Concurrent chemoradiotherapy with low-dose cisplatin plus 5-fluorouracil for the treatment of patients with unresectable head and neck cancer

OBJECTIVE: The purpose of this study was to determine the efficacy of concurrent chemoradiotherapy using conventional radiotherapy combined with low-dose daily 5-fluorouracil (5FU) and cisplatin (CDDP) for the locally unresectable head and neck cancer patients. PATIENTS AND METHODS: From September 1996 through December 2000, we carried out a phase II study of concurrent chemoradiotherapy with low-dose CDDP plus 5FU for the treatment of patients with unresectable squamous cell carcinoma of the head and neck. Chemoradiotherapy consisted of irradiation with 1.6-2.0 Gy/day for 5 days per week up to a total dose 68 Gy and CDDP 3 mg/m2 by intravenous infusion over 1 h plus 5FU 150 mg/m2 by intravenous infusion over 24 h per day for 5 days per week. RESULTS: Ninety percent of the patients had stage IV disease, including 65% of patients with T4 disease. Thirty-three patients (83%) received the full treatment as planned; 39 (98%) received full-dose radiotherapy and 33 (83%) full-dose chemotherapy. Of the 40 patients evaluable for response, 20 (50%) achieved complete response (CR) and 12 (30%) partial response with an overall response rate of 80%. Among the 20 CR patients, 15 underwent endoscopic blind biopsies and 4 had positive lesions. The most frequently observed toxicity was mucositis. Ten patients developed grade III mucositis, and 3 patients required enteral nutritional support through a feeding tube. Grade III leukopenia, anemia and thrombocytopenia were observed in 28, 25 and 20% of the patients, respectively. The median duration of follow-up at the time of analysis was 18 months. The median survival time was 23 months. The responders survived longer (34 months) than the nonresponders (4 months; p < 0.05). CONCLUSION: This regimen is safe and efficacious in the treatment of patients with advanced unresectable head and neck cancer.     

Concurrent chemoradiotherapy for esophageal cancer: comparison between intermittent standard-dose cisplatin with 5-fluorouracil and daily low-dose cisplatin with continuous infusion of 5-fluorouracil

Background Although current standard treatment for advanced esophageal cancer is intermittent standard-dose cisplatin with 5-fluorouracil (5-FU) (ISD-FP), daily low-dose cisplatin with continuous infusion of 5-FU (CLD-FP) is advocated for equivalent effectiveness and lower toxicity. The feasibility of these two concurrent chemoradiotherapeutic protocols was retrospectively reviewed for local control rate, overall survival, toxicity, and compliance in a single institutional situation.Methods Concurrent chemoradiotherapy, using 60Gy of radiation and ISD-FP or CLD-FP was non-randomly scheduled for 29 patients between June 1994 and March 2001.Results Complete response in the irradiated volume at the end of primary treatment was shown by 8 of 15 and 9 of 14 patients in the ISD-FP and CLD-FP groups, respectively. The projected overall survival rate at 2 years was 55% for stage III patients and 13% for stage IV. Median survival times were 14 months versus 15 months in the ISD-FP and CLD-FP groups, with no significant difference. Toxicities were similar, including two treatment-related deaths in each group. Chemotherapy was completed for 10 of 15 and 11 of 14 patients in the ISD-FP and CLD-FP groups, respectively. Modification of the planned regimen was more often required for the CLD-FP group.Conclusion CLD-FP therapy has no apparent advantage over ISD-FP therapy from the perspective of compliance and safety. A randomized phase II clinical trial comparing ISD-FP and CLD-FP, currently being performed, is expected to provide further information.     

Host immunity in colorectal cancer patients treated with low-dose Leucovorin plus 5-fluorouracil

In colorectal cancer, low-dose Leucovorin plus 5-FU therapy does not induce any severe adverse effects, and patients could receive this therapy for many cycles. The aim of this study was to investigate the relationship between host immunity and this regimen. Seven patients were enrolled in this study. Host immunity was investigated before and after chemotherapy. The ratio of Th1/Th2, PHA response, serum IAP level and the productions of IL-6, IL-10 and soluble IL-2 receptor did not change significantly before and after chemotherapy. Since low-dose Leucovorin plus 5-FU therapy might not influence host immunity, patients could receive the therapy for a long duration without toxicity.     

Pre-operative chemoradiation therapy with 5-fluorouracil and low-dose daily cisplatin for esophageal cancer: a preliminary report

BACKGROUND: A combination of chemotherapy and radiotherapy (chemoradiation therapy; CRT) has recently been developed to improve the survival of esophageal cancer patients. However, the optimal choice of chemotherapeutic agents and their doses, as well as chemotherapy and radiotherapy regimens, remain unclear. METHODS: Based on recent advances in knowledge on the radiosensitizing and biochemical modulation effects of chemotherapeutic agents, we have recently developed concurrent CRT which consisted of continuous 5-fluorouracil (5FU) administration (600 mg/m2/day, days 1-5) combined with a low dose of daily cisplatin administration (10 mg/m2/day, days 1-5, and 5 or 10 mg/m2/day, days 8-12 and 15-19) before each fraction of radiation (2 Gy each). To evaluate the efficacy and safety of our concurrent CRT, 10 esophageal cancer patients received one or one and a half courses of the CRT. RESULTS: All patients tolerated and completed a full course of the CRT. The effectiveness of the CRT on the primary tumor included pathologically or endoscopically complete responses in three patients (30%), partial response in five (50%), no response in two (20%) and tumoral downstaging (T-classification) in five (50%). Grade 2 and Grade 3 toxicity, seen in six patients, did not affect surgical operation. No patients showed CRT-related deaths. Eight patients (80%) underwent resection with no operative mortality. Of these, two patients (25%) showed pathologically or endoscopically complete responses, and four (50%) showed partial response. Three patients died of cancer after resection. The two inoperable patients showed a pathologically complete response and partial response, respectively. They were relieved of their cancer-related complaints and were living without hospitalization at the time of this analysis. CONCLUSIONS: These results suggest that the concurrent CRT based on the theoretical backgrounds is effective and has acceptable toxicities with maintaining its efficacy for the treatment of esophageal cancer patients.     

食管癌患者同期放化疗顺铂加氟尿嘧啶方案Ⅱ期临床试验

背景与目的：国外已有研究表明,同期放化疗是局部晚期食管癌的标准治疗方案,但国内文献报道同期放化疗的疗效不尽相同,同期放化疗能否提高生存率尚无定论。本研究目的是评价PF方案同期放化疗对食管癌的疗效,并观察毒性。方法：44例食管鳞癌患者随机分为同期放化疗组（简称同期组）和后程加速超分割组（简称后超组）。同期组22例,全程常规分割照射,每天一次,每次2．0Gy,每周5次,25分割,总剂量50Gy。于放疗的第1天开始化疗：顺铂52．5mg／m^2 d1,氟尿嘧啶700mg／m^2 d1-d5,每28d重复,共4周期。后超组22例：总剂量60Gv,前半程30Gv同放化疗组,3周完成;后半程30Gv加速超分割照射,每日2次,间隔至少6h,每次1．5Gy,每周10次,2周完成。结果：同期组有效率高于后超组,分别为95．5％和86．4％,但差异无统计学意义（P=0．607）。同期组2年局控率和2年生存率分别为72．2％和56．7％,后超组分别为39．0％和31．6％。同期组获得了更高的局控率和生存率,但只有局控率差异有统计学意义（P=0．014）。两组的主要急性反应为放射性食管炎、放射性肺炎,晚期反应为食管和肺损伤。两组的急性和晚期反应均较轻。结论：同期放化疗与后程加速超分割相比,显著提高了食管癌局控率,有提高生存率的趋势,毒性可以耐受。     

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 advanced esophageal carcinoma successfully treated with chemoradiation therapy with low-dose cisplatin and 5-fluorouracil

We have experienced a case of advanced esophageal carcinoma successfully treated with chemoradiation therapy together with low-dose cisplatin and 5-fluorouracil, having only minor toxicity. A 55-year-old man was admitted to our hospital because of dysphagia. Cervical esophageal carcinoma was found to have invaded the larynx through endoscopy, and invasion to thyroid gland and trachea was suspected from a cervical CT. We diagnosed the condition as advanced esophageal carcinoma (A2N(-)M0Pl0 Stage III). We then treated the patient by chemoradiation therapy. After the treatment, the carcinoma could not be detected by CT and endoscopy, and endoscopic biopsy revealed there were no active carcinoma cells. The side effects of the therapy were very mild, therefore the patient could be discharged after a short time. No evidence of a tumor relapse was found 5 months after the therapy. We treated 4 patients with esophageal carcinoma using the same regimen, and the results of the therapy were 2 CR, 1 PR, and 1 PD, with an overall response rate of 75%.     

多西他赛联合顺铂和5-氟尿嘧啶治疗晚期复治食管癌的临床疗效

目的探讨多西他赛联合顺铂和5-氟尿嘧啶治疗晚期复治食管癌的临床疗效。方法选取2012年5月至2016年5月间云南省肿瘤医院收治的80例晚期复治食管癌患者,采用等距随机抽样法分为观察组与对照组,每组40例。观察者患者采用多西他赛联合顺铂和5-氟尿嘧啶治疗,对照组患者采用多西他赛联合顺铂治疗,2个疗程后比较临床疗效。结果观察组患者治疗总有效率为62.5%,生活质量总分(88.14士1.21)分,对照组患者总有效率为47.5%,生活质量总分(75.33±1.25)分,两组比较差异均有统计学意义(均P<0.05);对照组患者不良反应发生率为15.0%,观察组患者为17.5%,两组比较差异无统计学意义(P>0.05)。结论多西他赛联合顺铂与5-氟尿嘧啶化疗方案治疗晚期复治食管癌疗效显著,可作为首选治疗方案推广使用。     

多西他赛联合顺铂治疗晚期食管癌临床观察

为了观察多西他赛联合顺铂(DDP)化疗方案治疗晚期食管癌的近期疗效和不良反应,制定化疗方案如下:多西他赛60mg/m2,静脉滴入1h,d1;DDP30mg/m2,静脉滴入,d2～d4。21d为1个周期,完成3个周期后判定疗效。全组病例110例:初治78例有效率46%(36/78),复治32例,有效率25%(8/32),总有效率40%(44/110)。主要毒副反应为恶心、呕吐和骨髓抑制。初步研究结果提示,多西他赛联合DDP是治疗晚期食管癌有效且毒性较少的联合化疗方案。     

替吉奥联合顺铂与5-氟尿嘧啶联合顺铂治疗晚期胃癌对照研究的Meta分析

目的:比较替吉奥联合顺铂方案(SP方案)和5-氟尿嘧啶联合顺铂方案(FP方案)一线治疗晚期胃癌的疗效及安全性。方法:计算机检索Pubmed、EMBASE、Cochrane Library、ASCO会议摘要、中国期刊全文数据库、中国生物医学文献数据库、中文科技期刊全文数据库等,同时追查纳入文献的参考文献,纳入SP方案对比FP方案治疗晚期胃癌的随机对照试验(RCT)。根据Cochrane Handbook 5.0的质量评价标准,用RevMan 5.0软件进行统计学分析。结果:纳入4项RCT,1 263例患者,Meta分析结果显示,采用SP方案与FP方案治疗后疗效相当(OR=1.58,95%CI:0.76～3.29,P=0.22),但可以降低3/4级血小板减少(OR=0.58,95%CI:0.40～0.85,P=0.004)及恶心呕吐(OR=0.70,95%CI:0.52～0.95,P=0.02)发生率;亚组分析(中国人群),纳入3项RCT,234例患者,Meta分析结果显示,与FP方案相比,SP方案可提高患者有效率(OR=2.39,95%CI:1.30～4.38,P=0.005),但不能降低不良反应发生率,差异均无统计学意义。结论:SP方案与FP方案在有效率方面疗效相当,但可以增加安全性,不良反应发生率与FP方案类似,但由于研究例数较少,该结论尚待进一步扩大样本量进行评估。     

Comparison of concurrent chemoradiotherapy with cisplatin plus 5-fluorouracil versus cisplatin plus paclitaxel in patients with locally advanced cervical carcinoma

Objective

The aim of this study was to compare survival outcomes and toxicities between concurrent radiotherapy with cisplatin plus 5-fluorouracil and that with cisplatin plus paclitaxel in patients with locally advanced cervical carcinoma.

Methods

We retrospectively reviewed data from 93 locally advanced cervical carcinoma patients (stage IB to IVA) who had been treated by concurrent radiotherapy with cisplatin plus 5-fluorouracil (CF, n=45) vs. cisplatin plus paclitaxel (CP, n=48) as primary therapy. Toxicities and survival outcomes were compared.

Results

In the CP group, there were higher frequencies of severe (grade 3 or 4) leukopenia (79.2%, as compared to 11.1% in the CF group), severe neutropenia (77.1%, as compared to 8.9% in the CF group) and severe peripheral neuropathy (12.5%, as compared to 2.2% in the CF group). In the CF group, there were higher frequencies of severe nausea (33.3%, as compared to 14.6% in the CP group) and severe hyponatremia (11.1%, as compared to 0% in the CP group). Five-year DFS of the CF and CP groups was 67.4% and 79.1%, respectively (p=NS). Five year OS of the CF and CP groups was 79.6% and 80.9%, respectively (p=NS).

Conclusion

Concurrent radiotherapy with cisplatin plus paclitaxel showed increased leukopenia, neutropenia and peripheral neuropathy, but less gastrointestinal toxicity (nausea) than that with cisplatin plus 5-fluorouracil. Survival outcome between these two groups was not statistically different in this study. Large prospective randomized controlled studies will be needed to confirm this result.     

紫杉醇联合DDP与奈达铂联合5-FU治疗晚期食管癌的临床观察

目的：比较紫杉醇联合DDP与奈达铂联合5-Fu治疗晚期食管癌的临床疗效及不良反应。方法：48例晚期食管癌随机分组,23例进入TP组（紫杉醇联合DDP）,25例进入NF组（奈达铂联合5-FU）。TP组：PTX135—175mg／m^2,静脉滴注3小时,d1,DDP20mg／m^2,静脉滴注,d1-5;NF组化疗方案：NDP80—100mg／m^2,静脉滴注2小时,d1,5-FU 500mg／m^2,d1-5;每3周为1个周期,至少完成2个周期。结果：TP组和NF组的有效率分别为52．5％和48．0％,两组无统计学差异（P〉0．05）。TP组不良反应较NF组明显严重,TP组主要为脱发、中性粒细胞减少、消化道反应、周围神经毒性,NF组主要为消化道反应、中性粒细胞减少。结论：TP方案与NF方案治疗晚期食管癌疗效相似,不良反应可以耐受,均可以用于晚期食管癌的治疗。     

Neoadjuvant chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil for esophageal cancer

Purpose

We aimed to evaluate the safety, tolerability, and efficacy of combination preoperative chemoradiotherapy as first-line treatment in patients with advanced esophageal cancer.

Methods

We performed a phase I dose-escalation trial of docetaxel at 25–40?mg/m² in four planned dose levels in 3–6 patient cohorts on days 1, 15, 29, and 43 administered in combination with cisplatin (70?mg/m² on days 1 and 29) and 5-fluorouracil (70?mg/m²/day on days 1–4 and 29–32) and concurrent radiation therapy (40?Gy). The tumors were resected during weeks 10–13.

Results

This study included 7 patients with esophageal cancer. The dose-limiting toxicity was observed at a biweekly docetaxel dose of 30?mg/m² when patients developed grade 3 febrile neutropenia, grade 4 thrombocytopenia, and grade 4 pain/esophagus, resulting in a maximum tolerated dose of 25?mg/m². Grade 3/4 hematological toxicity was observed in 71% of the patients and grade 3/4 non-hematological toxicity in 57%. The overall tumor response rate was 86% (complete, 57% and partial, 29%). All patients underwent surgery, and there were no deaths as a result of postoperative complications.

Conclusions

This preoperative chemoradiotherapy regimen using triplets is feasible but results in moderate toxicity. It is noteworthy that this regimen was associated with a high rate of pathological complete remission.     

紫杉醇联合DDP与奈达铂联合5-FU治疗晚期食管癌的临床观察

目的:比较紫杉醇联合DDP与奈达铂联合5-FU治疗晚期食管癌的临床疗效及不良反应.方法:48例晚期食管癌随机分组,23例进入TP组(紫杉醇联合DDP),25例进入NF组(奈达铂联合5-FU).TP组:PTX 135-175mg/m2,静脉滴注3小时,d1,DDP 20mg/m2,静脉滴注,d1-5;NF组化疗方案:NDP 80-100mg/m2,静脉滴注2小时,d1,5-FU 500mg/m2,d1-5;每3周为1个周期,至少完成2个周期.结果:TP组和NF组的有效率分别为52.5%和48.0%,两组无统计学差异(P＞0.05).TP组不良反应较NF组明显严重,TP组主要为脱发、中性粒细胞减少、消化道反应、周围神经毒性,NF组主要为消化道反应、中性粒细胞减少.结论:TP方案与NF方案治疗晚期食管癌疗效相似,不良反应可以耐受,均可以用于晚期食管癌的治疗.     

小剂量顺铂和氟尿嘧啶方案同步放射治疗中晚期食管癌

目的观察小剂量顺铂、氟尿嘧啶方案同步放射治疗中晚期食管癌的疗效及副作用。方法门诊收治中晚期食管癌190例,随机分为单放组(92例)和放化组(98例)。放疗采用常规分割,1.8～2.0Gy/次,5次/周,总剂量60～70Gy,6～7周完成。放疗同步使用顺铂4～6mg/m2+生理盐水200ml先行静脉滴入,氟尿嘧啶160mg/m2+5%葡萄糖注射液滴注6～8h,5次/周,连用4周。28d为1个周期,重复2～3个周期。结果单放组与放化组有效率分别为72.8%、82.7%,完全缓解率分别为34.8%、55.1%,部分缓解率分别为38.0%、27.6%;1、3、5年生存率分别为65.2%与82.7%、22.8%与37.8%、9.8%与17.3%;中位生存期分别为9.7、14.8个月。两组比较差异有统计学意义(P<0.05)。放化组发生急性消化道反应、白细胞下降等高于单放组,多数为1～2级。结论小剂量顺铂、氟尿嘧啶滴注方案联合放疗方案安全、费用低、疗效好,副作用轻微。     

Mature survival results with preoperative cisplatin,protracted infusion 5-fluorouracil,and 44-Gy radiotherapy for esophageal cancer

PURPOSE: To assess the long-term survival results after cisplatin, protracted infusion 5-fluorouracil, and concurrent radiotherapy (RT) followed by surgical resection of esophageal cancer. METHODS AND MATERIALS: Ninety-two patients with esophageal cancer (65 with adenocarcinoma and 27 with squamous cell carcinoma) were treated in two sequential protocols of preoperative chemoradiotherapy. The patients had tumor confined to the esophagus and regional nodes, including celiac nodes for middle and distal lesions. In trial A (1989-1994), 50 patients were treated with 44 Gy RT (2 Gy/d) along with concurrent 5-fluorouracil 300 mg/m(2)/d given by protracted venous infusion on Days 1-30 and cisplatin 26 mg/m(2) on Days 1-5 and 26-30. In trial B (1995-1997, 42 patients), the chemotherapy dosages during RT were reduced to 5-fluorouracil 225 mg/m(2)/d protracted venous infusion and cisplatin 20 mg/m(2)/d on Days 1-5 and 16-30; three cycles of paclitaxel 135 mg/m(2)and cisplatin 75 mg/m(2) were given postoperatively. Surgery generally occurred 4-6 weeks after completion of the planned preoperative therapy. Transhiatal resection was performed whenever possible. RESULTS:Of the 92 patients, 86 (93%) underwent surgery (1 refused, 2 died preoperatively, and 3 developed evidence of metastatic disease). Of the 92 patients, 80 (87%) had complete resections with negative margins (3 had positive margins and 3 had distant metastases discovered at surgery). The pathologic complete response rate was 33% (30 of 92). The median follow-up was 63.5 months. The median survival and disease-specific survival for all enrolled patients was 35 and 59 months, respectively. The 5-year survival and disease-specific survival rate was 40% and 49%, respectively. Patients with a pathologic complete response had a 67% survival rate at 5 years (median not reached), and the remainder of patients had a 5-year survival rate of 27% (median 21 months; p <0.001). For 21 patients alive after 5 years (60-121 months), 2 died of their disease and all others were disease free. Eight patients with pathologic Stage I tumor at the time of surgery had survival similar to those with a complete response to preoperative therapy. The median survival for patients with pathologic Stage IIA, IIB, III, and IV disease at the time of surgery was 22, 13.5, 18, and 4.9 months, respectively. The pattern of initial failure was local/regional alone in 6% (5 of 90), local/regional plus distant in 3% (3 of 90), and distant alone in 47% (42 of 90). No differences were noted in survival or response rate between those with adenocarcinoma or squamous cell carcinoma. CONCLUSION: The promising 5-year survival results and low rate of late cancer-related deaths suggest that these regimens of intensive neoadjuvant therapy may improve the overall cure rate. The pathologic stage after neoadjuvant therapy is an important predictor of survival and may be useful in selecting patients for novel adjuvant therapies. Isolated local failure is uncommon, indicating that efforts to improve the therapeutic outcome should focus on optimizing systemic therapy rather than intensifying the RT. Additional randomized data are needed to assess the benefits of this therapeutic approach fully.     

Results of a randomised phase II study of cisplatin plus 5-fluorouracil versus cisplatin plus 5-fluorouracil with alpha-interferon in metastatic pancreatic cancer: an EORTC gastrointestinal tract cancer group trial

A randomised phase II study of 5-fluorouracil (5-FU) plus cisplatin (CDDP) with or without alpha-interferon 2b was performed in patients with pancreatic cancer with measurable metastatic disease outside the pancreas. The treatment in arm A consisted of cisplatin (100 mg/m(2)) on day 1, followed by a continuous infusion of 5-FU 1000 mg/m(2) for 4 days and in arm B the same treatment was given plus alpha-interferon 2b in a dose of 3 million Units/day subcutaneously (s.c.) from day 1 for 5 days. 36 patients were entered in the trial, 18 in each arm. In arm B only 15 patients were eligible. No responses were observed in the 5-FU/CDDP arm and only 2 partial responses were achieved in the interferon-arm, lasting 27 and 32 weeks, respectively. Both treatment arms showed considerable toxicity. It has to be concluded that both treatment regimens have little activity and cannot be recommended.     

多西他赛联合顺铂和氟尿嘧啶治疗晚期胃癌疗效观察

目的观察多西他赛联合顺铂、氟尿嘧啶(DCF方案)治疗晚期胃癌的疗效和不良反应。方法采用DCF方案治疗33例晚期胃癌患者。多西他赛75 mg/m2,d1;顺铂75 mg/m2,d1;氟尿嘧啶750 mg/m2,持续静脉滴注,d1~5,3周1个周期,至少2个周期。结果33例晚期胃癌中,完全缓解(CR)0例,部分缓解(PR)18例(54.5%),稳定(SD)8例(24.2%),进展(PD)7例(21.2%)。中位肿瘤进展时间为6.1个月(3.5~11.5个月),中位总生存期为11.2个月(6.0~14.5个月)。最常见的不良反应为骨髓抑制、消化道反应及可逆性体液潴留,不良反应多为Ⅰ~Ⅱ度,无Ⅳ度不良反应发生。骨髓抑制以白细胞减少为特点,血小板减少及贫血较轻。消化道反应主要表现为恶心呕吐、腹泻、便秘,无Ⅳ度腹泻发生。无治疗相关性死亡。结论DCF方案是治疗晚期胃癌安全有效的化疗方案。     

Outpatient therapy with irinotecan and low-dose cisplatin for metastatic colorectal cancer resistant to 5-fluorouracil

Chemotherapy with irinotecan hydrochloride and low-dose cisplatin was tested for the treatment of metastatic colorectal cancer showing resistance to 5-fluorouracil. Eleven consecutive patients with advanced metastatic colorectal cancer (performance status: 0 to 2), who had shown tumor progression on chemotherapy with 5-fluorouracil/leucovorin, were treated with irinotecan (60 mg/m2) plus cisplatin (6 mg/m2) by 90-min intravenous infusion. Treatment was repeated weekly for 3 weeks during admission and then fortnightly on an outpatient basis. Objective responses were observed in four patients (36%; 95% confidence interval: 11%-69%). The median duration of response was 5.5 months and six patients are still alive. The time to disease progression was longer in the no change group (7.0+/-3.6 months: mean +/- SD) than in the responder group (5.5+/-1.9 months), and there was no difference of median survival between the two groups (10.0 versus 10.3 months). The overall median survival was 8.2 months (range: 4 to 12+ months). This treatment was well tolerated. Six patients experienced grade 1 or 2 leucopenia, while grade I diarrhea and nausea occurred in three and five patients, respectively. Based on the good response, excellent quality of life, and convenience, the present regimen seems to be reasonable second-line outpatient chemotherapy for patients with metastatic colorectal cancer showing resistance to 5-fluorouracil.     

Feasibility of chemoradiation therapy with protracted infusion of5-fluorouracil for esophageal cancer patients not suitable for cisplatin

Background Chemoradiation therapy is the standard treatment for esophageal cancer in patients not fit for surgery. The regimen most commonly used includes cisplatin and 5-fluorouracil. Little data exists regarding alternative chemotherapy regimens in patients not suitable for cisplatin. We report on a regimen using protracted infusion 5-fluorouracil alone for both curative and palliative indications.Methods Twenty-two patients with localized esophageal cancer suitable for curative chemoradiation therapy and24 patients suitable for palliative therapy were enrolled. Chemotherapy consisted of 5-fluorouracil 225 mg/m² daily throughout the radiation therapy. The radiation dose was 56 to 60 Gy in 28 to 30 fractions (curative patients) and 30 to 35 Gy in 15 fractions (palliative patients).Results The median age of the patients was 75 years. The regimen was tolerable. Significant grade 3 toxicities experienced were esophagitis (11%) and venous catheter toxicity (9%). The median survival was 17 months for curative patients and 9 months for palliative patients. The complete response rate was 86% endoscopically and 45% radiologically for curative patients. Relief of dysphagia was experienced in 67% of palliative patients. Quality of life was satisfactory in both groups.Conclusions This study showed that continuous-infusion5-fluorouracil given concurrently with radiation therapy isa useful alternative to platinum-based chemoradiation therapy in patients with esophageal carcinoma.