A phase II study of paclitaxel combined with infusional 5-fluorouracil and low-dose leucovorin for advanced gastric cancer

Purpose The aim of this study was to investigate the efficacy and safety of the combination chemotherapy of paclitaxel, infusional 5-fluorouracil (5-FU) and leucovorin (FLT regimen) in advanced gastric cancer. The primary end point was the time to progression (TTP). Methods Patients with evaluable disease with or without measurable lesions received 175 mg/m² paclitaxel on day 1 followed by 20 mg/m² leucovorin and 24-h infusion of 5-FU 1,000 mg/m² (day 1-3) repeated every 3 weeks. Results Sixty patients were enrolled. The median TTP and overall survival duration were 13 and 60 weeks, respectively. One-year survival rate was 53.3%. Of the 50 patients with measurable lesion, the overall response rate was 31.7%. The most common grade 3–4 adverse event was neutropenia (61.7%). Conclusion The FLT regimen showed an efficacy comparable to other regimens of cisplatin or anthracycline combinations with the advantage of remarkably low non-hematological toxicity. These data about the efficacy of this regimen need confirmation in a phase III trial.     

A multicentre randomised trial comparing weekly paclitaxel + S-1 with weekly paclitaxel + 5-fluorouracil for patients with advanced gastric cancer

PurposeThis study aimed to compare the efficacy and toxicity of weekly paclitaxel plus S-1 with weekly paclitaxel plus 5-fluorouracil in treating advanced gastric cancer as first line regimen. The primary end-point was disease control rate (DCR).MethodsPatients with advanced or recurrent gastric cancer were randomly assigned to an experimental arm or a control arm. The experimental arm’s dosage schedule was paclitaxel 60 mg/m² (intravenous infusion) on days 1, 8 and 15 and S-1 80–120 mg/d (oral administration) on days 1–14. Control arm patients were given the same paclitaxel, combined with 5-fluorouracil 500 mg/m² (continuous intravenous infusion) on days 1–5; and leucovorin 20 mg/m² (intravenous infusion) on days 1–5. All schedules were repeated every 28 d.ResultsA total of 240 patients were enrolled and equally randomised into two arms. The overall response rate and DCR of the experimental arm was non-inferior to that of the control arm both in the per-protocol set and the full analysis set. The secondary end-point median progression-free survival (PFS) of the experimental and control arms was 153 and 129 d, with the hazard ratio of 0.641 (95% CI: 0.473–0.868, P = 0.004). The hazard ratio of the time to treatment failure of the two arms was 1.449 (95% CI: 0.705–2.980, P = 0.229). The six-month PFS rates of both arms were similar (31.3% versus 31.8%, P = 0.94). Cox regression analysis indicated that only treatment regimen and age were independent predictive factors for PFS. The most common adverse events were haematological and gastrointestinal. The rates of grade 3–4 adverse events were not significantly different between the two study arms and were mostly lower than 5%.ConclusionWeekly paclitaxel combined with S-1 is an active and well-tolerated regimen, supporting the view that S-1 can be an alternative for infusional 5-fluorouracil for advanced gastric cancer.     

A multicenter phase II study of biweekly paclitaxel and S-1 combination chemotherapy for unresectable or recurrent gastric cancer

Purpose  This Phase II study assessed the activity and safety of biweekly paclitaxel and oral S-1 as treatment for unresectable and recurrent gastric cancer. The maximum tolerated dose for this regimen had been established previously in a Phase I study performed in Japanese patients. Patients and methods  Chemotherapy was performed using two anticancer agents, S-1 and paclitaxel. Oral S-1 (80 mg/m²) was administered twice a day after meals for two consecutive weeks from Day 1 to 14, followed by a 2 week recovery period; paclitaxel (120 mg/m²) was administered intravenously, biweekly, on Days 1 and 15. The patient received cycles of this regimen every 4 weeks (q 28-day cycles). The primary end point was the response rate according to the Response Evaluation Criteria in Solid Tumors. Results  A total of 39 patients (median age, 65 years) were enrolled; 13 other patients were screened, but found to be ineligible. All patients had unresectable and recurrent gastric cancer. The most common treatment-related Grade 3/4 adverse events were neutropenia (37.5%), appetite loss, diarrhea, decreased sodium (each 5%), and anemia, increased alanine aminotransferase, general fatigue, and dizziness (each 2.5%). Almost all the patients experienced alopecia. Intent-to-treat analysis showed a response rate of 43.6%. With a median follow-up of 14 months (range 8–21 months), median survival was 256 days and the median time to progression was 4 months. Conclusion  A combination regimen of biweekly paclitaxel and oral S-1 was well tolerated and showed promising activity against unresectable and recurrent gastric cancer.     

Paclitaxel in combination with weekly 24-hour infusional 5-fluorouracil plus leucovorin in the second-line treatment of metastatic breast cancer: Results of a phase II study

Purpose: To evaluate the antitumor activity in terms of response rate (RR), time to progression (TTP) and survival of paclitaxel in combination with weekly 24-hour infusional 5-fluorouracil (5-FU)/leucovorin in pretreated metastatic breast cancer (MBC).Patients and methods: Fifty-four patients with bidimensionally measureable disease were included during phase II. Thirty-two had anthracycline resistant disease. Treatment consisted of 5-FU (24-hour i.v. infusion) 2.0 g/m², leucovorin (two-hour i.v. infusion prior to 5-FU) 500 mg/m², weekly for six weeks (day 1, 8, 15, 22, 29, 36) and paclitaxel (three-hour i.v. infusion) 175 mg/m² was administered additionally on days 1 and 22, q 50 days.Results: We observed complete remissions in 4% of patients (2 of 54), partial remissions in 55% (30 of 54), stable disease in 37% (20 of 54) and progressive disease in 4% (2 of 54). The overall RR was 59% (95% CI 48%–72%). The RR in 32 patients with anthracycline resistant disease was 59% (19 of 32). The median duration of response was 12 months (3–22), median TTP eight months (2–22) and median survival time 15 months (2–28). Neutropenia was common, but of CTC grade 2 or 3 in most patients. Nonhematologic toxicities mostly consisted of CTC grade 1 and 2 myalgia, diarrhea, mucosits, nausea and vomiting.Conclusions: Paclitaxel combined with weekly 24-hour infusional 5-FU/leucovorin is well tolerated in the second line treatment of MBC. High efficacy was documented even in the treatment of anthracycline resistant disease, which warrants further evaluation.     

Phase I/II trial of combination therapy with S-1 and weekly paclitaxel in patients with unresectable or recurrent gastric cancer

Purpose  We aimed to examine the safety and antitumor effects of a combination of S-1 and paclitaxel in patients with unresectable or recurrent gastric cancer in a phase I/II setting. Patients and methods  The study was designed as a phase I/II clinical trial. In phase I portion, the dose of paclitaxel was escalated to estimate the maximum-tolerated dose (MTD) and recommended dose (RD) of paclitaxel with fixed dose of S-1. S-1 (daily dose, 80 mg/m²) was given orally on days 1–21 every 35-day cycle (rest on days 22–35). Paclitaxel was administered intravenously on days 1, 8 and 15, at an initial dose of 40 mg/m², stepping up to 70 mg/m² in 10-mg/m² increment. Dose-limiting toxicity (DLT) was defined as grade 4 hematological toxicity, grade 3 or higher nonhematological toxicity, and treatment discontinuation due to adverse reactions during the first course of treatment. In phase II portion, the efficacy and toxicity at the RD of paclitaxel with S-1 were assessed. Results  The MTD of paclitaxel was estimated to be 60 mg/m², because >33.3% of patients (2/3) developed DLTs. DLT included postponement of treatment due to grade 2 neutropenia, and grade 3 stomatitis, anorexia, and nausea. Therefore, the RD of paclitaxel was estimated to be 50 mg/m². In the phase II portion, 22 patients were evaluated with 50 mg/m² paclitaxel and 80 mg/m² S-1 in a 35-day cycle. The response rate was 54.5% (95% CI, 32.2–75.6%). The median survival time was 283 days (95% CI, 218–508 days). The median number of treatment courses was 4 (range 1–10), indicating that this regimen could be given repeatedly. Conclusions  This phase I/II trial of combination therapy with S-1 and paclitaxel in patients with unresectable or recurrent gastric cancer showed that this regimen has substantial antitumor activity and can be given safely.     

A Phase II Trial of Etoposide,Leucovorin and 5-Fluorouracil (ELF) in Patients with Advanced Gastric Cancer

Abstract

Etoposide, leucovorin and 5-fluorouracil (ELF) chemotherapy has been reported to be less toxic yet effective (response rates of 50%) in patients with advanced gastric cancer. A phase II study of ELF in 25 patients (11 males, 14 females, median age 53 years) with advanced adenocarcinoma of the stomach is reported. Patients received outpatient intravenous etoposide 120mg/m² over 2 hours, folinic acid 300mg/m² over 2 hours, 5-fluorouracil 500 mg/m² boluses daily for 3 days every 21 days. Of 17 measurable patients, there was one complete response (CR), 4 partial responses (PR) for a total response rate of 29.4%. Non-hematologic toxicity was modest (grade 0 vomiting 11/21, stomatitis 16/21, diarrhea 17/21). Grade 3/4 neutropenia was seen in 14/23, thrombocytopenia in 2/23, anemia in 5/23 patients. Median progression-free and overall survival was 4.1 and 7.1 months, respectively. In conclusion, ELF chemotherapy shows only modest activity in patients with advanced gastric cancer and is associated with severe hematologic toxicity.     

Phase II study of 5-fluorouracil and paclitaxel in patients with gemcitabine-refractory pancreatic cancer

Purpose  There is no effective salvage regimen for failed gemcitabine-based chemotherapy. This study evaluated the efficacy and toxicity of 5-fluorouracil and paclitaxel in patients with gemcitabine-refractory pancreatic cancer. Methods  Between January 2004 and December 2007, 28 patients with pancreatic cancer previously treated with gemcitabine-based chemotherapy were enrolled. 5-Fluorouracil 1,000 mg/m² was infused (days 1, 2, and 3) and paclitaxel 175 mg/m² (day 1) was administered every 4 weeks. The primary endpoint of this study was efficacy and toxicity and the secondary endpoint was time to progression and overall survival. Results  A total of 75 cycles were given, for a mean of 2.68 cycles per patient. The response could be evaluated in 20 patients. Two patients (10%) obtained a partial response, and four patients (20%) had stable disease. The median time to progression and overall survival was 2.5 and 7.6 months, respectively. Grade 3/4 hematological toxicity included neutropenia in six patients (21.4%), anemia in one (3.6%), and thrombocytopenia in one (3.6%). One (3.6%) patient experienced grade 4 neuropathy, and two (7.2%) patients experienced grade 3 diarrhea. Conclusion  The 5-fluorouracil and paclitaxel combination treatment seems to be effective in patients with advanced pancreatic cancer that did not respond to a gemcitabine-based regimen.     

Weekly Taxotere and cisplatin with continuous-infusion 5-fluoruracil for the treatment of advanced gastric and esophageal cancer: a prospective, observational, single-institution experience

Abstract  

The combination of Taxotere (docetaxel), cisplatin, and prolonged-infusion 5-fluorouracil (5-FU) has emerged as an active treatment for advanced gastric cancer. However, the regimen proposed by van Cutsem et al. (J Clin Oncol 24:4991–7, 2006) is associated with significant toxicity and therefore alternative schedules are needed. In the present study, patients with advanced gastric or esophageal cancer received Taxotere 35 mg/m² and cisplatin 25 mg/m² on day 1, followed by 5-FU 180 mg/m²/day as a 7-day prolonged infusion. Drugs were given weekly for 3 consecutive weeks followed by 1 week’s rest. Cycles were repeated every 4 weeks. Overall, a total of 110 cycles were administered to 27 patients (median age 63 years, range 40–78 years). The median number of cycles per patient was 4 (range 2–6). Nine partial responses were obtained, resulting in an overall response rate of 33% [95% confidence interval (CI) 16–51], a median time to progression of 6.4 months (95% CI 5.4–7.4), and a median overall survival of 10.7 months (95% CI 6.6–14.8). Toxicity was mild; grade III-IV neutropenia was the most frequently observed side effect, in 9 administered cycles (8%); neutropenia was complicated by fever in 2 cycles. Other grade III–IV toxicities observed in >5% of patients were anemia and mucositis.     

A phase I study of palliative chemoradiation therapy with paclitaxel and cisplatin for local symptoms due to an unresectable primary advanced or locally recurrent gastric adenocarcinoma

Purpose  To establish the maximum tolerated dose and dose-limiting toxicity of chemoradiation with paclitaxel (PTX) and cisplatin (CDDP) for patients with local symptoms due to unresectable primary advanced or locally recurrent gastric adenocarcinoma located at left-upper abdomen. Methods  Chemotherapy consisted of PTX at escalating doses of 40–80 mg/m² per day and CDDP at escalating doses of 20–25 mg/m² per day on days 1, 15, and 29. Concurrent radiation was administered up to a dose of 45 Gy for 5 weeks. Results  A total of nine patients were enrolled, of which six were into level 1 (PTX 60 mg/m² and CDDP 20 mg/m²) and three into level −1 (PTX 50 mg/m² and CDDP 20 mg/m²). At level 1, one patient developed grade 3 fatigue, and the other experienced grade 5 DIC, grade 5 pneumonia, grade 4 thrombocytopenia, grade 3 hyponatremia, and grade 3 esophagitis as dose-limiting toxicities. A palliative effect was observed in eight of nine patients; six of six patients at level 1 and two of three at level −1. Conclusion  PTX 50 mg/m² and CDDP 20 mg/m² given biweekly with concurrent radiation therapy of 45 Gy were well tolerated.     

A phase II study of combined chemotherapy with methotrexate, 5-fluorouracil, and low-dose cisplatin (MFP) for histologically diffuse-type advanced and recurrent gastric cancer (KDOG9501)

Background Histologically diffuse-type gastric cancer is well known to have a poor prognosis and is often complicated with abdominal and pleural effusions. We evaluated the efficacy of a low dose of cisplatin combined with methotrexate and 5-fluorouracil (MFP therapy) in diffuse-type advanced gastric cancer. Methods The study group comprised 47 patients. Patients with pleural effusion or ascites were actively enrolled. Methotrexate (30 mg/m² per day) plus 5-fluorouracil (600 mg/m² per day) was administered on days 1 and 8. Cisplatin (6 mg/m² per day) was given daily for 14 days after which there was 14 day's rest. Calcium leucovorin (15 mg) was administered after methotrexate. Results The overall response rate was 38.3%. Ascites disappeared or decreased in 15 of 23 patients (disappeared in 9). Pleural effusion disappeared or decreased in 6 of 8 patients (disappeared in 4). Of the 21 patients with poor oral intake at study entry, 15 (71.4%) were able to orally ingest food. Hematologic toxicity of grade 3 or higher comprised leukopenia in 10 patients (21.3%) and neutropenia in 9 (19.1%). Nonhematologic toxicity included anorexia and nausea/vomiting, in 1 patient each (2.1%). The median survival time was 211 days. Conclusion MFP therapy is useful for the management of diffuse-type inoperable and recurrent gastric cancer, even in patients with conditions such as pleural effusion, ascites, or lymphangitis carcinomatosa who have a poor prognosis or cannot eat solid food.     

A phase I combination chemotherapy study of biweekly paclitaxel and S-1 administration in patients with advanced gastric cancer

The aim of the current study was to determine the maximum tolerated dose (MTD) and the dose limiting toxicity (DLT) of a combination of paclitaxel and S-1 in patients with advanced gastric cancer. Fifteen patients were enrolled. The dose for S-1 was set at 80 mg/m²/day (days 1–14), while the dose for paclitaxel increased by 10 mg/m² for every three patients, with a starting dose of 100 mg/m² and was given biweekly on day 1 and 15. There was no severe toxicity (grade 4) recorded in patients receiving up to 120 mg/m² of paclitaxel. Leukopenia/neutrophilia with grade 1 to 3 occurred in six patients up to level 3. At 130 mg/m² of paclitaxel, grade 4 leukocytopenia and neutropenia events and grade 3 diarrhea developed in one out of three patients. One patient in another group of three patients that were enrolled at level 3, developed grade 4 granulocytopenia with fever (a body temperature higher than 38°C) and grade 3 leukocytopenia. Eight patients, out of a total of 15, showed a partial response, resulting in an objective response rate of 53%. Five patients received gastrectomy. Median survival time was 428 days and the 1 year survival rate was 53%. Biweekly paclitaxel/S-1 combination chemotherapy could be safely used for the treatment of advanced gastric cancer. The recommended doses for a phase II study with paclitaxel and S-1 are 120 mg/m² and 80 mg/m², respectively.     

A multiple-center phase II study of biweekly oxaliplatin and tegafur–uracil/leucovorin for chemonaive patients with advanced gastric cancer

Purpose  The current study assessed the efficacy and safety of biweekly oxaliplatin combining oral tegafur–uracil/leucovorin in treating chemonaive patients with advanced gastric cancer. Methods  Eligible patients were 18–75 years old, had stage IV disease or post-surgery recurrence, no prior palliative chemotherapy, and an ECOG performance status of 0–2. Patients in the current study received 2-h i.v. infusion of oxaliplatin at a dose of 100 mg/m² after diluting in 500 mL 5% dextrose/water (dexan premedication), and 5-HT3 antagonist biweekly. Oral tegafur–uracil and leucovorin was given at a dose of 300 mg/m²/day and 60 mg/day three times daily from day 1 to 21, respectively, followed by a 1-week rest. Response assessment was based on the RECIST criteria and was performed every two courses. Toxicity was assessed according to NCI common toxicity criteria version 2. Results  From October 2003 to April 2006, 57 patients were evaluated (55 eligible) with a median age of 61 years (range 31–75). According to the assessment of response in 48 evaluable patients, partial response rate was 24/48 (50.0%) (95% CI: 35.23–64.73%) and stable disease was observed in 11 patients (22.92%), and diseased progressed in 13 patients (27.08%). Mean number of oxaliplatin cycles was 3 (0.5–6.5). Median time to progression was 177 days. Median overall survival was 318 days. Major-grade (III/IV) toxicities were diarrhea 25.5%, vomiting 16.5%, anemia 10.9%, numbness 12.7%, thrombocytopenia 7.3%, neutropenia 3.6% and leucopenia 1.8%. Conclusions  Biweekly, oxaliplatin combining oral tegafur–uracil/leucovorin in treating patients with advanced gastric cancer showed acceptable activity and manageable toxicity. This study was presented in part at the 7th International Conference of the Asian Clinical Oncology Society, September 14–28, 2006, Beijing, China.     

A multi-center phase II study of S-1 plus paclitaxel as first-line therapy for patients with advanced or recurrent unresectable gastric cancer

Purpose  This study was conducted to evaluate the safety and efficacy of S-1 and paclitaxel combination therapy for patients with advanced gastric cancer. Methods  Eligible patients had previously untreated advanced or relapsed gastric cancer with measurable lesion(s) and an ECOG PS of 0-2. Treatment consisted of S-1 35 mg/m² p.o. b.i.d. on days 1–14 followed by a 7-day off plus paclitaxel 70 mg/m² i.v. on days 1 and 8 of a 21-day cycle. Results  Fifty-six patients (M/F = 37/19) were enrolled. The median age was 59 years. The median number of cycles administered was six (range 1–18). Out of the 53 patients evaluated, there was 1 (1.9%) CR, 20 (37.7%) confirmed PRs, 5 (9.4%) unconfirmed PRs, 21 (39.6%) SDs, and 6 (11.3%) PDs. The objective tumor response was 39.6%. The median time to progression was 29 weeks. The median survival was 51 weeks. All 56 patients were assessed for treatment safety. The treatment was well tolerated with grade 3/4 neutropenia in 20%/13%, grade 3 febrile neutropenia in 7%, grade 2/3 diarrhea in 9%/4%, vomiting in 11%/0%, stomatitis in 4%/4%, and neuropathy in 4%/0% of patients. Conclusions  S-1 and paclitaxel combination treatment is an effective regimen with a favorable toxicity profile in patients with advanced gastric cancer.     

Irinotecan combined with 5-fluorouracil and leucovorin third-line chemotherapy after failure of fluoropyrimidine, platinum, and taxane in gastric cancer: treatment outcomes and a prognostic model to predict survival

Background

The aim of this study was to evaluate the activity and safety of the combination chemotherapy of 5-fluorouracil (5-FU), leucovorin, and irinotecan (FOLFIRI regimen) after failure of fluoropyrimidine, platinum, and taxane in gastric cancer (GC) and to evaluate the prognostic factors for survival.

Methods

Patients received biweekly FOLFIRI chemotherapy as third-line treatment. The FOLFIRI-1 consisted of irinotecan (180 mg/m² in a 2-h infusion) on day 1, and then leucovorin (200 mg/m² in a 2-h infusion) and 5-FU (a 400 mg/m² bolus, followed by 600 mg/m² in a 22-h continuous infusion) on days 1 and 2. FOLFIRI-2 consisted of irinotecan (180 mg/m² in a 2-h infusion) on day 1, and then leucovorin (400 mg/m² in a 2-h infusion) and 5-FU (a 400 mg/m² bolus, followed by 2400 mg/m² in a 46-h continuous infusion) on day 1.

Results

A total of 158 patients were included. The overall response rate was 9.6 % in patients with measurable lesions. The median progression-free survival (PFS) and overall survival (OS) were 2.1 months [95 % confidence interval (CI), 1.7–2.5] and 5.6 months (95 % CI, 4.7–6.5), respectively. The major grade 3/4 toxicity was myelosuppression (36.7 %). Good performance status (PS), fewer metastatic sites, and longer duration from the first-line to third-line chemotherapy were independent prognostic factors affecting both PFS and OS.

Conclusions

The FOLFIRI regimen showed antitumor activity and tolerable toxicity profiles against advanced GC in the third-line setting. Patients with good PS, fewer metastatic sites and longer previous treatment duration might have the maximal benefit from third-line chemotherapy.     

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.     

A phase II trial of pemetrexed and gemcitabine as first line therapy for poor performance status and/or elderly patients with stage IIIB/IV non-small cell lung cancer

Pemetrexed and gemcitabine are both active agents for the treatment of locally advanced or metastatic NSCLC. We tested a novel biweekly combination of pemetrexed and gemcitabine for tolerability and efficacy in 45 elderly and/or poor performance status patients (44% female, mean age of 72.4 years) with measurable stage IIIB/IV NSCLC. Patients received biweekly cycles of pemetrexed 500 mg/m² IV over 10 min followed by gemcitabine 1500 mg/m² IV with vitamin B12 1000 μg IM, and folic acid 1 mg po daily beginning 7 days before and continuing throughout treatment (median of 4 cycles). Ten patients experienced grade 3/4 neutropenia, two had grade 3 febrile neutropenia, and two had grade 3 anemia. Patients with ECOG PS 2 appeared poorly suited for the regimen, with 61.5% completing ≤2 cycles. The overall response rate was 17.8%, the clinical benefit rate (CR + PR + SD >24 weeks) was 26.7%, and the median progression free survival was 3.5 months. However, ECOG 0–1 patients had longer PFS and tended to have a better response rate than ECOG 2 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.     

Paclitaxel and gemcitabine combination in a biweekly schedule in patients with advanced non small-cell lung cancer: a phase i study

Purpose: This phase I study was designed to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of the paclitaxel–gemcitabine combination in a biweekly schedule in chemotherapy-naive patients with advanced non small-cell lung cancer (NSCLC). Patients and methods: Treatment was administered on an outpatient basis every 2 weeks: paclitaxel over a 1-h IV infusion and gemcitabine as a 30-min IV infusion immediately following paclitaxel. Results: Twenty-nine patients were treated at six different dose levels, ranging from paclitaxel 135–175 mg/m² and gemcitabine 1,500–3,000 mg/m². A total of 198 cycles were administered (median 7, range 1–13). DLTs in the first two cycles were grade 4 neutropenia and myocardial ischemia at the dose level paclitaxel/gemcitabine 150/2,000 mg/m², febrile neutropenia and grade 4 neutropenia at the dose level paclitaxel/gemcitabine 175/2,500 mg/m², fatal pneumonitis, sudden death and grade 3 neutropenia at the dose level paclitaxel/gemcitabine 175/3,000 mg/m². The MTD was paclitaxel 175 mg/m² and gemcitabine 2,500 mg/m². The average dose intensity at this dose level was 98%. The overall intent-to-treat response rate was 35.7% (95% confidence interval [CI] 17.97% - 53.47%). Overall median survival was 36 weeks (95% CI, 24-48). Conclusion: Paclitaxel and gemcitabine can be safely administered at a high dose intensity on an every-other-week schedule. The recommended phase II dose is paclitaxel 175 mg/m² and gemcitabine 2,500 mg/m².     

Clinical features of interstitial lung disease induced by standard chemotherapy (FOLFOX or FOLFIRI) for colorectal cancer

Background: Chemotherapy-induced interstitial lung disease (ILD) in colorectal cancer (CRC) patients is rarely reported, but its clinical features remain to be clarified.Patients and methods: Using a computerized database, we retrospectively identified patients who developed ILD from 734 patients with CRC treated with infusional 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX) or infusional 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) from April 2005 to December 2008 at the National Cancer Center Hospital East.Results: Of 734 patients, 11 patients developed ILD (1.5%) and 4 of those patients died (0.54%). Of the 11 patients, 10 showed pulmonary shadows other than lung metastases before chemotherapy. ILD developed during FOLFOX in six patients, at 137 days after completion of FOLFOX in one patient, during oxaliplatin interruption of FOLFOX in one patient and during FOLFIRI in the remaining three patients. FOLFOX had been administered at some point for all ILD patients, with a median of 10 cycles (range 2–17 cycles) and a median dose of administered oxaliplatin of 850 mg/m² (range 170–1445 mg/m²).Conclusions: ILD following FOLFOX or FOLFIRI is an uncommon but life-threatening complication. Care must be taken regarding the onset of ILD, not only during but also after chemotherapy for CRC.     

An EORTC phase I study of epirubicin in combination with fixed doses of cyclophosphamide and infusional 5-fu (CEF-infu) as primary treatment of large operable or locally advanced/inflammatory breast cancer

Purpose. The association of continuous infusion 5-fluorouracil, epirubicin (50mg/m² q 3weeks) and a platinum compound (cisplatin or carboplatin) was found to be very active in patients with either locally advanced/inflammatory (LA/I) [1, 2] or large operable (LO) breast cancer (BC) [3]. The same rate of activity in terms of response rate (RR) and response duration was observed in LA/I BC patients when cisplatin was replaced by cyclophosphamide [4]. The dose of epirubicin was either 50mg/m² [1, 2, 3] or 60mg/m²/cycle [4]. The main objective of this study was to determine the maximum tolerated dose (MTD) of epirubicin when given in combination with fixed doses of cyclophosphamide and infusional 5-fluorouracil (CEF-infu) as neoadjuvant therapy in patients with LO or LA/I BC for a maximum of 6 cycles. Patients and methods. Eligible patients had LO or LA/I BC, a performance status 0–1, adequate organ function and were 65 years old. Cyclophosphamide was administered at the dose of 400mg/m² day 1 & 8, q 4weeks and infusional 5-fluorouracil 200mg/m²/day was given day 1–28, q 4weeks. Epirubicin was escalated from 30 to 45 and to 60mg/m² day 1&8; dose escalation was permitted if 0/3 or 1/6 patients experienced dose limiting toxicity (DLT) during the first 2 cycles of therapy. DLT for epirubicin was defined as febrile neutropenia, grade 4 neutropenia lasting for 7 days, grade 4 thrombocytopenia, or any non-haematological toxicity of CTC grade 3, excluding alopecia and plantar-palmar erythrodysesthesia (this toxicity was attributable to infusional 5-fluorouracil and was not considered a DLT of epirubicin). Results. A total of 21 patients, median age 44 years (range 29–63) have been treated. 107 courses have been delivered, with a median number of 5 cycles per patient (range 4–6). DLTs on cycles 1 and 2 on level 1, 2, 3: grade 3 (G3) mucositis occurred in 1/10 patients treated at the third dose level. An interim analysis showed that G3 PPE occurred in 5/16 pts treated with the 28-day infusional 5-FU schedule at the 3 dose levels. The protocol was subsequently amended to limit the duration of infusional 5-fluorouracil infusion from 4 to 3 weeks. No G3 PPE was detected in 5 patients treated with this new schedule. Conclusions. This study establishes that epirubicin 60mg/m² day 1&8, cyclophosphamide 400mg/m² day 1&8 and infusional 5-fluorouracil 200mg/m²/day day 1-21, q 4 weeks is the recommended dose level. Given the encouraging activity of this regimen (15/21 clinical responses) we have replaced infusional 5-fluorouracil by oral capecitabine in a recently activated study.