A phase I/II trial of docetaxel and oxaliplatin in patients with advanced gastric cancer

Purpose  We designed this phase I/II study of docetaxel–oxaliplatin combination chemotherapy to determine the dose-limiting toxicity (DLT), maximum tolerated dose and efficacy as a first-line treatment in patients with advanced gastric cancer. Methods  Patients with histologically proven, chemo-naive gastric adenocarcinoma were eligible. For the phase I part, three dose levels of oxaliplatin and docetaxel every 3 weeks were tested in a cohort of three patients for each level (respectively, 100 and 60 mg/m², 100 and 75 mg/m², 130 and 75 mg/m²). Patients were treated up to a maximum of nine cycles of oxaliplatin and docetaxel unless there was documented disease progression, an unacceptable adverse event, or withdrawal of consent. Results  No DLT was observed at any of the three levels tested in the phase I portion. Therefore, oxaliplatin 130 mg/m² and docetaxel 75 mg/m² were recommended for the phase II study. All 47 patients were evaluable for toxicity and treatment response. The overall response rate was 55.3% (95% CI, 40.6–70.1%) and median duration of response was 4.2 months (range 0.9–9.5 months). After a median follow-up duration of 13.3 months, median overall survival was 12.7 months (95% CI: 10.4–14.9). The median time to progression was 5.0 months (95% CI, 3.4–6.5 months). The main toxicities (grade 3 or 4) were febrile neutropenia (14.9%), neutropenia (23.4%), diarrhea (10.6%) and neurotoxicity (8.5%). Conclusion  The combination of docetaxel and oxaliplatin was feasible with favorable toxicity profile and showed a promising anti-tumor activity in unresectable, metastatic gastric cancer patients.     

A phase II study of docetaxel as salvage chemotherapy in advanced gastric cancer after failure of fluoropyrimidine and platinum combination chemotherapy

Purpose Fluoropyrimidine (F) and platinum (P) combination chemotherapy has been widely used as a first-line treatment of advanced gastric cancer (AGC). Docetaxel has shown promising activity against this disease. In this study, we explored the efficacy and safety of docetaxel monotherapy as salvage chemotherapy in AGC after F and P combination chemotherapy failed. Materials and methods From October 2004 to October 2005, 49 eligible patients were enrolled in this study. The median treatment-free interval was 28.0 days, and 81.6% of patients had suffered cancer progression within 4 months after the withdrawal of first-line chemotherapy. Docetaxel was given IV at a dose of 75 mg/m² every 3 weeks, together with dexamethasone prophylaxis. Results A total of 182 cycles of docetaxel were administered with a median of 3 (range 1–9) cycles. From an intention-to-treat analysis, eight patients achieved objective response with a response rate of 16.3% (95% CI, 6.0–26.6). The median response duration was 4.7 months. A total of 20 patients showed stable disease, but 17 patients suffered disease progression. At a median follow-up duration of 11.3 months for surviving patients (range 6.3–18.8 months), the median time to disease progression was 2.5 months (95% CI, 2.3–2.7) and the median overall survival time since the start of docetaxel monotherapy was 8.3 months (95% CI, 6.7–9.8). Grade 3/4 neutropenia and febrile neutropenia occurred in 18.4% of patients and in 5.4% of cycles. The incidence of non-hematologic toxicities of grade 3 or worse was asthenia 32.7%, diarrhea 10.2% and peripheral sensory neuropathy 8.2%. Conclusion Docetaxel at 75 mg/m² is active against AGC as second-line chemotherapy after prior exposure to F and P combination chemotherapy. The toxicity profile is moderate.     

Phase II study of docetaxel and cisplatin combination chemotherapy in metastatic gastric cancer

Purpose: Docetaxel, as a single agent, has demonstrated activity in patients with advanced gastric cancer and cisplatin has shown lack of overlapping toxicities with docetaxel. Therefore, we conducted a phase II study to assess the efficacy and the toxicity of a combination regimen of docetaxel plus cisplatin in patients with advanced gastric cancer who have never been treated with palliative chemotherapy. Methods: Ninety-two patients with metastatic gastric cancer were enrolled from April 2000 to March 2004. Patients with histologically confirmed gastric adenocarcinoma, at least one bi-dimensionally measurable lesion, no prior palliative chemotherapy and at least 6 months from the end of adjuvant chemotherapy were eligible for study entry. Docetaxel 75 mg/m² and cisplatin 75 mg/m² were given on day 1. The cycle was repeated every 3 weeks. The objective response was evaluated after three cycles of chemotherapy. Toxicity was assessed according to the National Cancer Institute common toxicity criteria scale version 2.0. Results: In total, 401 cycles were administered, with a median of 5 cycles per patient (range 1–9 cycles). The median age was 56 years (range 31–76). Eighty-six patients were evaluable for treatment response. The objective response rate was 43.5% (95% CI, 33.4–53.6) with one complete response and 39 partial responses. Twenty patients (21.7%) had stable disease and 26 patients (28.3%) had a progression. The median time to progression was 7.0 months (95% CI, 5.0–9.0) and the median overall survival was 11.5 months (95% CI, 9.5–13.4). The chemotherapy was generally well tolerated and the most common grade 3–4 toxicities were neutropenia (17.4%), nausea/vomiting (13.0%) and diarrhea (7.6%). Conclusion: The combination chemotherapy of docetaxel with cisplatin in advanced gastric cancer was tolerable for most patients and showed a promising antitumor activity as a first-line therapy.Keon Woo Park and Jin Seok Ahn contributed equally to this work.     

Gemcitabine plus docetaxel as first-line chemotherapy in patients with advanced non-small cell lung cancer: a lung cancer Galician group phase II study

Background Numerous phase II and III clinical trials have demonstrated a higher activity of combined gemcitabine plus docetaxel schedules against non-small cell lung cancer (NSCLC) than that of both agents in monotherapy. Methods This phase II study evaluated a 3-week based schedule of docetaxel 85 mg/m² (1-h i.v. infusion, d8) combined with gemcitabine 1,000 mg/m² (30-min i.v. infusion; d1,8) as first-line chemotherapy for patients with advanced NSCLC. Results Forty-one patients with non-resectable, stage IIIB/IV, and bidimensionally measurable disease were enrolled. A total of 182 chemotherapy cycles (median 6, range 1–6) was administered to 40 patients during the study; one patient did not receive chemotherapy due to a protocol deviation. Two patients were not evaluable for treatment efficacy. The overall response rate found was 44% (95% CI, 29–59%): three patients (7%) had a complete response and 15 patients (37%) had a partial response (median duration of response = 4.0 months). With a median follow-up of 8.7 months, the median time to disease progression was 4.4 months and the median overall survival was 7.3 months. The combined gemcitabine plus docetaxel chemotherapy was well tolerated except for pulmonary toxicity. The main grade 3–4 hematological toxicity was neutropenia (28% of patients, 9% of cycles). Two cases of febrile neutropenia were reported. The main grade 3–4 non-hematological toxicity was pulmonary toxicity (23% of patients, 6% of cycles). Conclusion Gemcitabine 1,000 mg/m² on days 1 and 8 in combination with docetaxel 85 mg/m² on day 8 given in 3-week cycles is an active and well-tolerated first-line chemotherapeutic regimen for advanced NSCLC.     

Docetaxel plus cisplatin as second-line therapy in metastatic or recurrent advanced gastric cancer progressing on 5-fluorouracil-based regimen

The purpose of this study was to determine the activity and safety of docetaxel plus cisplatin as second-line chemotherapy for advanced gastric cancer. This trial included patients who had failed first-line chemotherapy with a 5-fluorouracil regimen within 1 year before their enrollment. After registration, patients were treated with docetaxel intravenously at a dose of 60 mg/m2 given over 1 hour followed by cisplatin 60 mg/m2 given over 2 hours. The treatment was continued every 3 weeks until disease progression or unacceptable toxicity was detected. Forty-three patients were registered and 41 were assessable for response. Seven partial responses were observed (17.1% of the "evaluable" patients; 95% confidence interval [CI], 0-29) with a median response duration of 3.9 months. Stable disease was documented in 2 cases (4.9%). The median survival was 5.8 months (95% CI, 3.4-8.3), resulting in a 1-year survival rate of 23%. Tolerance was acceptable, with the main toxicity being neutropenia. The authors conclude that second-line chemotherapy with docetaxel plus cisplatin for advanced gastric cancer is feasible with an acceptable toxicity level.     

Multicenter phase II study of docetaxel plus oxaliplatin combination chemotherapy in patients with advanced gastric cancer: Daegu Gyeongbuk Oncology Group

The present study was conducted to evaluate the efficacy and safety of a combination regimen of docetaxel plus oxaliplatin in patients with advanced gastric cancer. Patients with previously untreated metastatic or recurrent, measurable gastric cancer received intravenous docetaxel 65 mg m(-2) plus oxaliplatin 120 mg m(-2) on day 1 based on a 3-week cycle. Forty-two patients were enrolled in the current study, among whom 39 were assessable for efficacy and all assessable for toxicity. One complete response and 18 partial responses were confirmed, giving an overall response rate of 45.2% (95% confidence interval (CI); 31.7-59.7%). At a median follow-up of 7.7 months, the median time to progression and median overall survival was 5.7 (95% CI; 4.3-7.2) months and 9.9 (95% CI; 7.8-12.0) months, respectively. Grade 3/4 neutropenia occurred in 11 patients (26.1%) and febrile neutropenia was observed in four patients (9.5%). The common non-haematologic toxicity was fatigue (grade 1/2, 61.9%) and nausea (grade 1/2, 47.7%). The combination of docetaxel and oxaliplatin was found to be well tolerated and effective in patients with advanced gastric cancer.     

Phase II Study of Irinotecan plus Leucovorin and Bolus 5-Fluorouracil as First- or Second-Line Chemotherapy in Patients with Advanced Gastric or Esophageal-Gastric Junction Adenocarcinoma

Abstract

The aim of this study was to evaluate the activity and safety of 5-fluorouracil (5-FU) / leucovorin (LV) and irinotecan as first- or second-line treatment in patients with advanced gastric adenocarcinoma. Treatment consisted of irinotecan 80 mg/m² intravenously (i.v.), followed by LV 200 mg/m² (i.v.) and 5-FU 450 mg/m² as an i.v. bolus, administered weekly for 6 weeks, followed by a 2-week rest period. Thirty-one patients (23 chemo-naïve, 8 chemo-exposed) were enrolled. The overall response rate was 22.6% and the disease control rate was 38.7%. Among the patients who received the regimen as first-line treatment, objective response rate was 30.4% and the disease control rate was 52.1%. However, progression of the disease was recorded in all the patients receiving the combination as second-line chemotherapy. The median time to disease progression (TTP) was 4 months and the median duration of survival was 7 months. The median TTP was 6 months for patients treated with first-line chemotherapy and 2.5 for those who received study treatment as second line. Furthermore, the median survival duration was 8 months and 6 months, respectively. The most frequent grade 3 toxicity was febrile neutropenia. Grade 3 non-hematological toxicities were rare. There were no treatmentrelated deaths.

The combination of 5-FU/LV and irinotecan as first-line treatment was found to be well tolerated and effective in patients with advanced gastric cancer. Further investigation would be worthwhile, particularly in elderly or debilitated patients who cannot tolerate aggressive chemotherapy.     

A phase II study of docetaxel and oxaliplatin combination in recurrent gastric cancer patients after fluoropyrimidine and/or cisplatin adjuvant treatment: a Korean Cancer Study Group Protocol ST06-02

Background

Surgery alone is no longer an adequate standard of care for patients with resectable gastric cancer. Thus, research efforts should focus on which regimens are the most effective for patients with recurrent gastric cancer after combined treatment with surgery and perioperative or adjuvant chemotherapy.

Methods

Patients with histologically confirmed and measurable advanced gastric cancer who showed a relapse even after fluoropyrimidine and/or cisplatin-based adjuvant chemotherapy received docetaxel (35?mg/m²) intravenously on day 1 and 8 plus oxaliplatin (100?mg/m²) intravenously on day 1 every 3?weeks until disease progression or unacceptable toxicity.

Results

A total of 34 patients with relapsed advanced gastric cancer who had received adjuvant chemotherapy with fluoropyrimidine and/or cisplatin for a median of 6?months (range, 1–48?months) were enrolled in this trial; 22 (64.7?%) patients had been exposed to both agents. Their median age was 58?years (range, 50–68?years). The overall response rate was 55.9?% (95?% confidence interval (CI), 38.3–73.5?%), including 1 complete response and 18 partial responses. At a median follow-up duration of 28.5?months (range, 9.2–50.7?months), the median progression-free survival for all patients was 5.3?months (95?% CI, 4.4–6.1?months) and the median overall survival was 13.8?months (95?% CI, 11.1–16.4?months). The most common grade 3 or 4 hematologic and nonhematologic toxicities were neutropenia (47.1?%) and diarrhea (17.6?%), respectively. Five patients (14.7?%) experienced febrile neutropenia.

Conclusions

Docetaxel and oxaliplatin combination chemotherapy was active and tolerable in patients with recurrent gastric cancer after fluoropyrimidine and/or cisplatin-based adjuvant chemotherapy.     

Sequential doxorubicin and docetaxel as first-line treatment in metastatic breast cancer: a GEICAM-9801 phase II study

Purpose. To evaluate the efficacy and the toxicity profile of the sequential administration of doxorubicin and docetaxel as first-line chemotherapy in metastatic breast cancer (MBC). Patients and methods. Eighty-one patients received a total of 436 cycles of chemotherapy: 236 of doxorubicin (75 mg/m²) and 200 of docetaxel (100 mg/m² every 21 days). The first 35 patients received doxorubicin every 14 days with G-CSF support, and in the other 46 cases doxorubicin was administered every 21 days without G-CSF. Results. After entire treatment the overall response rate was 65% (18 complete responses). With a median follow-up of 19 months (range, 1–48 months), the median time to progression was 11.3 months and the median survival time was 31 months. As expected, febrile neutropenia was the most important toxicity and it appeared in 26 cycles (6%) and 19 patients (23%). In the patients that received doxorubicin every 14 days, the febrile neutropenia incidence was higher during docetaxel treatment, especially after its first administration. Conclusions. The dose and schedule of doxorubicin and docetaxel used in this trial seems to be active in first-line treatment of patients with MBC. The toxicity profile appears to be better than observed with concomitant schedules.     

Docetaxel plus epirubicin is a highly active, well-tolerated, first-line chemotherapy for metastatic breast cancer: results of a large, multicentre phase II study

Purpose In this multicentre phase II study, the efficacy and safety profile of the combination of docetaxel and epirubicin as first-line chemotherapy for metastatic breast cancer (MBC) were evaluated.Methods Epirubicin (75 mg/m²) and docetaxel (75 mg/m²) were given intravenously once every 3 weeks for six cycles to 133 patients with MBC.Results The overall clinical response rate was 67% (complete and partial responses were 23% and 44%, respectively). The median time to progression was 10.8 months (95% CI 9.7–12.6) and the median overall survival was 19.5 months. Granulocyte colony-stimulating factor support was administered to 32% of patients and in 22% of cycles. Grade 3/4 neutropenia occurred in 35% of patients and febrile neutropenia in 19%. The most frequent grade 3/4 non-haematological toxicities (as percent of patients) were asthenia (6%), vomiting (5%) and nausea (5%). No patients developed congestive heart failure.Conclusions The combination of docetaxel and epirubicin was highly active as first-line treatment for MBC and showed a manageable toxicity profile.     

Phase II trial of biweekly paclitaxel plus infusional 5-fluorouracil and leucovorin in patients with advanced or recurrent inoperable gastric cancer

Purpose  To investigate the efficacy and safety of combination chemotherapy with biweekly paclitaxel plus infusional 5-fluorouracil and leucovorin in the treatment of patients with advanced or metastatic gastric cancer. Patients and methods  Chemonaive patients with histologically confirmed advanced or recurrent inoperable gastric cancer were enrolled in the present study. Treatment consisted of paclitaxel (75 mg/m²) and leucovorin (40 mg/m²) as a 2-h intravenous infusion, followed by 5-fluorouracil (2,400 mg/m²) as a 46-h continuous infusion. Cycles were repeated every 2 weeks. Results  Thirty patients were enrolled in this study. There were 12 partial responses, giving an overall response rate of 40.0%. At a median follow-up of 10.6 months, the median time to progression and median overall survival were 3.9 and 8.8 months, respectively. The most common hematological toxicity was grade 1–2 anemia, which was seen in 83.3% of patients. No grade 4 leukopenia, thrombocytopenia, or anemia was noted. The most common non-hematological toxicity was anorexia, which was seen in 70% of patients, although grade 3 anorexia was noted in only 10% of cases. There was no severe treatment-related morbidity or death. Conclusion  Combination chemotherapy consisting of biweekly paclitaxel plus infusional 5-fluorouracil and leucovorin was effective and well tolerated in patients with advanced gastric cancers.     

New systemic frontline treatment for metastatic colorectal carcinoma

Options for first-line chemotherapy in patients with metastatic colorectal carcinoma have broadened considerably with the introduction of irinotecan and oxaliplatin. Furthermore, the oral fluoropyrimidine capecitabine has demonstrated efficacy in Phase III trials and recently was approved for first-line treatment in Europe and the United States. Capecitabine yielded similar median times to disease progression and median survival rates compared with bolus 5-fluorouracil (5-FU)/leucovorin (LV) (Mayo Clinic/North Central Cancer Treatment Group regimen), with superior and similar response rates, respectively. However, its role as a first-line, single-agent substitute for intermittent infusional 5-FU/LV remains to be defined. The addition of irinotecan or oxaliplatin to 5-FU/LV resulted in improved response rates and progression-free survival in large, randomized trials; moreover, irinotecan-containing regimens resulted in improved overall survival. Prevalent regimens of irinotecan/5-FU/LV and oxaliplatin/5-FU/LV have been compared in two randomized Phase III trials. One study demonstrated the statistical superiority of oxaliplatin/infusional 5-FU/LV over irinotecan/bolus 5-FU/LV in terms of response, time to disease progression, and median survival; however, those advantages may have been attributable to infusional administration or to major differences in second-line therapy. A randomized Phase III study comparing irinotecan and oxaliplatin in combination with the same infusional 5-FU/LV regimens and crossover in case of disease progression showed equivalent efficacy for both schedules in the first-line setting, but the irinotecan combination proved beneficial in terms of safety. New molecular targeted agents, such as angiogenesis-modulating compounds (e.g., bevacizumab) and epidermal growth factor receptor inhibitors (e.g., cetuximab), are under clinical investigation. This review updates current systemic frontline treatments and future perspectives for patients with advanced colorectal carcinoma.     

Docetaxel plus oxaliplatin with or without fluorouracil or capecitabine in metastatic or locally recurrent gastric cancer: a randomized phase II study

BackgroundDocetaxel/cisplatin/infusional 5-fluorouracil (5-FU; DCF) is a standard chemotherapy regimen for patients with advanced gastric cancer (GC). This phase II study evaluated docetaxel/oxaliplatin (TE), docetaxel/oxaliplatin/5-FU (TEF), and docetaxel/oxaliplatin/capecitabine (TEX) in patients with advanced GC.Patients and methodsPatients with metastatic or locally recurrent gastric adenocarcinoma (including carcinoma of the gastro-oesophageal junction) were randomly assigned (1 : 1 : 1) to TE, TEF, or TEX. Each regimen was tested at two doses before full evaluation at optimized dose levels. The primary end point was progression-free survival (PFS). Overall survival (OS), tumour response, and safety were also assessed. A therapeutic index (median PFS relative to the incidence of febrile neutropenia) was calculated for each regimen and compared with DCF (historical data).ResultsOverall, 248 patients were randomly assigned to receive optimized dose treatment. Median PFS was longer with TEF (7.66 [95% confidence interval (CI): 6.97–9.40] months) versus TE (4.50 [3.68–5.32] months) and TEX (5.55 [4.30–6.37] months). Median OS was 14.59 (95% CI: 11.70–21.78) months for TEF versus 8.97 (7.79–10.87) months for TE and 11.30 (8.08–14.03) months for TEX. The rate of tumour response (complete or partial) was 46.6% (95% CI 35.9–57.5) for TEF versus 23.1% (14.3–34.0) for TE and 25.6% (16.6–36.4) for TEX. The frequency and type of adverse events (AEs) were similar across the three arms. Common grade 3/4 AEs were fatigue (21%), sensory neuropathy (14%), and diarrhoea (13%). Febrile neutropenia was reported in 2% (TEF), 14% (TE), and 9% (TEX) of patients. The therapeutic index was improved with TEF versus TEX, TE, or DCF.ConclusionThese results suggest that TEF is worthy of evaluation as an arm in a phase III trial or as a backbone regimen for new targeted agents in advanced GC.ClinicalTrials.gov IdentifierTrial registration number: NCT00382720.     

A randomised phase II study of docetaxel/oxaliplatin and docetaxel in patients with previously treated non-small cell lung cancer: an Alpe-Adria Thoracic Oncology Multidisciplinary group trial (ATOM 019)

Introduction

To date, no combination regimen has proven superior to single agent chemotherapy as a second-line treatment for non-small cell lung cancer (NSCLC).

Methods

This multicenter, non-comparative randomised phase II trial evaluated the activity of docetaxel (75 mg/m² on day 1) with oxaliplatin (70 mg/m² on day 2) every 3 weeks in previously treated NSCLC patients; the reference arm was single-agent docetaxel (75 mg/m² on day 1 every 3 weeks). It was designed as a one-stage, three-outcome phase II trial; 21 evaluable patients were required in each arm. The primary end-point was response rate; secondary end-points were toxicity, progression free survival (PFS) and overall survival.

Results

Fifty patients were enrolled. Patient characteristics included male/female, 76/24%; median age 62 years; ECOG PS 0/1, 36/64%; previous platinum-based chemotherapy, 98%. Partial response was seen in 20% and 8%, stable disease in 52% and 32%, of patients treated with docetaxel/oxaliplatin and docetaxel, respectively. Main grade 3-4 toxicities were neutropenia 56% and 64%; febrile neutropenia 4% and 8%; diarrhoea 12% and 4% for docetaxel/oxaliplatin and docetaxel, respectively. Median PFS was 5.0 and 1.7 months, median survival 11.0 and 7.1 months, and 1-year survival 44% and 32% for docetaxel/oxaliplatin and docetaxel, respectively.

Conclusions

The study met its pre-defined study end-point; docetaxel/oxaliplatin and more generally platinum-containing doublets warrant further evaluation as second-line therapy for patients with NSCLC.     

Treatment outcomes of oxaliplatin, 5-FU, and leucovorin as salvage therapy for patients with advanced or metastatic gastric cancer: a retrospective analysis

Purpose  We performed a single-institution retrospective study to evaluate the efficacy and toxicities of oxaliplatin, 5-fluorouracil (5-FU), leucovorin (LV) combination chemotherapy as salvage treatment in patients with metastatic or advanced gastric cancer. Methods  Sixty-two patients with advanced gastric cancer previously treated were eligible for the study. Patients received oxaliplatin 100 mg/m² and LV 100 mg/m² (2-h intravenous infusion) followed by 5-FU 2,400 mg/m² (46-h continuous infusion) every 2 weeks, and responses were assessed after every three cycles. Results  Fifty-nine out of 62 patients were assessable for response. Among them, 46 patients had previously been treated with cisplatin based chemotherapy. Patients had a median age of 57 years (range 32–76 years), 72.6% had an Eastern Cooperative Oncology Group performance status of 0 or 1. Total 296 courses of chemotherapy were administered as second-line (67.7%) or third-line (27.4%), and the median courses per patient was three cycles. Out of 59 evaluable patients, 14 partial responses were observed (overall response rate, 22.6%). Stable disease was observed in 22 patients (35.5%), and progressive disease in 23 patients (37.1%). The median response duration, time to progression, and overall survival were 2.3, 3.0, and 8.0 months, respectively. The major toxicities were neutropenia, mucositis, and peripheral neuropathy. Grade 3 or 4 hematologic toxicities included neutropenia in nine patients (14.5%) and thrombocytopenia in one patient (1.6%). Other grade 3 or 4 toxicities included mucositis in one patient (1.6%) and vomiting in two patients (3.2%). Grade 1 or 2 peripheral neuropathy were observed in 18 patients (29.0%), however there were no cases of grade 3 or 4 peripheral neuropathy and no treatment-related deaths. Conclusion  The combination of oxaliplatin, 5-FU and LV was effective and safe salvage chemotherapy in advanced gastric cancer patients.     

多西紫杉醇联合奥沙利铂和5-氟尿嘧啶双周方案治疗晚期胃癌的初步研究

目的 探讨多西紫杉醇(DOC)联合奥沙利铂(L-OHP)和5-氟尿嘧啶(5-Fu)的DOF双周方案对晚期胃癌的临床疗效和毒副反应.方法 37例晚期胃癌患者均行锁骨下深静脉穿刺或外周肘正中静脉穿刺,置入单腔输液导管,经电脑输液泵控制5-Fu的输液速度.DOC 35 mg/m2, 静脉滴注1 h,第1天;L-OHP 85 mg/m2,静脉滴注2 h,第1天;甲酰四氢叶酸(LV) 200 mg/m2,静脉滴注2 h,第1天;5-Fu 1500 mg/m2,持续静脉滴注48 h,第1～2天.14 d为1个周期,至少应用3个周期进行疗效评估.结果 全组37例均可评价疗效,总有效率为67.6%,其中完全缓解率为27.0%,部分缓解率为40.5%.至肿瘤进展时间为9.2个月,中位生存期为13.7个月.在初次化疗的11例患者中,有效率为81.8%;在既往接受过化疗的26例患者中,有效率为61.5%.主要剂量限制性毒性反应为骨髓功能抑制,其中Ⅲ～Ⅳ度白细胞下降率为29.7%,无治疗相关性死亡. 结论 DOF双周方案是晚期胃癌的有效化疗方案,其毒副反应轻微,患者易于耐受,值得进一步研究.     

The efficacy and safety of reduced-dose docetaxel,cisplatin, and 5-fluorouracil in the first-line treatment of advanced stage gastric adenocarcinoma

Patients with advanced gastric carcinoma have still had bad prognosis despite advances in the modern treatment era. Docetaxel, cisplatin, 5-fluorouracil (DCF) is effective, but highly toxic regimen for advanced cases. In this study, we modified the standard doses of DCF (mDCF) to evaluate the effectiveness and side effects. From July 2005 to July 2008, 37 advanced gastric cancer patients treated with at least one course of mDCF protocol as first-line treatment were included. The mDCF protocol included 60 mg/m² docetaxel and cisplatin for 1 day and 600 mg/m²/day, 5-flourouracil infusion for 5 days, repeated every 3 weeks. No patients used prophylactic granulocte -colony stimulating factor. Of the patients, 28 were male and nine were female; the median age was 53 (23–65) years. Of them, 83.8% received at least four courses of chemotherapy and 64.9% completed the preplanned six courses of treatment. Eleven (29.7%) of those patients who received mDCF in the first-line treatment used the FOLFIRI (5-FU, folinic acit, irinotekan) regimen for the second-line treatment. Response rates were evaluated according to RECIST criteria in 30 out of 37 patients. The median follow-up time was 7.1 months. The longest follow-up time was 19.9 months. Two patients (5.4%) had complete response, nine (21.6%) had partial response, and 14 (37.9%) had stabilized disease; overall, the disease was controlled in 25 patients (64.9%) whereas five patients (13.5%) had progression. Median time to progression was 6.7 months and overall survival was 10 months. The assessment of patients for grade 3–4 toxicity revealed that while 5.4% had anemia and 8.1% had neutropenia, 5.4% nausea and 5.4% diarrhea. Neutropenic fever developed in two patients, requiring hospitalization. G-CSF was used in three patients. Two patients with neutropenic fever and two with severe anemia (total number 4; 10.8%) received delayed chemotherapy. Dose reduction was required in four patients (10.8%), one due to neutropenia, one due to nephrotoxicity, and two due to nausea. No patient died due to chemotherapy toxicity. This retrospective study suggested that mDCF might have comparable efficacy with classical DFC, with better toxicity profile. However, its small size and retrospective nature should be considered when interpreting the results.     

Docetaxel, 5-fluorouracil, and leucovorin as treatment for advanced gastric cancer: results of a phase II study

Background: Previous studies have shown that the taxane, docetaxel, is effective in treating gastric cancer. The aim of this study was to assess the efficacy and safety of docetaxel in combination with 5-fluorouracil (5-FU) and leucovorin (LV). Methods: Thirty patients with histologically proven locally advanced and/or metastatic gastric cancer with WHO performance status 0–2 were enrolled and received either 75 or 100 mg/m² docetaxel as a 1-h intravenous infusion on day 1 every 28 days. All patients also received 5-FU (1800 mg/m²) plus LV (500 mg/m²), by continuous intravenous infusion over 24 h on days 1, 8, and 15 every 28 days. Chemotherapy was given for at least two cycles. Results: Of the 25 evaluable patients, 3 showed a complete response, 4 showed a partial response, and 11 patients had stable disease. The overall response rate was 28.0% (95% confidence interval [CI], 10.4, 45.6). The median time to progression was 5.9 months (95% CI, 5.4, 6.5), and the median overall survival was 7.7 months (95% CI, 7.2, 8.3) for the intent-to-treat population. The most frequent grade III and IV hematological toxicities were neutropenia and anemia. Febrile neutropenia was observed in 10% of patients and 2.4% of cycles. The prophylactic use of granulocyte colony-stimulating factor (G-CSF) in 3 patients reduced the incidence and severity of neutropenia. Other hematological toxicities were rare. Conclusion: Docetaxel in combination with weekly 5-FU and LV is effective in treating patients with advanced/metastatic gastric cancer. This new docetaxel-containing combination shows promise as a third-generation treatment option for gastric cancer. Received: December 25, 2001 / Accepted: April 22, 2002 Offprint requests to: M. Constenla     

多西他赛、氟脲嘧啶分别联合奥沙利铂或顺铂治疗进展期胃癌的临床对照观察

目的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5d联合方案一线治疗进展期胃癌的有效性和安全性。方法75例病人分为A，B两组。A组38例，接受DOF方案治疗。DOF方案：多西他赛75mg／m^2，d2，奥沙利铂130mg／m^2，d1，氟脲嘧啶500mg／m2，d1-d5；B组37例，接受DCF方案治疗。DCF方案：多西他赛75mg／m^2，d2，顺铂25mg／m^2，dl-d3，氟脲嘧啶500mg／m^2，dl-d5。均每3wk重复，至少应用2周期。结果A组病人临床控制率、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1a生存率和2a的生存率分别为65．78％、5．26％、42．10％、5．9mo、11．2mo、52．63％、18．42％。B组分别为54．06％、2．70％、35．14％、5．8mo、10．8mo、48．64％、13．51％。治疗前两组生活质量（QOL）分值相当，但是治疗后1mo、2mo的QOL分值似有差异，但两组有效率与生存期比较差异并无显著性（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病人生存期，提高生活质量。特别是前者对生活质量的影响比后者轻。     

晚期结直肠癌内科治疗进展

晚期转移性结直肠癌的5年生存率低于10％。5-FU／LV方案治疗的中位生存期大约12个月。最近化疗方案的更新延长了患者的中位生存期。研究发现奥沙利铂、伊立替康联合5-FU／LV或者卡培他滨等化疗方案使中位生存期延长到20个月。奥沙利铂，伊立替康联合5-FU／LV比传统的单药5-FU／LV使生活质量改善时间延长。目前转移性结直肠癌标准的一线治疗方案为FOLFOX和FOLFIRI。正在进行的研究关注新的分子靶向药物（molecular targeted therapy）联合化疗治疗转移性结直肠癌，且部分试验取得了较好的疗效。本文将对5-FU、新一代化疗药物以及分子靶向药物在转移性结肠癌治疗的演进及新进展作一综述。