Induction chemotherapy with docetaxel, cisplatin, fluorouracil and l-leucovorin for locally advanced head and neck cancers: a modified regimen for Japanese patients

Combination chemotherapy with docetaxel (T), cisplatin (P), fluorouracil (5-FU) and leucovorin has been reported to have major activity against squamous cell carcinoma of the head and neck (SCCHN) administered as a 4-day (TPFL4) or 5-day (TPFL5) regimen. The purpose of this study was to evaluate the efficacy and toxicity of a modified TPFL regimen (m-TPFL) for locally advanced SCCHN, consisting of a modified dosage with docetaxel, cisplatin, 5-FU and l-leucovorin (l-LV) designed for Japanese patients. Organ preservation of the primary tumor site was also assessed. Thirty-four Japanese patients with locally advanced SCCHN were eligible. Docetaxel was administered as a 1-h i.v. infusion at 48 mg/m2 on day 1; cisplatin, 24 mg/m2/day; 5-FU, 560 mg/m2/day and l-LV, 125 mg/body/day were delivered on days 1-4 by continuous i.v. infusion. This regimen was administered every 28 days. Patients who achieved a complete response (CR) after induction chemotherapy underwent radiation therapy alone. Ninety-one cycles were administered. The main hematological toxicity was neutropenia, classified as grade III or IV in 18.7% of cycles. The most common non-hematologic toxicities included anorexia, stomatitis and alopecia. The clinical overall response rate to m-TPFL was 88.2%, with 58.8% CRs and 29.4% partial responses. After definitive locoregional therapy, 25 of 34 patients were disease-free with preserved primary tumor site anatomy. Overall and progression-free survival rates at the 2-year follow-up are 92.8 and 75.3%, respectively. Our m-TPFL regimen designed for Japanese patients yielded excellent response rates with an acceptable toxicity profile in good-performance-status patients.     

The chemotherapy of head and neck cancer

Studies of combination therapy [with agents such as cisplatin, 5-fluorouracil (5-FU) and methotrexate] have shown some improvements in response rate; however, no obvious survival advantage over monotherapy in the treatment of patients with metastatic or advanced locoregional cancer of the head and neck have been observed. In the neoadjuvant setting, chemotherapy is helpful in preserving the larynx and hypopharynx but has no proven impact (positive or negative) on survival. New treatment options are needed to improve survival in head and neck cancer. Among the new options for chemotherapy in metastatic/recurrent disease is docetaxel. With monotherapy, response rates of 23-42% are seen, and, when used in combination with cisplatin and 5-FU, response rates of 52-100% have been reported in phase I/II trials. A phase III trial of the addition of docetaxel to standard neoadjuvant therapy with cisplatin and 5-FU is now underway.     

Available options in chemotherapy for advanced gastric cancer: the current developments in Japan

Although techniques for early diagnosis and treatment of gastric cancer have been established, standard treatment for advanced gastric cancer has not. 5-Flourouracil (5-FU) plus cisplatin containing regimens, including 5-FU plus cisplatin, epirubicin plus cisplatin and 5-FU, and docetaxel plus cisplatin and 5-FU, are considered to be the most effective regimens for advanced gastric cancer in US, Europe and Korea. In Japan, oral fluoropyrimidine S-1 is currently considered to be the first-line treatment for advanced gastric cancer. S-1-based combination therapies with other promising drugs, including cis-platin, irinotecan and taxanes, are expected to yield good results. Above all, S-1 plus cisplatin therapy showed high efficacy and expected to be a standard therapy for advanced gastric cancer. Further evaluation by well-controlled clinical trials is still required.     

Adjusting for patient selection suggests the addition of docetaxel to 5-fluorouracil-cisplatin induction therapy may offer survival benefit in squamous cell cancer of the head and neck

When induction chemotherapy is used in locally advanced squamous cell cancer of the head and neck (SCCHN), patients often receive cisplatin-5-fluorouracil (PF) followed by radical loco-regional therapy. Phase II studies of docetaxel-cisplatin-5-fluorouracil (TPF) induction therapy, with or without leucovorin (L), have achieved high survival rates versus those reported in phase III PF trials. However, the distribution of prognostic factors may vary between phase II and phase III study populations, making the extrapolation of phase II TPF/L results to phase III PF populations difficult. This study used a patient selection standardization method and Cox model to adjust for potential selection bias. Thus, the survival benefit from adding docetaxel into PF induction regimens in SCCHN could be more accurately assessed. The TPF/L dataset comprised 195 patients from six phase II trials. The PF dataset of 585 patients was derived from five large randomized trials included in the Meta-Analysis of Chemotherapy in Head and Neck Cancer (MACH-NC) database. TPF/L and PF datasets differed significantly concerning the distribution of several prognostic factors. Adjusting for these differences, the relative risk of death in the PF versus TPF/L datasets was 1.85 (95% confidence interval 1.37-2.49), corresponding to a 20% 2-year survival benefit (p < 0.0001). Sensitivity analyses confirmed that this improved 2-year survival rate of TPF/L over PF was robust, irrespective of the distribution of studied prognostic factors between treatment datasets. We conclude that this improved survival might be due either to docetaxel's pharmacologic effect or to uncontrolled prognostic factors.     

Clinical advances with topoisomerase I inhibitors in gastrointestinal malignancies

Phase III studies have shown irinotecan prolongs survival significantly when compared with either best supportive care or best infusional 5-fluorouracil (5-FU)-based chemotherapy in patients with 5-FU-resistant colorectal cancer. Phase I/II studies are investigating the combination of irinotecan with 5-FU, with thymidylate synthase inhibitors, notably raltitrexed, and with the oral fluoropyrimidines. Preliminary results suggest irinotecan and raltitrexed can safely be combined in the clinic and that this combination is active. The combination of irinotecan with the oral fluoropyrimidines also has produced promising results. A phase I study of irinotecan plus 5-FU/folinic acid showed high activity in first-line metastatic disease and further trials using the doses of 80 mg/m2 irinotecan plus 2 g 5-FU weekly are recommended. The combination of irinotecan with the De Gramont 5-FU regimen is feasible and active in patients with 5-FU-resistant metastatic disease. Alternating exposure to irinotecan and 5-FU may be as active as either treatment alone, and has been associated with overall response rates (ORRs) greater than 30% and encouraging median survival. The combination of irinotecan with oxaliplatin is also feasible and levels of response rates are in the region of 50% (especially with a 2-weekly administration schedule). In patients with advanced gastric cancer (including those with pretreated disease) ORRs of around 50% have been reported following administration of either cisplatin plus irinotecan or cisplatin plus docetaxel.     

Pemetrexed: new drug. Pleural mesothelioma: a first encouraging trial

(1) Chemotherapy does not appear to prolong the survival of patients with inoperable pleural mesothelioma, and the tumour response rate barely exceeds 20%. A combination of cisplatin + doxorubicin seems to provide the best response rates. (2) In a trial of second-line docetaxel therapy in patients with non small cell lung cancer, survival was extended by about 3 months compared with palliative care (7.5 versus 4.6 months). (3) Pemetrexed, an antifolate closely related to methotrexate and raltitrexed, has been authorized for use for both conditions. (4) In a randomised single-blind trial involving 456 patients with previously untreated pleural mesothelioma, survival was prolonged by about 3 months by a cisplatin + pemetrexed combination in comparison with cisplatin + placebo (12.1 versus 9.3 months). The respective tumour response rates were 41.3% and 16.7%. This is the only available comparative trial of pemetrexed in patients with mesothelioma. A more appropriate comparator would have been a cisplatin-based regimen such as cisplatin + doxorubicin. (5) A "non inferiority" trial of second-line treatment in 571 patients with locally advanced or metastatic non small cell lung cancer showed no significant difference in median survival time with pemetrexed versus docetaxel (about 8 months with both treatments). However, this trial does not rule out the possibility that pemetrexed is less effective than docetaxel. (6) Supplementation with folic acid and vitamin B12 reduces haematological and gastrointestinal complications associated with the antifolate activity of pemetrexed. (7) Despite this supplementation, more than 15% of patients in the mesothelioma trial developed severe neutropenia, leukopenia or fatigue during cisplatin + pemetrexed therapy. Pemetrexed aggravates the nausea and vomiting provoked by cisplatin, a drug that is highly emetic. (8) The adverse effects of pemetrexed were similar to those of docetaxel in the trial comparing the two drugs. However, neutropenia (5% versus 40%) and febrile neutropenia (2% versus 13%) occurred less frequently with pemetrexed. (9) Patients receiving pemetrexed must be monitored closely for some rare but potentially severe adverse effects; they include angina, myocardial infarction and stroke, liver damage, and bullous skin rash. (10) According to the summary of product characteristics (SPC), pemetrexed therapy must be administered in combination with folic acid and vitamin B12 supplementation in order to reduce haematological toxicity, and also with corticosteroid therapy to reduce the risk of serious skin reactions. (11) In practice, given the absence of a better alternative, and pending the results of a second trial, the cisplatin + pemetrexed combination can be used as a first-line regimen for patients with pleural mesothelioma. However, pemetrexed cannot replace docetaxel in second-line treatment of non small cell lung cancer.     

Docetaxel in advanced gastric cancer

Standard chemotherapy for advanced gastric cancer remains undefined. Two of the most popular regimens-ECF [epirubicin-cisplatin-5-fluorouracil (5-FU)] and PELF (cisplatin-epirubicin-5-FU-leucovorin)-have been shown to be active, but each has limitations. Phase II trials show that single-agent docetaxel is an active agent in advanced gastric cancer, producing overall response rates (ORRs) of 17.5-24%. Docetaxel has also been shown to lack cross-resistance with other drugs in gastric cancer, and is likely to be at least additive to cisplatin and 5-FU. Phase II results of docetaxel combinations in advanced gastric cancer are encouraging. Docetaxel-cisplatin has yielded response rates similar to those achieved by ECF and PELF. Adding 5-FU to docetaxel-cisplatin has achieved an ORR of 52 versus 45% for docetaxel-cisplatin in a randomized phase II trial. Docetaxel-based regimens demonstrate acceptable tolerability despite predictable hematotoxicity. Neutropenia, the major toxicity, is manageable by dose modification or by using prophylactic granulocyte colony stimulating factor. Several phase III trials are now ongoing, including a large-scale trial of docetaxel-cisplatin-5-FU versus cisplatin-5-FU. Results will show whether docetaxel improves overall response and survival, as suggested in the phase II setting.     

多西他赛联合顺铂同步放化疗治疗局部晚期食管癌的疗效分析

目的研究多西他赛联合顺铂化疗同步三维适形放射治疗(3D-CRT)治疗局部晚期食管癌的近期疗效及毒副反应。方法将68名经病理确诊的食管癌局部晚期患者随机分为DP治疗组33例和PF治疗组35例。DP治疗组采用多西他赛联合顺铂,PF治疗组采用5-氟尿嘧啶联合顺铂,两组均采用3D-CRT计划,照射剂量为56～60Gy,2Gy/次,5次/周。结果 DP治疗组的总反应率为90.9%,PF治疗组的总反应率为82.9%;DP治疗组1、2年的总生存率分别为81.8%和48.5%;PF治疗组1、2年的总生存率分别为74.3%和37.1%;差异有统计学意义(P<0.05)。结论多西他赛联合顺铂化疗同步三维适形放射治疗治疗局部晚期食管癌近期疗效较好,但是还需要进行长期的随访观察。     

The current status of docetaxel for advanced non-small cell lung cancer

Docetaxel is an active single agent in both first- and second-line therapy of patients with advanced non-small cell lung cancer (NSCLC). Randomized trials versus best supportive care have documented an improvement in overall survival for docetaxel therapy in both settings. Docetaxel also produced a significant 1-year survival rate improvement when compared with vinorelbine or ifosfamide as second-line therapy. Docetaxel has been extensively investigated in phase I/II studies in combination with cisplatin, carboplatin, irinotecan and gemcitabine. Substantial activity has been demonstrated. In a randomized phase II trial comparing docetaxel plus cisplatin with docetaxel plus gemcitabine, the efficacy of the two regimens was almost identical (response rates 32 and 34%; 1-year survival rates 42 and 38%). However, the combination of docetaxel with gemcitabine was associated with significantly less grade III/IV neutropenia, diarrhea and nausea/vomiting. Three drug regimens combining docetaxel with, for example, gemcitabine and carboplatin or with ifosfamide and cisplatin, are producing very high response rates in phase II trials. Whether three-drug combinations including docetaxel will result in an improved outcome for patients with advanced NSCLC remains to be determined.     

多西他赛联合顺铂方案新辅助治疗局部晚期食管鳞癌的临床研究

目的分析比较多西他赛联合顺铂方案(TP)与氟尿嘧啶联合顺铂方案(PF)新辅助治疗局部晚期食管鳞癌的有效性及安全性。方法收集自2010年6月至2013年3月在我院肿瘤内科和胸心外科住院新辅助化疗的局部晚期食管鳞癌患者94例,其中TP方案组42例(DTX 75 mg/m2,静滴d1,DDP 20 mg/m2,静滴d1^d3)和PF组52例(5-FU 1000 mg/m2,静滴d1d3)和PF组52例(5-FU 1000 mg/m2,静滴d1^d5;DDP 20 mg/m2,静滴d1d5;DDP 20 mg/m2,静滴d1^d3,q4周)组。化疗3周期后评价疗效及毒副反应。结果全部入组病例均可评价近期疗效和毒副反应。TP组患者的近期有效率明显高于PF组(P<0.05);然而疾病控制率相似,无统计学意义(P=0.344);两组化疗方案的3d3,q4周)组。化疗3周期后评价疗效及毒副反应。结果全部入组病例均可评价近期疗效和毒副反应。TP组患者的近期有效率明显高于PF组(P<0.05);然而疾病控制率相似,无统计学意义(P=0.344);两组化疗方案的3⁴级毒副反应方面比较,毒副作用均可耐受,恶心呕吐、过敏、乏力、腹泻的34级毒副反应方面比较,毒副作用均可耐受,恶心呕吐、过敏、乏力、腹泻的3⁴级不良反应发生率两组比较差异无统计学意义(P>0.05)。骨髓抑制、神经毒性及肌痛差异具有显著性(P<0.05)。结论在局部晚期食管鳞癌新辅助化疗中,TF方案与PF方案比较,具有更好的近期有效率,但有更高的毒副反应,经过及时处理后PF方案可具有较好的耐受性。     

多西紫杉醇加顺铂及氟尿嘧啶化疗辅助治疗进展期胃癌

目的研究多西紫杉醇加顺铂及氟尿嘧啶(5-FU)/亚叶酸钙方案联合新辅助化疗治疗局部进展期胃癌,并评价此方案的疗效和毒副作用。方法2003-10～2004-10收治的18例局部进展期胃癌患者加入研究。入组患者术前接受的新辅助化疗方案为:多西紫杉醇75mg/m2,第1天静脉滴注;顺铂30mg/m2,第1～3天静脉滴注;5-FU500mg/m2,第1～5天静脉滴注;亚叶酸钙100mg于5-FU前30min静脉冲入;每3周为1周期,共3个周期。观察新辅助化疗后肿瘤原发病灶的缓解情况、手术后病理缓解情况以及新辅助化疗的毒副反应。结果新辅助化疗后所有患者进行了根治性手术治疗,有效10例,其中完全缓解3例,部分缓解7例;疾病稳定5例,疾病进展3例。术后病理检查2例病理水平达到完全缓解。不良反应主要为白细胞减少、恶心、脱发、呕吐及黏膜炎,其中有4例患者发生了Ⅲ～Ⅳ级的白细胞减少,但未有因此而发生严重感染和病死者。结论多西紫杉醇加顺铂及5-FU/亚叶酸钙的化疗方案在进展期胃癌的治疗中近期疗效显著,患者耐受性良好。     

DOF与DCF方案治疗进展期胃癌的临床对照观察

目的:本研究旨在评价多西他赛联合奥沙利铂、氟脲嘧啶(DOF方案)与多西他赛联合顺铂、氟脲嘧啶(DCF方案)组成的5天联合方案一线治疗进展期胃癌的有效性和安全性。方法:75例患者分为A、B两组。A组38例,接受DOF方案:多西他赛75mg/m2第2天,奥沙利铂130mg/m2第1天,氟脲嘧啶500mg/m2第1～5天;B组37例,接受DCF方案:多西他赛75mg/m2第2天,顺铂25mg/m2第1～3天,氟脲嘧啶500mg/m2第1～5天。均每3周重复,至少应用2周期。结果:A组患者临床控制率、完全缓解率、部分缓解、中位治疗至进展时间、中位生存期以及1年生存率和2年的生存率分别为65.78%、5.26%、42.10%、5.9月、11.2月、52.63%、18.42%。B组分别为54.06%、2.70%、35.14%、5.8月、10.8月、48.64%、13.51%。治疗前两组生活质量(QOL)分值相当,但是治疗后1月、2月的QOL分值有差异(P<0.05)。两组生存期比较无显著差异(P>0.05)。两组主要毒副反应为骨髓抑制、恶心呕吐,但不严重。结论:多西他赛联合奥沙利铂、氟脲嘧啶和多西他赛联合顺铂、氟脲嘧啶一线治疗进展期胃癌疗效均确切、毒副反应均可以接受。与最好的支持治疗相比联合化疗可延长患者生存期,提高生活质量。特别是前者对生活质量的影响比后者轻。     

Docetaxel: new indication. First-line treatment of non small-cell lung cancer: no advance

(1) The reference first-line drug therapy for patients with non-operable non small-cell lung cancer is a combination of two cytotoxic agents, one of which is a platinum compound. The survival benefit is no more than a few months. (2) The docetaxel + cisplatin combination has now been authorised in France for first-line treatment of locally advanced and metastatic non small-cell lung cancer. Evaluation data includes the results of three comparative trials. (3) In one trial the docetaxel + cisplatin combination was no more effective than the docetaxel + carboplatin combination or the vinorelbine + cisplatin combination on either the survival time (9.4 to 11.3 months) or on other endpoints. (4) Similar results were obtained in a trial versus paclitaxel + cisplatin and gemcitabine + cisplatin (median survival time 8 months in each group). (5) In a trial versus vindesine + cisplatin, the median survival time was longer with docetaxel + cisplatin (11.3 versus 9.6 months). (6) It is difficult to analyse adverse effects in these unblinded trials. Globally, the docetaxel + cisplatin combination did not appear to be safer than the comparator combinations, particularly with regard to serious events. (7) Docetaxel, like paclitaxel, is infused intravenously every three weeks. The comparator combinations tested in the three clinical trials are infused once a week. (8) In practice, for first-line treatment of inoperable non small-cell lung cancer, the docetaxel + cisplatin combination is simply one of several options, and offers no advantages in terms of survival or adverse effects.     

Phase II study with 5-fluorouracil and ginkgo biloba extract (GBE 761 ONC) in patients with pancreatic cancer

The aim of the study was to evaluate the efficacy and tolerability of as well as the quality of life under treatment with 5-fluorouracil (CAS 51-21-8, 5-FU) combined with parenteral GBE 761 ONC (i.e. the ginkgo biloba special extract EGb 761) in patients with pancreatic cancer. Forty-eight patients with locally or metastatic advanced pancreatic cancer were treated within a phase II study. The treatment was repeated every three weeks until progression. Response to therapy was evaluated after 2 and 4 treatment courses. Thirty-two patients were evaluable for response. Progressive disease was observed in 22 (68.8%) patients, no change in 7 (21.9%) patients and partial response in 3 (9.4%) patients (overall response = 9.4%). GBE 761 ONC was well tolerated. Adverse events which occurred during the study consisted mainly of myelosuppression and gastrointestinal symptoms and were judged as 5-FU-related or consisted of liver toxicity, respectively, and were judged as tumour-related. These results suggest a good benefit-risk ratio of the combination of 5-FU and GBE 761 ONC in the treatment of pancreatic cancer. In comparison with the results of studies with either 5-FU or gemcitabine as single agents the combination of 5-FU/GBE 761 ONC shows comparable response rates. The toxicity of the 5-FU/GBE 761 ONC combination was low. This combination therapy therefore warrants further clinical investigation, such as a controlled clinical trial against 5-FU or gemcitabine monotherapy.     

多西紫杉醇联合草酸铂和5-氟尿嘧啶治疗晚期耐药性胃癌

目的观察多西紫杉醇(DOC)联合草酸铂(L-OHP)和5-氟尿嘧啶(5-FU)方案治疗进展期胃癌一线方案失败的疗效及毒副作用。方法采用DOC75mg/m2,第1天;L-OHP100～130mg/m2;醛氢叶酸0.2/m2第1、2天;5-FU500mg第1、2天;5-FU2.0/m2微量泵持续静脉滴注48h,21d为1个周期,连用3个周期进行评价。共治疗37例进展期胃癌患者。结果37例患者均可评价,获得CR0例,PR11例(29.73%),SD13例(35.14%);PD13例(35.14%):临床受益率(CBR)为78.38%%。与药物相关的不良反应依次为:Ⅱ～Ⅲ度白细胞减少26例(70.27%);Ⅱ～Ⅲ度血小板减少14例(37.84%);Ⅱ～Ⅲ度恶心、呕吐21例(56.76%);Ⅱ～Ⅲ度腹泻19例(51.35%);Ⅰ～Ⅱ度神经毒性反应22例(59.46%)。结论DOC、L-OHP和5-FU联合方案治疗进展期耐药性胃癌患者有效,毒副反应少,患者临床受益。     

Docetaxel (Taxotere) - an update

The development of docetaxel, a member of the taxoid family, has been recent and rapid. Phase I studies recommend that a dose of 100 mg/m(2) be administered every three weeks in a 1-h infusion. These studies have also demonstrated that the major dose-limiting toxicity is neutropenia. Major clinical research projects are now being carried out for breast cancer, non-small-cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN) and gastric cancer. In advanced and metastatic NSCLC, Phase II studies have shown a response rate of 30 - 40%, and responses have been obtained in cis-platinum failures. In advanced and metastatic breast cancer, first-line treatment has yielded a response rate of 54 - 68%, and the rate for second-line response is only slightly lower, indicating an absence of cross-resistance. Phase II combination studies with docetaxel are in progress, and preliminary results are promising. The first Phase III study demonstrated preliminary response rates significantly higher than seen with doxorubicin, although survival data have not yet been published. Fewer results are available from SCCHN studies, but response rates have been encouraging (around 40%). Although further long-term data are needed to determine the precise role of docetaxel in combination with other drugs, it is apparent that this promising drug shows one of the best response rates for monotherapy in NSCLC and breast cancer.     

DCF方案一线治疗进展期胃癌的临床疗效观察

目的 观察DCF方案(多西他赛+顺铂+氟尿嘧啶)一线治疗进展期胃癌的临床疗效和不良反应.方法 收集我院2007年7月至2011年2月经病理和影像学确诊的61例进展期胃癌患者的临床资料进行回顾性分析.DCF方案:多西他赛75 mg/m2静脉滴注,第1天;氟尿嘧啶750 mg/m2持续静脉滴注24h,用化疗泵持续静脉滴注120 h(第1～5天);顺铂75 mg/m2第1天静脉滴注,所有患者至少用药3个周期.对近期客观疗效及不良反应进行评价.结果 治疗有效率为34.4％(21/61),疾病控制率为82.0％(50/61),中位无疾病进展时间为6.2个月,中位总生存期为10.1个月.中性粒细胞减少发生率为86.9％(53/61),其中Ⅲ～Ⅳ级为72.1％ (44/61),恶心呕吐发生率为80.3％(49/61),Ⅲ～Ⅳ级占18.0％(11/61).结论 DCF方案一线治疗进展期胃癌疗效较好,但骨髓抑制毒副作用较明显,可以作为一般状态较好的进展期胃癌患者有效化疗方案的选择.     

多西紫杉醇联合顺铂治疗蒽环类耐药的晚期乳腺癌的临床疗效观察

目的观察多西紫杉醇联合顺铂治疗蒽环类耐药的晚期乳腺癌的疗效与不良反应。方法 2003年6月至2007年6月,我科以多西紫杉醇联合顺铂治疗蒽环类耐药的晚期乳腺癌36例。多西紫杉醇75mg/m2,静脉点滴,第1天;顺铂30mg/（m2.d）,静脉点滴,第1天至第3天;每21d为一周期,至少两个周期后评价疗效。本组中位化疗周期数为4（2-6）周期。结果 36例均可评价疗效。完全缓解（CR）2例（5.6%）,部分缓解（PR）18例（50%）,稳定（SD）9例（25%）,进展（PD）7例（19.4%）,总有效率（CR＋PR）55.6%,中位肿瘤进展时间6个月,一年生存率71%,中为生存时间16个月。主要的不良反应为胃肠道反应和骨髓抑制。结论多西紫杉醇联合顺铂治疗蒽环类耐药的晚期乳腺癌疗效较好,不良反应可以耐受,是蒽环类耐药的晚期乳腺癌的有效解救方案。     

Treatment of advanced digestive non-colon cancer with a weekly 24-h infusion of high-dose 5-fluorouracil modulated by folinic acid and cisplatin: an easy-to-use and well-tolerated combination

The combination of 5-fluorouracil (5-FU) modulated by folinic acid (FA) and cisplatin is commonly used in advanced digestive non-colon cancers (ADNCC). In order to simplify treatment administration by avoiding cisplatin-related hydration, we investigated a weekly regimen of 5-FU/FA/cisplatin. Patients with ADNCC were treated with 5-FU 2.0 g/m2, FA 500 mg/m2 and cisplatin 25 mg/m2 day 1, for 6 weeks with a 2-week rest, and were assessed for toxicity, tumor response and disease-free survival. Forty-three patients with measurable ADNCC were treated with this weekly regimen. Primary tumor sites were mainly esophagus (n = 17), stomach (n = 12) and pancreas (n = 9). Results were as follows. Toxicity was mostly hematological, with 16% grade 3/4 neutropenia (seven of 43) and 4% febrile neutropenia (two of 43). Objective response (OR) was observed in 19 of 43 (44%) patients including four complete responses (9%) and 15 partial responses (35%). Another 18 patients (42%) experienced stable disease. Time to progression was 6.5 months. The median response and stable disease durations were 4.3 (range 3-34) and 5 (range 2-16) months, respectively. We conclude that weekly administration of 5-FU/FA/cisplatin is an active and well-tolerated regimen. Toxicity is manageable and allows chemotherapy on an outpatient basis without hydration program as required when cisplatin is used at the dose of 50 mg/m2.