Combined treatment of oxaliplatin and capecitabine in patients with metastatic esophageal squamous cell cancer

AIM： To investigate the efficacy and side effects of the combined therapy of oxaliplatin and capecitabine in patients with metastatic esophageal squamous cell cancer （ESCC） and the survival of the patients. METHODS： Sixty-four patients （median age of 63 years） with histological or cytological confirmation of ESCC received oxaliplatin 120 mg/m^2 intravenously on day 1 and capecitabine 1000 mg/m^2 orally twice daily on days 1 to 14 in a 21-d treatment cycle as palliative chemotherapy. Each patient received at least two cycles of treatment. The efficacy, side effects and patient survival were evaluated. RESULTS： The partial response （PR） rate was 43.8% （28/64）. Stable disease （SD） rate was 47.9% （26/64）, and disease progression rate was 15.6% （10/64）. The clinical benefit rate （PR ＋ SD） was 84.4%. The main toxicities were leukopenia （50.0%）, nausea and vomiting （51.6%）, diarrhea （50.0%）, stomatitis （39.1%）, polyneuropathy （37.5%） and hand-foot syndrome （37.5%）. No grade 4 event in the entire cohort was found. The median progression-free survival was 4 mo, median overall survival was 10 mo （95% CI： 8.3-11.7 mo）, and the 1- and 2-year survival rates were 38.1% and 8.2%, respectively. High Karnofsky index, single metastatic lesion and response to the regimen indicated respectively good prognosis. CONCLUSION： Oxaliplatin plus capecitabine regimen is effective and tolerable in metastatic ESCC patients. The regimen has improved the survival moderately and merits further studies.     

Phase II trial of rituximab plus CVP combination chemotherapy for advanced stage marginal zone lymphoma as a first-line therapy: Consortium for Improving Survival of Lymphoma (CISL) study

We conducted a multicenter, phase II trial to investigate the efficacy and safety of rituximab plus CVP (R-CVP) combination therapy for patients with previously untreated stage III or IV marginal zone lymphoma (MZL). The treatment consisted of rituximab 375 mg/m(2), cyclophosphamide 750 mg/m(2) and vincristine 1.4 mg/m(2) (maximum 2.0 mg) being given intravenously on day 1 and oral prednisolone 100 mg on days 1-5. The treatment was repeated every 3 weeks and this was continued for six or eight cycles. Forty-two patients were enrolled from 13 institutes in Korea. Among them, two patients were dropped after the first and second cycles of chemotherapy, respectively, without evaluation. The 40 patients received a total of 287 cycles of R-CVP chemotherapy. The overall response rate was 88% (95% CI, 77-98%) with 24 complete responses (60%). The median duration of response was 28.3 months. After a median follow-up of 38.2 months, the estimated 3-year progression-free survival and overall survival were 59% and 95%, respectively. There were 30/287 cycles (11%) and 5/287 cycles (2%) of grade 3 or 4 neutropenia and febrile neutropenia, respectively. The R-CVP regimen can be an effective and tolerable first-line immunochemotherapy regimen for advanced stage MZL.     

A phase II study of gemcitabine and cisplatin in patients with advanced hepatocellular carcinoma.

The primary objective of this study was to determine the response rates of a combination of gemcitabine and cisplatin in unresectable hepatocellular carcinoma (HCC) in Indian patients. The secondary objectives were to evaluate the toxicity, time to progressive disease and overall survival for this combination. Chemonaive patients with histopathologically proven, bidimensionally measurable, stage Ill or IV unresectable HCC were enrolled into this study. All the patients were required to have a Zubrod's performance status not greater than 2, should not have undergone prior radiotherapy and were required to have adequate major organ function. Patients received gemcitabine (1250 mg/m2 intravenously over 30 to 60 min) on days 1 and 8, and cisplatin (70 mg/m2 intravenously over 2 hours) on day land every 21 days. Response assessment was done by a Computed Tomography scan after every two cycles of chemotherapy. From May to December 1999, 30 patients were enrolled in the study; they were all eligible for efficacy and toxicity analysis. Six (20%) patients achieved a partial response and 13 (43%) patients demonstrated stable disease with 11 (37%) patients showing disease progression. The median time to progression was 18 weeks (range 1 to 74 weeks) and the median duration of response was 13 weeks (range 4 to 68 weeks). The 1-year survival rate was 27% and the median overall survival was 21 weeks (95% CI: 17 to 43 weeks). WHO grade 3 and 4 anemia was seen in 11 (37%) and 2 (7%) patients, respectively. Four (13%) patients each experienced grade 3 and 4 neutropenia and grade 3 and 4 thrombocytopenia was seen in 2 (7%) patients each. Major, non-hematologic toxicities were grade 4 elevated bilirubin levels and grade 3 oral toxicity, in 1 patient (3%) each. This regimen was well tolerated and did show activity in Indian patients with advanced unresectable HCC. There is a need to further evaluate this combination in order to define its role in the treatment of HCC.     

Oral Xeloda plus bi-platinu two-way combined chemotherapy in treatment of advanced gastrointestinal malignancies

AIM: To compare the effect, adverse events, cost-effectiveness and dose intensity (DI) of oral Xeloda vs calcium folinate (CF)/5-FU combination chemotherapy in patients with advanced gastrointestinal malignancies, both combined with bi-platinu two-way chemotherapy. METHODS: A total of 131 patients were enrolled and randomly selected to receive either oral Xeloda (X group) or CF/5-FU (control group). Oral Xeloda 1 000 mg/m2 was administered twice daily from d 1 to 14 in X group, while CF 200 mg/m2 was taken as a 2-h intravenous infusion followed by 5-FU 600 mg/m2 intravenously for 4-6 h on d 1-5 in control group. Cisplatin and oxaliplatin were administered in the same way to both the groups: cisplatin 60-80 mg/m2 by hyperthermic intraperitoneal administration, and oxaliplatin 130 mg/m2 intravenously for 2 h on d 1. All the drugs were recycled every 21 d, with at least two cycles. Pyridoxine 50 mg was given t.i.d. orally for prophylaxis of the hand-foot syndrome (HFS). Then the effect, adverse events, cost-effectiveness and DI of the two groups were evaluated. RESULTS: Hundred and fourteen cases (87.0%) finished more than two chemotherapy cycles. The overall response rate of them was 52.5% (X group) and 42.4% (control group) respectively. Tumor progression time (TTP) was 7.35 mo vs 5.95 mo, and 1-year survival rate was 53.1% vs 44.5%. There was a remarkable statistical significance of TTP and 1-year survival between the two groups. The main Xeloda-related adverse events were myelosuppression, gastrointestinal toxicity, neurotoxicity and HFS, which were mild and well tolerable. Therefore, no patients withdrew from the study due to side effects before two chemotherapy cycles were finished. Both groups finished pre-arranged DI and the relative DI was nearly 1.0. The average cost for 1 patient in one cycle was Y9 137.35 (X group) and Y8 961.72 (control group), or US $1100.89 in X group and $1 079.73 in control group. To add 1% to the response rate costs ￥161.44 vs ￥210.37 respectively (US $19.45 vs $25.35). One-month prolongation of TTP costs ￥1 243.18 vs ￥1506.17 (US $149.78 vs $181.47). Escalation of 1% of 1-year survival costs ￥172.74 vs ￥201.64 (US $20.75 vs $24.29). CONCLUSION: Oral Xeloda combined with bi-platinu two-way combination chemotherapy is efficient and tolerable for patients with advanced gastrointestinal malignancies; meanwhile the expenditure is similar to that of CF/5-FU combined with bi-platinu chemotherapy, and will be cheaper if we are concerned about the increase of the response rate, TTP or 1-year-survival rate pharmacoeconomically.     

Systemic gemcitabine combined with intra-arterial low-dose cisplatin and 5-fluorouracil for advanced hepatocellular carcinoma： Seven cases

The combination of intra-arterial low-dose cisplatin and 5-fluorouracil （5-FU） is effective against advanced hepatocellular carcinoma （HCC）. Systemic gemcitabine chemotherapy seems effective in many cancers. We report the results of combination therapy with systemic gemcitabine, intra-arterial low-dose cisplatin and 5-FU （GEMFP）. Seven patients with non-resectable advanced HCC were treated with GEMFP. One course of chemotherapy consisted of daily intra-arterial cisplatin （20 mg/body weight/hour on d 1, 10 mg/body weight per 0.5 h on d 2-5 and 8-12）, followed by 5-FU （250 mg/body weight per 5 h on d 1-5 and 8-12） via an injection port. Gemcitabine at 1000 mg/m2 was administered intravenously at 0.5 h on d 1 and 8. The objective response was 57%. The response to GEMFP was as follows： complete response （no patients）, partial response （four patients）, stable disease （three patients）, and progressive disease （no patients）. The median survival period was 8 mo （range, 5-55）. With regard to the National Cancer Institute Common Toxicity Criteria （NCI-CTC） grade 3 or 4 adverse reactions, seven （100%）, seven, six （86%） and one （14%） patients developed leukopenia, neutropenia, thrombocytopenia and anemia, respectively. GEMFP may potentially be effective for non- resectable advanced HCC, but it has severe hematologic toxicity.     

替吉奥联合紫杉醇周疗对晚期老年胃癌患者的临床疗效评价

目的评价替吉奥(S-1)联合紫杉醇周疗治疗晚期老年胃癌患者的近期疗效及毒副反应物。方法将广西横县人民医院确诊的38例晚期老年胃癌患者随机分为2组,治疗组20例,采用紫杉醇联合替吉奥化疗:紫杉醇60 mg/m2,第1、8、15 d用药,替吉奥胶囊80 mg/m2,2次/d,连续口服14 d,28 d为1个周期;对照组18例,采用FP方案:顺铂15 mg/m2,第1~5天静点,5-Fu 750mg/m2,第1~5天静点,28 d为1个周期。两组患者至少治疗2个周期后评价其疗效及毒副反应。结果治疗组与对照组的有效率(RR)、疾病控制率(DCR)、1年生存率分别为40.0%、75.0%、55.0%和22.2%、50.0%、38.9%,差异无统计学意义(P0.05);治疗组患者KPS改善情况优于对照组(P0.05);治疗组的胃肠道反应及Ⅲ~Ⅳ度骨髓抑制明显低于对照组(P0.05)。结论替吉奥口服联合紫杉醇周疗方案化疗有效率高,老年患者耐受性好,是老年晚期胃癌患者值得选择的化疗方案。     

Esophagectomy for locally advanced esophageal cancer, followed by chemoradiotherapy and adjuvant chemotherapy

AIM: To compare the efficacy and toxicity of a three-step combination therapy with post-operative radiation alone for locally advanced esophageal cancer. METHODS: Patients with T3-4 and NO-1 esophageal carcinoma from a number of institutions were non-randomly, prospectively enrolled in the study. All patients underwent single-stage curative en bloc esophagectomy. The patients were then assigned into one of two treatment groups based on treatment consisting of either post-operative concurrent chemoradiotherapy (CCRT) with weekly cisplatin 30 mg/m~2 followed by systemic adjuvant chemotherapy (four monthly cycles of cisplatin 20 mg/m~2 and 5-fluorouracil 1000 mg/m~2 for five consecutive days), or, post-operative radiation alone. The radiotherapy dose was 55-60 Gy for all patients. Primary end-point of this study was to assess the per-protocol patients' improvement of overall survival benefit. Secondary end-point was designed to evaluate both the per-protocol and intent-totreat patients' outcome of survival. RESULTS: A total of 60 patients (n=30 per group) were enrolled in this study. The two groups were generally comparable for demographic characteristics and hematologicai and non-hematological toxicities. The CCRT with weekly cisplatin was well tolerated, with significantly better overall survival (30.9 mo vs 20.7 mo; 95% CI, 27.5-36.4 vs 15.2-26.1) and 3-year survival (70.0% vs 33.7%; P=0.003). Low histological grade of tumor (P<0.001) was associated with favorable survival in these locally advanced patients. CONCLUSION: For locally advanced esophageal cancer, the combination of esophagectomy, post-operative CCRT with weekly cisplatin and systemic adjuvant chemotherapy is well tolerated and effective. A large-scale, prospective randomized trial of this regimen is in progress.     

甲孕酮联合IEP与单用IEP方案治疗非小细胞肺癌的对比研究

目的 比较甲孕酮联合IEP方案与单用IEP方案治疗晚期非小细胞肺癌的疗效及毒副作用。方法：54例晚期非小细胞肺癌患随机分成两组,联合组：口服甲孕酮600mg／天,IFO1．5mg/m^2静脉滴注第1－5天,EP15mg/m^2持续深静脉滴注第1－5天,PDD15mg/m^2静脉滴注第1－5天;单化疗组：同上IEP方案。两组均以每28天为一周期,至少重复3个周期。结果：联合组有效率（CR＋PR）：48．1％,单化组有效率（CR＋PR）：44．4％,P＞0．05;中位生存期：联合组36周,单化组30周,P＜0．01;骨髓抑制、恶性呕吐等反应联合组均较单化组轻,P＜0．01;体重：用药12周后,联合组平均增加2．75kg,单化组平均减轻1．85kg,P＜0．05。结论：甲孕酮联合IEP方案与单化IEP方案治疗晚期非小细胞肺癌有效率无明显差异,但前中位生存期长,毒副反应轻,患生活质量明显提高。     

Sirolimus, bevacizumab, 5-Fluorouracil and irinotecan for advanced colorectal cancer： A pilot study

AIM： To evaluate the efficacy and the safety of combined 5-Fluorouracil, irinotecan, bevacizumab and sirolimus in refractory advanced colorectal carcinoma. METHODS： We initiated a regimen with at day 1 an injection （iv） of bevacizumab at 5 mg/kg, followed by 180 mg/m^2 irinotecan, followed by Leucovorin 400 mg/m^2, followed by a 5-Fluorouracil bolus 400 mg/m^2 and a 46-h infusion 2400 mg/m^2. Sirolimus was given orally as continuous administration of 2 mg twice a day every days. This treatment was repeated every 14 d. RESULTS： A total of 12 patients were enrolled. All patients presented with metastatic disease that had failed at least three lines of chemotherapy that contained oxaliplatin, irinotecan and bevacizumab. Cetuximab failure was also observed in all K-Ras wildtype patients. The median number of cycles was 8.5 （range 2-20） and clinical benefit was observed in eight patients. The median time to progression was 5 mo and the median survival was 8 too. Grade 3 neutropenia developed in four patients, and grade 3 diarrhea and stomatitis in two.CONCLUSION： The combination regimen of 5-Fluorouracil,irinotecan, bevacizumab and sirolimus in advanced colorectal carcinoma after failure of dassical be.absent is feasible and promising. Further evaluation of this combination is required.     

FOLFIRI plus bevacizumab as a second-line therapy for metastatic intrahepatic cholangiocarcinoma

AIM:To evaluate the efficacy and tolerance of FOLFIRI plus bevacizumab treatment outcome as second-line treatment for metastatic intrahepatic cholangiocarcinoma.METHODS:Thirteen consecutive patients with metastatic intrahepatic cholangiocarcinoma who were refractory tofirst-line therapy consisting of gemcitabine plus oxaliplatinbased first-line chemotherapy given intravenously via intra-arterial infusion were treated with FOLFIRI[irinotecan(180 mg/m2 i.v.over 90 min)concurrently with folinic acid(400 mg/m2 i.v.over 120 min)followed by fluorouracil(400 mg/m2 i.v.bolus)then fluorouracil 2400 mg/m2 intravenous infusion over 46 h]and bevacizumab(5mg/kg)every 2 wk.Tumor response was evaluated by computed tomography scan every 4 cycles.RESULTS:The best tumor responses using response evaluation criteria in solid tumor criteria were:complete response for 1 patient,partial response for 4 patients,and stable disease for 6 patients after 6 mo of follow-up.The response rate was 38.4%(95%CI:12.5-89)and the disease control rate was 84.5%(95%CI:42-100).Seven deaths occurred at the time of analysis,progression free survival was 8 mo(95%CI:7-16),and median overall survival was 20 mo(95%CI:8-48).No grade 4toxic events were observed.Four grade 3 hematological toxicities and one grade 3 digestive toxicity occurred.An adaptive reduction in chemotherapy dosage was required in 2 patients due to hematological toxicity,and a delay in chemotherapy cycles was required for 3 patients.CONCLUSION:FOLFIRI plus bevacizumab combination treatment showed promising efficacy and safety as second-line treatment for metastatic intrahepatic cholangiocarcinoma after failure of the first-line treatment of gemcitabine plus oxaliplatin chemotherapy.     

Pilot study of postoperative adjuvant chemoradiation for advanced gastric cancer： Adjuvant 5-FU/cisplatin and chemoradiation with capecitabine

AIM:To evaluate the efficacy and toxicity of postopera-tive chemoradiation using FP chemotherapy and oralcapecitabine during radiation for advanced gastric cancerfollowing curative resection.METHODS:Thirty-one patients who had underwent apotentially curative resection for Stage Ⅲ and Ⅳ(MO)gastric cancer were enrolled.Therapy consists of onecycle of FP(continuous infusion of 5-FU 1000 mg/m~2on d 1 to 5 and cisplatin 60 mg/m~2 on d 1)followed by4500 cGy(180 cGy/d)with capecitabine(1650 mg/m~2daily throughout radiotherapy).Four wk after completionof the radiotherapy,patients received three additionalcycles of FP every three wk.The median follow-up dura-tion was 22.2 mo.RESULTS:The 3-year disease free and overall survivalin this study were 82.7% and 83.4%,respectively.Fourpatients(12.9%)showed relapse during follow-up.Eightpatients did not complete all planned adjuvant therapy.Grade 3/4 toxicities included neutropenia in 50.2%,ane-mia in 12.9%,thrombocytopenia in 3.2% and nausea/vomiting in 3.2%.Neither grade 3/4 hand foot syndromenor treatment related febrile neutropenia or death wereobserved.CONCLUSION:These preliminary results suggest thatthis postoperative adjuvant chemoradiation regimen ofFP before and after capecitabine and concurrent radio-therapy appears well tolerated and offers a comparable toxicity profile to the chemoradiation regimen utilized inINT-0116.This treatment modality allowed successfulloco-regional control rate and 3-year overall survival.     

S-1 plus gemcitabine chemotherapy followed by concurrent radiotherapy and maintenance therapy with S-1 for unresectable pancreatic cancer

AIM: To investigate the feasibility and efficacy of the combination of S-1 with gemcitabine followed by oral S-1 with concurrent radiotherapy (intensity modulated radiotherapy, IMRT) and maintenance therapy with S-1 for locally advanced pancreatic cancer.METHODS: Subjects selected in the study were patients who had unresectable and locally advanced pancreatic cancer without distant metastases, adequate organ and marrow functions, an Eastern Cooperative Oncology Group performance status of 0-1 and no prior anticancer therapy. Initially the subjects received two cycles of chemotherapy, oral administration of S-1 40 mg/m² twice daily from day 1 to day 14 of a 21-d cycle, with 30-min intravenous infusions of gemcitabine 1000 mg/m² on day 1 and day 8. Two weeks after the completion of chemotherapy, S-1 was administered orally with concurrent IMRT. Oral S-1 was administered at a dose of 80 mg/m² per day twice daily from day 1 to day 14 and from day 22 to day 35. Radiation was concurrently delivered at a dose of 50.4 Gy (1.8 Gy/d, 5 times per week, 28 fractions). One month after the completion of chemotherapy and radiotherapy, S-1 was administered orally at a dose of 80 mg/m² per day twice daily for 14 d, followed by a 14-d rest period. This cycle was repeated as maintenance therapy, until unacceptable toxicity occurred or the disease worsened. Thirty-two patients were involved in this study. The median follow-up was 15.6 mo (range: 8.6-32.3 mo).RESULTS: Thirty-two patients completed the scheduled course of chemotherapy, while 30 patients (93.8%) received chemoradiotherapy with two patients ceasing to continue with radiotherapy. The major toxic effects were nausea and leukopenia. There was no grade 4 toxicity or treatment-related death. According to the Response Evaluation Criteria in Solid Tumors criteria, the objective tumor response was partial response in 17 (53.1%) patients, stable disease in 9 (28.1%), and progressive disease in 6 (18.8%). The median overall survival and median progression-free survival were 15.2 mo and 9.3 mo, respectively. The survival rates at 1 year and 2 years were 75% and 34.4%, respectively.CONCLUSION: The combination of S-1 with gemcitabine followed by oral S-1 with IMRT and maintenance therapy with S-1 alone in patients with locally advanced pancreatic cancer may be considered a well-tolerated, promising treatment regimen.     

ADOC regimen for unresectable advanced thymic cancer]

Between 1996 and 1998, we treated 6 patients with unresectable and advanced thymic cancer (stages IVa and IVb). All received 50 mg/m2 of cisplatin and 40 mg/m2 of doxorubicin intravenously (i.v.) on day 1,0.6 mg/m2 of vincristine i.v. on day 3, and 700 mg/m2 of cyclophosphamide i.v. on day 4; ADOC regimen, respectively at 3-4 week intervals. Four patients obtained a partial response (PR) after ADOC chemotherapy and the overall clinical response rate was 67%. No life-threatening side effects were noted. In 2 patients, cisplatin plus VP-16 chemotherapy failed to demonstrate any benefits prior to the ADOC regimen. Radiotherapy was initiated after the achievement of PR in the other 2 patients. ADOC chemotherapy appears to be an effective treatment for thymic cancer.     

Fludarabine plus cyclophosphamide versus fludarabine alone in first-line therapy of younger patients with chronic lymphocytic leukemia

Combination chemotherapy with fludarabine plus cyclophosphamide (FC) was compared with the standard regimen of fludarabine monotherapy in first-line treatment of younger patients with chronic lymphocytic leukemia (CLL). Between 1999 and 2003, a total of 375 patients younger than 66 years who predominantly had advanced CLL were randomly assigned to receive either fludarabine (25 mg/m(2) for 5 days intravenously, repeated every 28 days) or FC combination therapy (fludarabine 30 mg/m(2) plus cyclophosphamide 250 mg/m(2) for 3 days intravenously, repeated every 28 days). Both regimens were administered to a maximum of 6 courses. FC combination chemotherapy resulted in significantly higher complete remission rate (24%) and overall response rate (94%) compared with fludarabine alone (7% and 83%; P < .001 and P = .001). FC treatment also resulted in longer median progression-free survival (48 vs 20 months; P = .001) and longer treatment-free survival (37 vs 25 months; P < .001). Thus far, no difference in median overall survival has been observed. FC caused significantly more thrombocytopenia and leukocytopenia but did not increase the number of severe infections. In summary, first-line treatment with FC increases the response rates and the treatment-free interval in younger patients with advanced CLL.     

A randomized comparison of postremission therapy in acute myelogenous leukemia: a Southeastern Cancer Study Group trial

The Southeastern Cancer Study Group conducted a post-remission induction randomized trial in adult acute myelogenous leukemia to assess the efficacy of alternate drug therapy during consolidation and of immunotherapy during maintenance. Of 508 evaluable patients entered into the study, 335 (66%) achieved a complete remission treated with a 7-day infusion of cytosine arabinoside at a dose of 100 mg/sq m/day and 3 days of daunorubicin at a dose of 45 mg/sq m/day. Those in remission were randomized to receive 3 courses of 1 of 3 consolidation regimens: (A) a continuous infusion of 5-azacytidine, 150 mg/sq m/day for 5 days; (B) 5-azacytidine plus beta-deoxythioguanosine, 300 mg/sq m/day for 5 days; or (C) cytosine arabinoside, 100 mg/sq m/day intravenously, and thioguanine, 100 mg/sq m orally every 12 hr, plus daunorubicin, 10 mg/sq m every 24 hr daily for 5 days. There was no difference in relapse rate among the 3 arms. Those completing consolidation and remaining in remission were randomized to 1 of 3 maintenance regimens: (D) chemotherapy, 5-day infusion of cytosine arabinoside and 2 days of daunorubicin (same doses as induction) given every 13 wk for 1 yr; (E) BCG given twice weekly for 1 mo and then monthly for 1 yr; or (F) the combination of regimens D and E. The median duration of remission was significantly better on regimen D (17.4 versus 9.4 and 9.5 mo), and median survival was 29 mo compared to 21 mo for the other regimens. Those given different drugs during consolidation than used for induction (regimens A and B) and subsequent chemotherapy for maintenance (regimen D) had the longest remission durations and survival. Immunotherapy was not as good as intensive chemotherapy for maintenance.     

卡培他滨联合奥沙利铂治疗老年性胃癌

目的 评价卡培他滨联合奥沙利铂方案治疗老年性胃癌的疗效及不良反应.方法 将2003年1月至2006年12月78例老年性胃癌患者随机分为治疗组(卡培他滨联合奥沙利铂)及对照组(5-Fu联合奥沙利铂及亚叶酸钙),每组39例.治疗组奥沙利铂130 mg/m2静脉滴注2h,第1天口服希罗达化疗2 000 mg/m2,每天分2次...     

A phase II study of combination chemotherapy with gemcitabine, 5-fluorouracil, and cisplatin for advanced pancreatic cancer]

BACKGROUND/AIMS: Gemcitabine has been the standard regimen for advanced pancreatic cancer, but the effect on the response rate and survival is still disappointing, leading to many trials of combination chemotherapy. 5-FU and cisplatin were combined with gemcitabine in this trial, as they are synergistic with gemcitabine and each other as well. This study was aimed to assess the effectiveness and safety of combination chemotherapy with gemcitabine, 5-FU, and cisplatin for advanced pancreatic cancer. METHODS: Patients with advanced pancreatic cancer were entered into this study. Gemcitabine at a dose of 800 mg/m2 on day 1 and 8, 5-FU 1,000 mg/m2/day from day 1 to 3 for 72 hours, and cisplatin 60 mg/m2 on day 2, 24 hours after the start of gemcitabine were administered every 3 weeks. RESULTS: From December 2001 to January 2004, twenty patients were enrolled in this study. Among 17 of these patients assessable, 3 patients had a partial remission with the response rate of 23.6% (95% confidence interval, 6.2-41.0%). The median time to disease progression was 230 days and median duration of survival was 322 days. Among total of 91 cycles, leukopenia, neutropenia, and thrombocytopenia of grade 3 or 4 occurred in 12 cycles (13.2%), 12 cycles (13.2%), and 23 cycles (24.4%), respectively. Grade 3 or 4 mucositis developed at 2 cycles (2.2%), and nausea and vomiting were encountered in 3 cycles (3.3%). CONCLUSIONS: Combination chemotherapy with gemcitabine, 5-FU, and cisplatin for advanced pancreatic cancer is active and well-tolerated, warranting a phase III study.     

Phase II study of gemcitabine and cisplatin in advanced biliary tract cancer

BACKGROUND: The aim of this phase II study was to determine the efficacy of gemcitabine plus cisplatin chemotherapy in patients with advanced biliary tract cancer. METHODS: Eligibility criteria included histologically confirmed adenocarcinoma with measurable tumor in the biliary tract that was unresectable and either locally advanced or metastatic. Patients received a combination of gemcitabine (1000 mg/m(2) intravenously [IV] on days 1, 8, and 15) and cisplatin (75 mg/m(2) IV on day 1). Cycles were repeated every 28 days. Objective tumor response rates and toxicities were evaluated according to World Health Organization criteria. RESULTS: Twenty-seven patients were enrolled in the study and a total of 120 cycles of chemotherapy were administrated. Objective partial response was observed in nine (33.3%) patients, while stable disease was found in seven (25.9%) patients. The median survival time was 10.0 months and the 1-year survival rate was 36%. Median time to disease progression was 5.6 months. The most common grade 3-4 toxicities were leukopenia (25.9%), anemia (29.6%), thrombocytopenia (22.2%), and vomiting (18.5%). Only one patient was hospitalized for chemotherapy-related complications. CONCLUSION: Gemcitabine and cisplatin combination chemotherapy is an effective, safe, and well-tolerated regimen for the treatment of advanced biliary tract cancer.     

Deoxycoformycin-containing combination chemotherapy for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group Study (JCOG9109)

Aggressive adult T-cell leukemia-lymphoma (ATL) generally has a very poor prognosis. Deoxycoformycin (DCF, pentostatin), an inhibitor of adenosine deaminase, has shown promising therapeutic efficacy for ATL. To develop a new effective therapy against aggressive ATL, we carried out a multicenter phase II study of DCF-containing combination chemotherapy. Sixty-two previously untreated patients with ATL (34, 21, and 7 patients with diseases of the acute, lymphoma, and unfavorable chronic types, respectively) were enrolled, but 2 were ineligible because they were judged to be favorable chronic types. A regimen of 1 mg/m2 vincristine intravenously on days 1 and 8, 40 mg/m2 doxorubicin intravenously on day 1, 100 mg/m2 etoposide intravenously on days 1 through 3, 40 mg/m2 prednisolone orally on days 1 and 2, and 5 mg/m2 DCF intravenously on days 8, 15, and 22 was administered every 28 days for 10 cycles unless disease progression or toxic complications occurred. Fifty-two percent of 60 eligible patients responded (95% confidence interval [CI], 38%-65%), with 17 patients (28%) achieving a complete response (CR) (95% CI, 17%-41%) and 14 achieving a partial response. The CR rate was inferior to those of both the previous Japan Clinical Oncology Group (JCOG) study (JCOG8701, 43%), a 9-drug combination chemotherapy of the second generation, and the subsequent JCOG9303 study (35%), a granulocyte colony-stimulating factor-supported, dose-intensified, 9-drug regimen. The median survival time of the 60 eligible patients in JCOG9109 was 7.4 months, and the estimated 2-year survival rate was 15.5%; these results were identical with those of JCOG8701 but inferior to those of JCOG9303. Grade 4 neutropenia and infection of grade 3 or greater were frequent (67% and 22%, respectively), and treatment-related death was observed in 4 patients (7%), septicemia in 2, and cytomegalovirus pneumonia in 2. We conclude that DCF-containing combination chemotherapy is not a promising regimen against aggressive ATL.     

5-FU,folinic acid and cisplatin (LV5FU2-P) for unresectable pancreatic cancer

AIM: To prospectively evaluate efficacy and tolerance of the 5-fluorouracil + folinic acid + cisplatin (LV5FU2-P) combination in the treatment of unresectable pancreatic carcinoma. PATIENTS AND METHODS: Between March 1998 and June 2000, 35 patients, mean age 61 years (37-75), with advanced (n=2) or metastatic (n=33) pancreatic cancer and initial performance status (WHO) of 0 (n=9), 1 (n=14) or 2 (n=12) were enrolled in the study. Two consecutive groups of patients were treated twice monthly, the first group (n=19) received the LV5FU2 regimen: a 2 hour-infusion of leucovorin 200 mg/m(2), 5-FU bolus 400 mg/m(2), followed by 22-hour continuous infusion of 5-FU 600 mg/m(2) on 2 consecutive days and cisplatin 50 mg/m(2) on day 2. The second group (n=16) received a simplified schedule with bolus leucovorin 40 mg/m(2), 5-FU bolus 400 mg/m(2) on day 1, followed by 5-FU 2400 mg/m(2) 48-hour infusion and cisplatin 50 mg/m(2) on day 2. Clinical symptoms and performance status were monitored together with weight changes. Tumor assessment was performed every 2 months. RESULTS: Three patients (9%) exhibited grade 4 neutropenia and grade 3 toxicity occurred in 31% of the patients (neutropenia: n=3, thrombocytopenia: n=1, vomiting: n=3, mucositis: n=3, diarrhea: n=1). There were no treatment-related deaths. Objective response was observed in 10 patients (29%, 95% confidence interval: 20-40%) including one complete response. Median progression-free survival and overall survival were 4.5 and 9 months, respectively. Six-months and 1-year survival rates were 70% and 25%, respectively. Weight gain was observed in 40% of the patients and performance status improved in 50%. CONCLUSION: LV5FU2-P regimen is active and well tolerated. It should be compared to gemcitabine as a first line therapy in advanced and metastatic pancreatic cancer.