A phase II trial of 5-fluorouracil and cisplatinum in recurrent or metastatic nasopharyngeal carcinoma

Background: A phase II clinical trial of the combination of5-fluorouracil (5-FU) and cisplatinum (CDDP) was conducted in24 patients (pts) with recurrent or metastatic nasopharyngealcarcinoma. None of the patients had prior chemotherapy and allbut 4 had prior radiotherapy. Patients and methods: 5-FU was administered by intravenous (i.v.)infusion at a dose of 1000 mg/m² daily on days 1 to 5 and i.v.infusion of CDDP at a dose of 100 mg/m2 in divided doses ondays 1 to 3 of each 21-day cycle. Pts were examined for responseafter every two cycles. Of 24 pts accrued, 21 had measurabledisease. Three had only bone metastases and were evaluable fortoxicity and survival. Results: Thirteen pts had partial response and three achievedcomplete response, for an overall response rate of 66% (95%confidence interval 59% to 93%). Median time to progressionfor all patients was 8 months (range 4 to 28+ months) and mediansurvival for all patients was 11 months. Grades 3 to 4 toxicitiesincluded granulocytopenia (10 pts). There was no treatment-relatedmortality. Average relative dose intensity was 0.8. Conclusion: This combination is highly effective with acceptabletoxicity. The duration of response tended to be brief. Its rolein the neoadjuvant and adjuvant setting in patients with poorprognostic features should be further studied. 5-fluorouracil, cisplatinurn, nasopharyngeal carcinoma     

Phase II trial of 5-fluorouracil, leucovorin and cisplatin for treatment of advanced pancreatic adenocarcinoma

Background. Advanced pancreatic adenocarcinoma is a rapidlyfatal disease for which an active chemotherapy regimen is sought.Here we report the outcome of a phase II trial to assess thetoxicity and efficacy of a combination of 5-flu-orouracil (5-FU),leucovorin and cisplatin (CDDP). Methods. A regimen combining leucovorin (200 mg/m²/d x 5d),5-FU (375 mg/m²/d x 5d in a 2-hour infusion) and CDDP (15 mg/m²/dx 5d) was given to 52 patients with histologically-proven, previouslyuntreated, locally advanced (n = 13) and/or metastatic (n =39) pancreatic adenocarcinoma. Results. Of 48 patients evaluable for response, 10 achievedpartial responses, for an overall response rate of 21% (95%CI 9.5%–32.5%), and a palliative effect was observed in52%. The median survival was 9.5 months (18 months for locally-advancedand 5 months for metastatic disease) with a 1-year survivalof 34.6% and a median progression-free survival of 4.5 months.Chemotherapy was well tolerated with grades 3 or 4 nausea/vomitingin 12%, diarrhea in 6%, anaemia in 17%, neutropenia in 12%,and thrombocytopenia in 10%. Eleven patients (21%) had Grade2 peripheral neuropathy. Conclusion. The combination of leucovorin, 5-FU and CDDP seemsto be an effective palliative treatment, with moderate toxiceffects, in advanced pancreatic adenocarcinoma. advanced pancreatic adenocarcinoma, cisplatin, 5-fluorouracil, leucovorin     

A Phase I Trial of 5-Fluorouracil with Cisplatin and Concurrent Standard-dose Radiotherapy in Japanese Patients with Stage II/III Esophageal Cancer

Objective: In Japan, 5-fluorouracil (5-FU) 400 mg/m² on Days 1–5,8–12, 36–40 and 43–46 with cisplatin (CDDP)40 mg/m² on Days 1, 8, 36 and 43 plus concurrent radiotherapywith 2 weeks planned interruption (60 Gy) was standard for thepatients with esophageal cancer. This Phase I trial was designedto determine the maximal tolerated dose (MTD) and dose-limitingtoxicity (DLT) of 5-FU on Days 1–4 and 29–32 withCDDP on Days 1 and 29 plus concurrent radiotherapy (50.4 Gy)among the Japanese. Methods: Escalating doses of 5-FU and CDDP were administered with concurrentradiotherapy (50.4 Gy). Treatment was continued until DLT appeared. Results: Twelve patients with previously untreated clinical Stage II/IIIsquamous cell esophageal carcinoma were studied. One of sixpatients given Level 1 (5-FU 800 mg/m² on Days 1–4 and29–32 with CDDP 75 mg/m² on Days 1 and 29) developed aDLT of incomplete protocol treatment due to Grade 3 esophagitis.The MTD was not reached at Level 2 (5-FU 1000 mg/m² with CDDP75 mg/m²). The complete response rate was 67% at Level 1 and100% at Level 2. Conclusions: Dose Level 2 with 50.4 Gy radiotherapy was recommended for Japanesepatients.     

A Phase I trial of arterial infusion chemotherapy with gemcitabine and 5-fluorouracil for unresectable advanced pancreatic cancer after vascular supply distribution via superselective embolization

Background: We previously reported that arterial infusion chemotherapy improvedthe response rate and survival of the patients with pancreaticcancer at advanced stages in an open trial. We conducted a PhaseI trial of arterial infusion chemotherapy with gemcitabine and5-fluorouracil for advanced pancreatic cancer after vascularsupply distribution via superselective embolization. Methods: Patients were treated after arterial embolization for hemodynamicchange to restrict the blood flow into the pancreas (mainlyto the great pancreatic artery and the caudal pancreatic artery).Arterial infusion chemotherapy consisted of gemcitabine in dosesthat were increased from 600 to 1000 mg/m² in subsequent cohortson Day 1 plus continuous infusion of 5-fluorouracil 300 mg/m²/dayon Days 1–5 every 2 weeks. Result: Twelve patients were enrolled. The maximum tolerated dose ofgemcitabine was determined to be Level 3 (1000 mg/m²). Onlyvery mild hematological and non-hematological toxicities werenoted. The overall response rate was 33.3%. The median survivaltime was 22.7 (95% CI; 9.5–24.5) months and the 1- and2-year overall survival rates were 83.3 and 25.0%, respectively. Conclusion: Arterial infusion chemotherapy using 1000 mg/m² gemcitabineon Day 1 and 300 mg/m²/day 5-fluorouracil on Days 1–5every 2 weeks warrants a Phase II study.     

Results of a randomized trial with or without 5-FU-based preoperative chemotherapy followed by postoperative chemotherapy in resected colon and rectal carcinoma

Background: Our previous study confirmed the efficacy of postoperativetreatment with mitomycin C (MMC) and oral 5-fluorouracil (5-FU)for colorectal cancer. The 2nd trial was designed to evaluatethe effectiveness of additional preoperative chemotherapy topostoperative treatment with MMC and oral 5-FU for curativelyresected colorectal cancer patients. Patients and Methods: 1355 patients (colon 755; rectum 600)were enrolled in this study. The pre- and postoperative chemotherapy(PPC) group was treated preoperatively with 5-FU (320 mg/m²/day)by continuous intravenous infusion for 5 days beginning on day6 before surgery and postoperatively with MMC (6 mg/m²) on days7 and 14 and in months 2, 4 and 6, by bolus injection and oral5-FU (200 mg/day) for 6 months. The postoperative chemotherapy(PC) group received postoperative chemotherapy only. Results: In an intent-to-treat analysis, the 5-year survivalrate in the PPC group and the PC group was 77.3% and 75.7% forcolon cancer and 67.2% and 69.2% for rectal cancer, respectively.In a per-protocol analysis, the 5-year DFS rate in the PPC groupand the PC group was 76.0% and 80.7% for colon cancer and 60.5%and 63.0% for rectal cancer, respectively, indicating no significantdifferences between the two groups. Adverse reactions were generallymild, confirming the safety of this preoperative chemotherapeuticregimen. Conclusion: In the PC group, the 5-year survival rate was nearlyidentical with that seen in our earlier research using the sameregimen, reaffirming the clinical effectiveness of postoperativeMMC by protracted intravenous infusion and oral 5-FU. However,our findings did not support additional preoperative chemotherapyfor curative resection in patients with colorectal cancer. ⁺ For participating physicians and institutions, see Appendix.      

Randomized controlled phase II comparison study of concurrent chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil versus CCRT with cisplatin, 5-fluorouracil, methotrexate and leucovorin in patients with locally advanced squamous cell carcinoma of the head and neck

We compared concurrent chemoradiotherapy (CCRT) with docetaxel, cisplatin (CDDP), and 5-fluorouracil (5-FU) (TPF) with CCRT with CDDP, 5-FU, methotrexate and leucovorin (PFML) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) in terms of safety and efficacy on survival. A total of 100 patients were enrolled. The TPF group received CCRT with the TPF regimen [docetaxel (50 mg/m²: day 1), CDDP (60 mg/m²: day 4), and continuous 5-FU infusion (600 mg/m²/day: days 1–5)]. In the PFML group, patients received CCRT with the PFML regimen [CDDP (60 mg/m²: day 4)], continuous 5-FU infusion (600 mg/m²/day: days 1–5), methotrexate (30 mg/m²: day 1) and leucovorin (20 mg/m²/day: days 1–5)]. Both groups received 2 cycles of chemotherapy during definitive radiotherapy. The total radiation dose was between 66.6 and 70.2 Gray. The overall response rates after CCRT were 98 with 90% of a pathologically complete response (pCR) in the TPF group and 94 with 77% in the PFML group. For grade 3/4 adverse events, mucositis was more frequent in the PMFL group, and the TPF group showed a higher incidence of hematological toxicity. CCRT with TPF or PMFL for advanced SCCHN was tolerable and produced excellent survival rates.     

Three successful case reports of advanced gastric cancer with chemotherapy

We report three successful cases with continuous systemic chemotherapy for advanced gastric cancer. Case 1: A 67-year-old male with gastric cancer. Abdominal CT showed the invasion in the pancreas and as a result, continuous systemic infusion of low-dose cisplatin (CDDP 20 mg/day) and 5-fluorouracil (5-FU 1,000 mg/day) was performed. This infusion chemotherapy, CDDP and 5-FU, was continued for 5 days and discontinued for 25 days. Three months after the chemotherapy, the main tumor was remarkably reduced (downstaging was obtained), and consequently, total gastrectomy was performed. Case 2: A 78-year-old male with gastric cancer and hepatic multiple metastases. Abdominal CT scan before operation did not reveal the hepatic metastasis. In the operation for distal gastrectomy, we found multiple metastases on the surface of the liver. Continuous systemic infusion of low-dose CDDP (20 mg/day) and 5-FU (1,000 mg/day) was performed. This infusion chemotherapy, CDDP and 5-FU, was continued for 5 days and discontinued for 2 days. One month after the chemotherapy, Liver metastases had almost disappeared. Case 3: A 73-year-old male had received a distal gastrectomy based on the diagnosis of gastric cancer. The tumor marker, CA19-9, immediately decreased after the operation, but had increased again. He was treated with a combination chemotherapy of TS-1 and CDDP. The treatment consisted of 4 weeks of TS-1 administration (100 mg daily) followed by a 2-week break. CDDP of 10 mg/day was infused intravenously (day 1-5). Four weeks after the infusion, CA19-9 had returned to almost normal. We conclude that the combination chemotherapy of 5-FU (or TS-1) and CDDP might be an effective treatment for advanced and metastatic gastric cancer.     

Outpatient weekly high-dose continuous-infusion 5-fluorouracil plus oral leucovorin in advanced colorectal cancer. A phase II trial

BACKGROUND:: Background: In a previous phase I–II trial we showed thatmaximum tolerable dose (MTD) of 5-fluorouracil (5-FU) a weekly48-hour continuous infusion (CI) was 3.5 g/m². In a subsequentconfirmative phase II trial with 85 evaluable patients, a 38.5%response rate was obtained, and a median survival of 12 months.These data were comparable to those achieved by biochemicalmodulation of 5-FU with leucovorin. On this basis we attemptedto modulate high-dose 5-FU (3 g/m²) with oral leucovorin (LV)but the regimen too toxic and the dose had to be reduced. Anew phase II trial with 2 g/m²/week plus oral leucovorin wasplanned. PATIENTS AND METHODS:: From July 1992 to June 1994, 110 previously untreated patientswith advanced, measurable colorectal cancer were included ina multicenter study. The patients received, on an outpatientbasis, 5-FU 2 g/m² by continuous infusion for 48 hours oncea week until progression or the appearance of toxic effects.Oral leucovorin (60 mg every six hours) was also given duringthe 5-FU infusion. RESULTS:: Patients received a median dose intensity of 5-FU of 1.6 g/m²/week(range 0.9–2). Three complete responses and 36 partialresponses were observed. The overall response rate was 37.5%(95% CI, 28% to 46.8%), the median time to progression 7.4 monthsand median survival 14.5 months. W.H.O. grade 3 diarrhea occurredin 27 patients (24.5%); grade 3 mucositis was observed in 9(8.1%) patients and grade 4 in one. Grade 3 nausea and vomitingwas reported in 13 (11.7%) patients, while grade 3 hand-footsyndrome was detected in only 5 (4.5%). Grade 4 leukopenia occurredin one patient and grade 3–4 thrombocytopenia in two. CONCLUSION:: Oral leucovorin modulation of weekly 48-hour continuous infusionof 5-FU at 2 g/m² is an active regimen, with diarrhea and mucositisas the main limiting toxic effects. Its antitumor activity doesnot seem superior to that obtained with a weekly 48-hour continuousinfusion of 5-FU alone at a dose of 3.5 g/m². advanced colorectal cancer, biochemical modulation, continuous infusion, fluorouracil, phase II trial     

Cisplatin and protracted venous infusion 5-fluorouracil (CF) -- good symptom relief with low toxicity in advanced pancreatic carcinoma

Purpose: The combination of protracted venous infusion (PVI)5-FU with moderate dose cisplatin was evaluated in patientswith advanced pancreatic cancer Patients and methods: Sixty-three patients with locally advancedor metastatic disease were treated with cisplatin (60 mg/m²every 21 days) and PVI 5-FU (300 mg/m²/day) for a maximum of24 weeks. All patients had histologkally/ cytologically confirmedtumour. Radiological response was assessed by CT scanning andtoxicity, performance status and symptomatic response were assessed3 weekly Results: The objective response rate was 16% with two radiologicalcomplete responses. The median survival was 7.6 months witha 1-year survival of 33% and a median progression-free survivalof 6.6 months. Patients who had local disease only had a mediansurvival of 14.8 months with a 1-year survival of 52%. Thirty-fourpercent of patients had an improvement in performance statuson treatment and specific symptom response rates were weightloss 71%, dysphagia 100%, nausea and vomiting 70%, pain 60%,anorexia 50% and reflux 81%. Chemotherapy was well toleratedwith grade 3 or 4 toxicity being nausea/vomiting 5%, diarrhoea7%, infection 4%, stomatitis 2%, plantar palmar syndrome 2%,anaemia 14%, leucopenia 5%, neutro-penia 10% and thrombocytopenia8% Conclusions: The CF regimen provides good symptomatic palliationwith low toxicity in patients with advanced pancreatic cancer pancreatic cancer, 5-fluorouracil, cisplatin     

Interferon-alpha+cisplatin+5-FU therapy for gemcitabine-refractory unresectable and recurrent pancreatic cancer

Interferon-alpha (IFN-Alpha) + cisplatin (CDDP) + 5-FU therapy was given to 10 patients with gemcitabine (GEM)-refractory unresectable or recurrent pancreatic cancer. CDDP (35 mg/m(2)) was administered intravenously on the first day, IFN-Alpha (5x10(6)IU) subcutaneously on day 2,4 and 6 of each week, and 5-FU (175 mg/m(2)/day) continuously infused every day for 4 weeks. The 10 patients consisted of 8 men and 2 women with a mean age of 56.2 years. As the main site of progression, 5 patients had liver metastases, 1 had lung metastases, 2 had peritoneal dissemination, and 2 had local recurrence. The objective response rate was 30%, including 1 complete response. Grade 3 anorexia, neutropenia and thrombocytopenia occurred in 60%, 40% and 40%, respectively. IFN-Alpha + CDDP + 5-FU therapy is an effective treatment for GEM-refractory pancreatic cancer, but with moderate toxicity.     

Dose intensity and clinical response in head and neck carcinoma treated with cisplatin + 5-fluorouracil

Chemotherapy dose adjustment has been associated with cancer treatment failure in some types of cancer. The aim of this study was to evaluate the impact of dose intensity in the efficacy of neoadjuvant treatment of locally advanced squamous cell carcinoma of head and neck (SCCHN). We reviewed the records of seventy patients with locally advanced SCCHN (stage III or IV) treated with three cycles of CDDP (100 mg/m²) plus 5-day continuous infusion of 5-FU (1,000 mg/m²/day) before local therapy. Planned and received dose intensity were both calculated, and clinical response and survival were assessed. Median dose intensity received was 28.38 mg/m²/week for CDDP (range: 7.45–35) and 278.16 for 5-FU (range: 74.47–350). Overall response rate to the chemotherapy combination was 76%. Cisplatin was administered ≥75% of the planned dose in 80% of the patients, and 5-FU was administered ≥75% in 76% of cases. The response rate was significantly higher in the patients that received ≥75% of the planned dose of CDDP (82% vs 50%, p=0.004), and in patients receiving ≥75% of the planned dose of 5-FU (83% vs 53%, p=0.028). Overall survival also correlated with the dose intensity of chemotherapy. Median survival of patients receiving ≥75% of CDDP was significantly longer that patients receiving <75% of CDDP (32 vs 18 months, p=0.03). Similarly, median survival of patients receiving ≥75% of 5-FU was significantly longer that patients receiving <75% of 5-FU (33 vs 21 months, p=0.02). Maintaining a dose-intensity of CDDP and 5-FU above 75% in patients with locally advanced head and neck cancer results in an improved treatment benefit, both in terms of response rate and overall survival.     

Bolus and infusional 5-fluorouracil combined with cisplatin in advanced gastric cancer

5-Fluorouracil (5-FU) is the main drug used in the treatment of advanced gastric cancer. Combination chemotherapy is not always superior to 5-FU alone, especially when biomodulators are also administered. In an attempt to exploit all the cytotoxic mechanisms of 5-FU, we carried out a pilot study with a double route of administration of 5-FU (intravenous bolus and continuous infusion) and a multiple modulation of 5-FU by methotrexate (MTX), 6S-leucovorin (6S-LV) and cisplatin (CDDP). A group of 30 patients affected by advanced gastric cancer was treated with MTX 50 mg/m2 and 5-FU 400 mg/m2 as an i.v. bolus on day 1, followed by a 5 day i. v. continuous infusion of 5-FU 600 mg/m2/day and 6S-LV 100 mg/m2/day; on day 3 CDDP 100 mg/m2 was also administered. The regimen was repeated every 4 weeks. Six partial responses (20+/-14. 3%), 12 stable diseases (40+/-17.5%) and 12 progression (40+/-17.5%) were observed in an intent-to-treat analysis. Median survival was 7 months. All responding patients had performance status 0-1. Grade 3-4 toxicity was mainly gastrointestinal, but grade 3-4 anemia and leucopenia were also recorded. The schedule has low activity. The use of different modulators and way of administration of 5-FU does not provide advantages in advanced gastric cancer.     

Clinical Trial of Continuous Infusion of 5-Fluorouracil Using an Ambulatory Pump for Metastatic Colorectal Cancer

A clinical trial was conducted in order to evaluate the anti-tumoreffect and toxicity of a continuous ifusion of 5-fluorouracil(5-FU) for metastati colorectal cancer. Two-hundred and fiftymg/m²/day 5-FU was administered as a continuous infusion throughan indwelling central venous catheter with ambulatory pump.Twenty patients with metastatic colorectal cancer which couldbe measured or evaluated were enrolled in the trial. The objectiveresponse rate was 35% (95% confidence interval, 14–56%).The response rates by site were 33% in liver, 17% in lung, 60%in lymph nodes, 50% in adrenal gland and 50% in primary lesion.The major toxicity was stomatitis (50%; grades 2 and 3 on EasternCooperative Oncology Group (ECOG) criteria) and hand-foot syndrome(40%; grades 2 and 3 on ECOG criteria). The sequence of toxicitywas stomatitis first, followed by hand-foot syndrome. The mediancumulative dose of 5-FU from the initiation of therapy to theonset of toxicity was 7125 mg in stomatitis and 17,875 mg inhand-foot syndrome. These toxicities were mild and reversibleafter a short interruption to the 5-FU infusion. Neither hematologicaltoxicity nor serious catheter-related complications were observed.We concluded that continuous infusion of 5-FU was a feasibletreatment for the patient with metastatic colorectal cancer,and manageable on an out-patient basis     

Phase II study of carboplatin and continuous infusion bleomycin followed by cisplatin and 5-fluorouracil in recurrent head and neck cancer

BACKGROUND: Recurrent squamous cell carcinoma of the head and neck is poorlyresponsive to most chemotherapy regimens. Carboplatin and bleomycinare effective single agents with non-overlapping toxicity; therefore,we sought to explore the efficacy of this regimen in a phaseII study. In the second stage of the study, patients who didnot respond to carboplatin and bleomycin were given treatmentwith cisplatin and 5-fluorouracil (5-FU). PATIENTS AND METHODS: Patients with recurrent squamous cell carcinoma of the headand neck were treated with carboplatin 400 mg/m² followed bybleomycin 15 units intravenously as a continuous infusion for4 days. Patients with no tumor response after 3 cycles of carboplatinand bleomycin were crossed-over to receive cisplatin 100 mg/m²and 5-FU 1000 mg/m²/day continuous infusion for 5 days. RESULTS: Among the 20 carboplatin-bleomycin patients evaluable for toxicity,no cases of grade 4 granulocytopenia were reported and grade3 or 4 thrombocytopenia developed in only three patients. Threepartial responses occurred among the 19 patients (16%) [95%Cl. 0% to 32% evaluable for response to carboplatin-bleomycin.None of the 11 patients crossed-over to cisplatin and 5-FU hada major response. CONCLUSION: The combination of carboplatin and bleomycin is well toleratedin patients with recurrent head and neck cancer, but the activitydoes not appear to be superior to the activity of either agentalone. Patients who did not respond to carboplatin and bleomycinwere also resistant to the cisplatin and 5-FU regimen. head and neck cancer, chemotherapy     

A case of hepatocellular carcinoma responding to hepatic arterial infusion chemotherapy with low-dose cisplatin and 5-fluorouracil]

A 74-year-old man had multiple liver recurrence of hepatocellular carcinoma (HCC) after extended left hepatectomy. He was treated by continuous hepatic arterial infusion (HAI) chemotherapy with low-dose cisplatin (CDDP) and 5-fluorouracil (5-FU) via an implanted reservoir. A catheter was inserted percutaneously into the hepatic artery using the Seldinger technique. The patient was administered 10 mg of CDDP on day 1 and 500 mg/day of 5-FU for 4 days as one course. Four courses were administered and the PIVKA-II level decreased from 427 to 216 mAU/ml. However, infusion port problems led to interruption of chemotherapy and PIVKA-II increased to 798 mAU/ml. His chemotherapy was changed to 10 mg of CDDP on day 1 and 750 mg/day of 5-FU for 2 days. After five courses were administered, PIVKA-II decreased to 540 mAU/ml. This patient is still alive 15 months after the start of therapy. This case suggests that HAI with low-dose CDDP and 5-FU might be useful for prolonging the survival of HCC patients with a good quality of life.     

Phase II trial of PALA in combination with 5-fluorouracil in advanced pancreatic cancer

Summary Phosphonacetyl-l-aspartate (PALA), an inhibitor of aspartate transcarbamylase that depletes uridine nucleotide pools, selectively potentiates the antitumor activity of 5-fluorouracil (5-FU) in preclinical models. Due to the promising results we obtained using PALA/5-FU in colorectal cancer, we performed a phase II trial in patients presenting with advanced pancreatic cancer. PALA was given intravenously at 250 mg/m² on day 1, followed 24 h later by 2,600 mg/m² 5-FU given by 24-h infusion. Treatments were repeated weekly. A total of 41 patients who had not previously undergone chemotherapy were entered in the trial; of these, 35 were evaluable for response. Toxicity was generally mild to moderate; neurotoxicity (13/35) and diarrhea (8/35) predominated. Among the 35 patients, 1 achieved a complete response and 4, a partial remission, for an overall response rate of 14%. The median survival was 5.1 months. Pretreatment with PALA alone was not sufficient to enhance the activity of 5-FU in pancreatic cancer.Supported in part by grant CA 06927 from the National Cancer Institute     

Significance of reduction surgery for giant hepatocellular carcinoma with diffuse lung metastases and multiple intrahepatic metastases

Continuous systemic infusion of low-dose cisplatin (CDDP) (10 mg/body/day) and 5-fluorouracil (5-FU) (500 mg/body/day) was performed for advanced hepatocellular carcinoma (HCC) after hepatectomy with diffuse lung metastases and multiple intrahepatic metastases. This infusion chemotherapy, cisplatin was continued for five days, and discontinued for two days, whereas 5-fluorouracil was administered every day and repeated four weeks as one course basally. Remnant metastases had almost disappeared after systemic chemotherapy for 10 weeks. In our experience, the response rate in 13 patients who underwent reduction surgery for multiple HCC was 84.6%. Continuous infusion of low-dose CDDP/5-FU may be effective in patients having absolute non-curative resection.     

Biweekly irinotecan or raltitrexed plus 6S-leucovorin and bolus 5-fluorouracil in advanced colorectal carcinoma: a Southern Italy Cooperative Oncology Group phase II-III randomized trial.

Purpose:The aim of this randomised trial was to evaluate theactivity and toxicity of a biweekly regimen including 6S-leucovorin-modulated5-fluorouracil (LFA–5-FU), combined with either irinotecan (CPT-11 +LFA–5-FU) or raltitrexed (Tomudex®) (TOM + LFA–5-FU), inadvanced colorectal cancer patients, and to make a preliminary comparison ofboth these experimental regimens with a biweekly administration ofLFA–5-FU modulated by methotrexate (MTX + LFA–5-FU). Patients and methods:One hundred fifty-nine patients withadvanced colorectal carcinoma previously untreated for the metastatic disease(34 of them previously exposed to adjuvant 5-FU) were randomly allocated toreceive: CPT-11, 200 mg/m² i.v. on day 1, followed on day 2 by LFA,250 mg/m² i.v. infusion and 5-FU, 850 mg/m² s i.v. bolus(arm A); TOM, 3 mg/m² i.v. on day 1, followed on day 2 by LFA, 250mg/m² i.v. infusion and 5-FU, 1050 mg/m² i.v. bolus (armB); or MTX, 750 mg/m² i.v. on day 1, followed on day 2 by LFA, 250mg/m² i.v. infusion and 5-FU, 800 mg/m² i.v. bolus (armC). Courses were repeated every two weeks in all arms of the trial. Responserate (RR) was evaluated after every four courses. The sample size was definedto have an 80% power to detect a 35% RR for each experimentaltreatment, and to show a difference of at least 4% in RR with thestandard treatment if the true difference is 15% or more. Results:The RRs were: 34% (95% confidence interval(95% CI): 21%–48%) in arm A, including 3 completeresponses (CRs) and 15 partial responses (PRs), 24% (95% CI:14%–38%) in arm B, including 2 CRs and 11 PRs, and24% (95% CI: 14%–38%), with 2 CRs and 11PRs, in arm C. After a median follow-up time of 62 (range 18–108) weeks,the median time to progression was 38, 25, and 27 weeks for arm A, B, and C,respectively. With 94 patients still alive, the one-year probability ofsurvival was 61%, 54%, and 59%, respectively. WHO grade3 or 4 neutropenia and diarrhoea affected 46% and 16%,respectively, of patients treated with CPT-11 + LFA–5-FU. Medianrelative dose intensity over eight cycles (DI₈) was 78% forCPT-11 and 82% for 5-FU. Severe toxicities of TOM + LFA–5-FU wereneutropenia (16%) and diarrhoea (16%), but median relativeDI₈ was 93% for TOM, and 82% for 5-FU. Conclusions:CPT-11 + LFA–5-FU compares favorably in termof activity and toxicity with other combination regimens including CPT-11 andcontinuous infusional 5-FU. The hypothesis of a RR 15% higher than theMTX + LFA–5-FU treatment can not be ruled out after this interimanalysis. The TOM + LFA–5-FU regimen showed a RR and a toxicity profilevery close to the MTX + LFA–5-FU combination, and dose not deservefurther evaluation in advanced colorectal cancer patients.     

Biochemical modulation of 5-fluorouracil: A randomized comparison of sequential methotrexate, 5-fluorouracil and leucovorin versus sequential 5-fluorouracil and leucovorin in patients with advanced symptomatic colorectal cancer

BACKGROUND: The optimal chemotherapy for advanced colorectal carcinoma isnot known. Two regimens, both based upon biochemical modulationof 5-FU, were compared in a randomized multicenter trial. PATIENTS AND METHODS: A total of 202 symptomatic patients were randomly allocatedto receive either sequential methotrexate, 250 mg/m², duringthe first 2 hours and 5-FU, 500 mg/m², at hours 3 and 23 followedby leucovorin rescue initiated at hour 24 (15 mg x 8) (MFL)or sequential 5-FU 500 mg/m² followed by leucovorin 60 mg/m²30–40 minutes later, on days 1 and 2 (FLv). Treatmentswere repeated every 14 days for eight courses and then every3 to 4 weeks. Four patients were unevaluable. RESULTS: The two treatments were equally effective with respect to objectiveresponse rates (complete (CR) + partial (PR), MFL 17%, FLv 21%),subjective response rates (symptom relief in the absence ofsevere adverse effects, 45% vs. 37%), and survival (median 7.5vs. 9 months). All responses lasted at least 4 months. Overall,toxicity was low and comparable between the groups, but serioustoxicity was more common in the MFL group. CONCLUSIONS: Since FLv is easier to administer and carries less risk forserious toxicity, it should be recommended as a first-line treatmentbefore MFL. On either regimen, about 40% of symptomatic patientscan expect palliation, i.e., symptomatic relief without severeadverse effects, for at least 4 months. biochemical modulation, chemotherapy, colorectal cancer, 5-fluorouracil, subjective response     

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.