, we evaluated the efficacy by a new combination chemotherapy for advanced hepatocellular carcinoma （HCC） with portal vein tumor thrombus （PVTT）.
METHODS： From 2002 to 2007, a total of 10 consecutive patients with Stage IVA HCC accompanied by PVTT were studied prospectively to examine the efficacy of treatment by intra-arterial infusion of a chemotherapeutic agents consisting of etoposide, carboplatin, epirubicin and pharmacokinetic modulating chemotherapy by 5-FU and enteric-coated tegafur/uracil.
RESULTS： The mean course of chemotherapy was 14.4 （range, 9-21） too. One patient showed complete response （CR） with disappearance of HCC and PVI-F after treatment, and the two patients showed partial response （PR）, response rate （CR ＋ PR/All cases 30%）. The median survival time after the therapy was 457.2 d. The one-year survival rate was 70%. Adverse reactions were tolerable.
CONCLUSION： Although the prognosis of most patients with Stage IVA HCC by PVTT is poor, our combination chemotherapy may induces long-term survival and is an effective treatment and produced anti-tumor activity with tolerable adverse effects in patients for advanced Stage IVA HCC accompanied by PVTT.     

Improved survival for hepatocellular carcinoma with portal vein tumor thrombosis treated by intra-arterial chemotherapy combining etoposide, carboplatin, epirubicin and pharmacokinetic modulating chemotherapy by 5-FU and enteric-coated tegafur/uracil: A p

AIM: To investigate the poor prognosis of HCC with PVTT, we evaluated the efficacy by a new combination chemotherapy for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).METHODS: From 2002 to 2007, a total of 10 consecutive patients with Stage IVA HCC accompanied by PVTT were studied prospectively to examine the efficacy of treatment by intra-arterial infusion of a chemotherapeutic agents consisting of etoposide, carboplatin, epirubicin and pharmacokinetic modulating chemotherapy by 5-FU and enteric-coated tegafur/uracil.RESULTS: The mean course of chemotherapy was 14.4 (range, 9-21) mo. One patient showed complete response (CR) with disappearance of HCC and PVTT after treatment, and the two patients showed partialresponse (PR), response rate (CR + PR/All cases 30%).The median survival time after the therapy was 457.2 d. The one-year survival rate was 70%. Adverse reactions were tolerable.CONCLUSION: Although the prognosis of most patients with Stage IVA HCC by PVTT is poor, our combination chemotherapy may induces long-term survival and is an effective treatment and produced anti-tumor activity with tolerable adverse effects in patients for advanced Stage IVA HCC accompanied by PVTT.     

Chemotherapy of cerebral metastasis of lung cancer

Between November 1983 and November 1988, 60 patients with cerebral metastases arising from primary lung cancer were treated with chemotherapy. Thirty patients received a 5-day course of cisplatin (total dose: 200 mg/sq.m). The remaining 30 patients received VP 16 in doses of 250 mg/sq.m. administered 12-hourly by intravenous infusion over one hour (total dose: 1,500 mg/sq.m.). Twenty-seven percent of the patients who received cisplatin showed objective responses as assessed by computerized tomography; 10% had serious toxic reactions. Thirty percent of the patients who received VP 16 showed objective responses, but 43% had severe bone marrow aplasia resulting in a 33% death rate due to infection. The median survival of responders was 8 months in both treatment groups. The objective response rates as assessed by histology were 33% in patients with oat-cell carcinoma and 27% in patients with other histological types. VP 16 must be abandoned, being too toxic in high doses. High-dose cisplatin can be used in the treatment of cerebral metastases of lung cancer, side by side with radiotherapy.     

Prognostic factors for disease-free survival in pT2N0 non-small cell lung cancer

To clarify the prognostic factors for disease-free survival in completely resected pT2N0 non-small cell lung cancer, 81 consecutive patients who were treated between 1998 and 2001 were retrospectively reviewed. Follow-up was complete for all patients and the median follow-up time was 37.5 months. The overall 5-year survival rate was 68.6%, and the 5-year disease-free survival rate was 62.5%. Four factors (age, sex, visceral pleural invasion, and administration of tegafur and uracil) were proposed as prognostic factors for disease-free survival by univariate analysis. In multivariate analysis, visceral pleural invasion by the tumor (hazard ratio = 2.709, 95% confidence interval: 1.085 to 6.765, p = 0.033) and administration of tegafur and uracil (hazard ratio = 0.327, 95% confidence interval: 0.147 to 0.730, p = 0.006) were significant factors. Visceral pleural invasion was a prognostic factor for reduced disease-free survival in completely resected pT2N0 non-small cell lung cancer, and postoperative treatment with tegafur and uracil significantly improved disease-free survival.     

Complete remission of a case of hepatocellular carcinoma with tumor invasion in inferior vena cava and with pulmonary metastasis successfully treated with repeated arterial infusion chemotherapy

We report the case of a patient having hepatocellular carcinoma with tumor invasion to the inferior vena cava and with multiple pulmonary metastases who was treated with repeated one-shot administration of epirubicin, cisplatin, and mitomycin C by hepatic artery and bronchial artery, which led to complete remission. A 72-year-old woman was diagnosed with infiltrative hepatocellular carcinoma with Vv3, multiple intrahepatic metastases, and multiple pulmonary metastases associated with compensated liver cirrhosis. One-shot infusion of epirubicin, cisplatin, and mitomycin C was performed through proper hepatic artery and bronchial artery for twice at eight weeks of intervals. Pulmonary metastases disappeared and intrahepatic lesions indicated marked shrinkage leaving a scar-like lesion with decreases in tumor markers. After six months and 20 months, tumor markers indicated increasing tendency but no evident recurrence was found by computed tomography or hepatic arteriography. One-shot infusion of the same regimens through proper hepatic artery was performed and tumor markers decreased to normal levels. After 14 months of the last therapy, no evidence of recurrence has been found on image analysis or in tumor markers. This arterial infusion therapy is well tolerated for the patients with compensated liver cirrhosis and might be promising for the effective treatment of advanced hepatocellular carcinoma with pulmonary metastases.     

Pilot study of systemic combination therapy with S-1, an oral fluoropyrimidine, and cisplatin for hepatocellular carcinoma with extrahepatic metastases

BACKGROUND/AIMS: The aim of this pilot study was to elucidate the efficacy and safety of systemic combination therapy with S-1 and cisplatin (CDDP) for hepatocellular carcinoma (HCC) patients with extrahepatic metastases. METHODOLOGY: Sixteen patients were enrolled in this pilot study. Two weeks of combination therapy represented one cycle, followed by two-to-four weeks rest. In each cycle, S-1 was administrated orally at 80-120 mg (depending on body surface area) every day and cisplatin was administrated intravenously at 60 mg/m2 on day 8. Response, overall survival and adverse effects were assessed. RESULT. No patient had intrahepatic HCC and all patients had a class A Child-Pugh score. Regarding overall response, 2 (13%), 0 (0%), 5 (31%), and 9 (56%) patients showed complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD), respectively, giving an overall response rate of 13% (2/16). The overall survival rate at 12 months was 77%. With regard to NCI-CTC grade-3 adverse reactions, 2 (13%), 2 (13%), and 6 (38%) patients developed nausea, anorexia, and neutropenia, respectively. No grade-4 adverse reaction or toxicity-related death occurred. CONCLUSION; S-1/CDDP is a potentially safe and effective combination therapy for HCC patients with extrahepatic metastases.     

Hand-foot syndrome associated with uracil/tegafur and docetaxel in a patient with lung cancer]

A 30-year-old woman given a diagnosis of stage IV lung adenocarcinoma, was admitted to our hospital because of chest pain due to pleuritis carcinomatosa. She had taken uracil/tegafur (UFT) 600mg orally every day from September 2004. Uracil/tegafur was stopped in December 10, 2005, and docetaxel (taxotere) 50mg/m2 was given in December 12, 2005. Seven days after treatment with docetaxel she developed erythema and spontaneous pain of the palms and fingers of both hands and soles of both feet. The erythema increased gradually, and 10 days after docetaxel infusion she could not walk due to severe pain. After improvement of the painful erythema, desquamation of fingers of both hands and the soles of both feet occurred. She was diagnosed with hand-foot syndrome. Although the same amount of docetaxel was given later, hand-foot syndrome was not seen. Therefore it was suggested that both uracil/tegafur and docetaxel induced hand-foot syndrome. Fluoropyrimidines and taxanes have been reported as common anti-cancer drugs that lead to hand-foot syndrome. Since these drugs play a crucial role in lung cancer treatment, we need to pay attention to hand-foot syndrome. A sufficient off-drug period is required in the sequential usage of fluoropyrimidines and taxanes.     

Phase II study of uracil-tegafur plus cisplatin in patients with previously untreated advanced non-small cell lung cancer

Background and objective:   A multi-institutional phase II trial combining uracil-tegafur (UFT) and cisplatin (CDDP) was conducted in patients with previously untreated advanced non-small cell lung cancer (NSCLC) to evaluate the safety and efficacy of this combined treatment regimen.
Methods:   The entry criteria for this study were previously untreated NSCLC, measurable disease, age <80 years, performance status <2, and adequate haematological, hepatic and renal function. Patients were treated with 400 mg/m² oral UFT from day 1 to day 14 and 80 mg/m² cisplatin on day 15. The treatment course was repeated every 3 weeks.
Results:   Of the 68 patients enrolled, 64 (27 with stage IIIB and 37 with stage IV disease) were eligible for treatment. Twenty of the 64 patients responded to the chemotherapy (response rate 31.3%; 95% CI 21.2–43.4%). The median survival time was 8.6 months, and the 1-year survival was 41.5%. Haematological toxicity ≥WHO grade 3 was seen in 3 (4.7%) patients. For non-haematological toxicities, anorexia with WHO grade 3 was seen in 8 (12.5%) patients, nausea and vomiting with WHO grade 3 in 4 (6.3%), diarrhoea with WHO grade 4 in 1 (1.6%), and liver dysfunction with WHO grade 4 in 1 (1.6%) patient.
Conclusions:   The combination of oral UFT plus cisplatin was found to be a safe and active treatment against advanced NSCLC. The observed low toxicity of this combined regimen may warrant its application to the treatment of elderly patients.