Phase I/II study of S-1 combined with weekly docetaxel in patients with metastatic gastric carcinoma

We designed a phase I/II trial of S-1 combined with weekly docetaxel to determine the maximum tolerated dose (MTD) and recommended dose (RD) and to evaluate the efficacy and toxicity in metastatic gastric carcinoma (MGC). Patients with measurable disease received S-1 orally b.i.d. on days 1-14 and docetaxel intravenously on days 1 and 8 every 3 weeks. In phase I (n=30), each cohort received escalating doses of S-1 (30-45 mg m(-2) b.i.d.) and docetaxel (25-40 mg m(-2)); MTD was 45 mg m(-2) b.i.d. S-1/35 mg m(-2) docetaxel and RD was 40 mg m(-2) b.i.d. S-1/35 mg m(-2) docetaxel. Dose-limiting toxicities included grade 3 elevated liver enzymes, gastric perforation, grade 3 diarrhoea/fatigue, febrile neutropenia with grade 3 anorexia/fatigue, and neutropenic infection with grade 3 stomatitis/anorexia. In phase II (n=52), the overall response rate was 66.7% (95% confidence interval (CI): 53.8-79.6%) and the median time to progression and overall survival were 6.5 months (95% CI: 4.9-8.1) and 13.7 months (95% CI: 9.9-17.5), respectively. The most common grade 3/4 toxicity was neutropenia (29.4%), and febrile neutropenia/neutropenic infection occurred in 19.6% of patients. Non-haematological toxicities were generally mild. There was one treatment-related death due to pneumonitis. S-1 combined with weekly docetaxel is active in MGC with moderate toxicities.     

Phase I/II study of docetaxel and S-1 in patients with advanced gastric cancer

The aims of this phase I/II study of docetaxel and S-1 were to determine the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), and recommended dose (RD) in the phase I part and to explore the tumour response, survival and safety in the phase II part. Patients with histologically- or cytologically confirmed unresectable or recurrent gastric cancer were eligible. Treatment consisted of intravenous docetaxel on day 1 (starting dose 50 mg m(-2)) and oral S-1 at a fixed dose of 40 mg m(-2) twice daily on days 1-14, every 4 weeks up to six cycles. Nine patients took part in the phase I portion of the study. The MTD of docetaxel was determined to be 50 mg m(-2), with the DLTs of grade 3 infection associated with grade 3 neutropenia and grade 4 neutropenia during S-1 administration. The RD of docetaxel was 40 mg m(-2) in combination with S-1 40 mg m(-2) b.i.d. The efficacy and safety of this regimen was therefore assessed in 46 patients with at least one measurable lesion. The overall response rate and estimated median overall survival were 46% (95% CI, 31-61%) and 14.0 months (8.3-17.3 months), respectively. The most common grade 3/4 toxicity was neutropenia (67% of patients), which was predictable and manageable. This regimen showed promising activity with moderate toxicities in advanced gastric cancer.     

周剂量多西紫杉醇联合卡培他滨二线治疗晚期食管癌的临床观察

目的　观察周剂量多西紫杉醇联合卡培他滨二线治疗晚期食管癌的疗效和安全性。方法　２８例经顺铂加氟尿嘧啶方案一线化疗失败的晚期食管癌患者,应用多西紫杉醇２５ｍｇ／ｍ^２,静脉滴注１ｈ,ｄ_１、ｄ_８、ｄ_１５,卡培他滨（希罗达）１５００ｍｇ／ｍ^２,分每日２次口服,ｄ_１～ｄ_１４,２８天为１周期。结果　２８例患者中２６例可评价疗效,获ＣＲ１例,ＰＲ１０例,ＳＤ８例,ＰＤ７例,总有效率（ＣＲ＋ＰＲ）为３９.３％。所有患者中位疾病进展时间（ＴＴＰ）为４.２个月（９５％ＣＩ：１.６～６.０个月）,中位生存时间（ＯＳ）为７.８个月（９５％ＣＩ：６.３～９.３个月）。主要毒副反应为骨髓抑制,出现３～４级中性粒细胞减少１２例（４２.９％）,３级贫血５例（１７.９％）,３级血小板减少３例（１０.７％）,无治疗相关性死亡。结论　周剂量多西紫杉醇联合卡培他滨二线治疗晚期食管癌有一定疗效,患者耐受性较好,值得临床进一步研究。     

Efficacy and toxicity of gemcitabine plus docetaxel combination as a second line therapy for patients with advanced stage soft tissue sarcoma

Purpose: To assess the safety and efficacy of a gemcitabine plus docetaxel regimen as a second line therapy for patients with advanced soft tissue sarcoma (STS) resistant to doxorubicin and ifosfamide-based therapy. Patients and Methods: Medical records of 64 patients with advanced STS who received gemcitabine plus docetaxel regimen as a second line treatment between May 2006 and June 2011 were examined. All patients had been previously treated with doxorubicin plus ifosfamide-based regimen at first line setting. Patients received gemcitabine 900 mg/m2 on days one and eight intravenously over 90 minutes, followed by docetaxel 75 mg/m2 on day eight intravenously over one hour. Cycles were repeated every 3 weeks. Results: The male-to-female ratio was 37/27 and the median age was 44 years (range; 19-67 years). Objective responses were observed in 13 (20.3 %) patients (2 CR, 11 PR) and stable disease in 21 (32.8 %). Total clinical benefit (CR+PR+SD) was observed in 34 (53.1 %). Median overall survival (OS) was 18 months (95% confidence interval (CI):12.1-23.9) and Median time to progression (TTP) was 4.8 months (95% CI: 3.6-6). A total of 243 cycles of chemotherapy were administered. The median number of cycle was 3 (range;1-11). The most common grade 3-4 hematologic toxicity was neutropenia (35.9 %). The most common nonhematologic toxicities consisted of nausea/vomiting (37.5 %), mucositis (32.8 %), peripheral neuropathy (29.7%), and fatigue (26 %). There was no toxicity-related death. Conclusion: The combination of gemcitabine plus docetaxel is an active and tolerable regimen as a second line therapy for patients with advanced soft tissue sarcoma who have failed doxorubicin and ifosfamide-based therapy.     

Phase II study of docetaxel and cisplatin administered as three consecutive weekly infusions for advanced non-small cell lung cancer.

Weekly administration of low-dose taxane reduces myelosuppression and increases dose intensity as compared with an every third week schedule. We conducted a phase II trial of weekly docetaxel and cisplatin in patients with advanced non-small cell lung cancer (NSCLC) to evaluate safety and efficacy. Thirty-seven patients with chemona?ve stage IIIB (n=15), stage IV (n=16), or recurrence after operation (n=6) NSCLC received intravenous infusions of docetaxel at 35 mg/m(2) and cisplatin at 25 mg/m(2) for three consecutive weeks, followed by a week of rest. There were ten partial responses for an objective response rate of 30% (95% confidence interval (CI), 15-46%) in 33 evaluable patients and 27% (95% CI, 13-41%) in the intent-to-treatment population. The median survival was 12.8 months (range 2.5-17.1), and the 1-year survival was 54%. Hematologic toxicities, which were mild, included grade 4 neutropenia in 6%. There were none with febrile neutropenia or severe (grade 3-4) infections, and no septic deaths. The common nonhematologic toxicities included grade 2-3 nausea and vomiting (44%) and grade 2-3 diarrhea (14%). Consecutive weekly administrations of docetaxel and cisplatin for 3 weeks produces minimal myelosuppression and shows activity in the treatment of chemona?ve patients with advanced NSCLC. A randomized phase III trial is warranted to compare this 3 consecutive weeks protocol with administration of docetaxel and cisplatin every third week.     

Phase II multicentre study of docetaxel plus 5-fluorouracil in patients with anthracycline-pretreated metastatic breast cancer

The purpose of the study was to determine the efficacy and safety of docetaxel plus continuous infusion of 5-fluorouracil (5-FU) in patients with metastatic breast cancer previously treated with anthracyclines. A total of 41 patients with histologically proven metastatic breast cancer and performance status 0-2, who had received at least one anthracycline-containing regimen, received docetaxel 85 mg m(-2) followed by continuous infusion of 5-FU 750 mg m(-2) day(-1) for 5 days every 3 weeks for up to eight cycles. All patients received corticosteroid premedication, but there was no prophylactic colony-stimulating factor support. The most frequent metastatic sites were the liver (61%), bone (29%), and lung (29%). All 41 patients were assessable for toxicity and 30 were eligible and assessable for efficacy. The objective response rate was 70.0% (95% CI: 53.6-86.4%) for the per protocol group and 53.7% (95% CI: 38.4-68.9%) for the intent-to-treat (ITT) population. For the ITT population, median duration of response was 8.4 months (95% CI: 6.7-12.2 months), median time to progression was 6.7 months (95% CI 5.5-8.6 months), and median survival was 17 months (95% CI: 12.3-not recorded months). Grade 3/4 neutropenia occurred in 54% of patients, with febrile neutropenia in 24% of patients and 5% of cycles, but infections were rare. Stomatitis was frequent, grade 3 in 24% of patients and grade 4 in one patient (2%), but manageable. Diarrhoea was rare, grade 3 in 7% of patients and 1% of cycles. Other grade 3/4 nonhaematological toxicities were infrequent. In conclusion, this docetaxel/5-FU regimen is highly active and well tolerated in patients with anthracycline-pretreated metastatic breast cancer. The efficacy is particularly promising, as one-third of patients were either second-line and/or anthracycline-resistant/refractory.     

Gemcitabine combined with epirubicin in the treatment of patients with locally advanced or metastatic breast cancer: a phase II study

This phase II study of gemcitabine and epirubicin evaluated the activity and toxicity in advanced breast cancer. Female patients with stage IIIB or IV breast cancer received gemcitabine 1000 mg/m2 and then epirubicin 15 mg/m2 on days 1, 8, and 15 of 28-day cycles. Thirty-five patients with stage IV disease, a median age of 59 years (range, 39-73), and a median Karnofsky performance status of 90 (range, 60-100) were enrolled. Fourteen (40.0%) patients received prior chemotherapy (12 adjuvant, 4 metastatic, 2 both). Of 35 evaluable patients, 10 had PR, for an overall RR of 28.6%, and 12 (34.3%) patients had SD. Median time to progression and overall survival were 5.8 months (95% CI, 3.4-9.5 months) and 17.1 months (95% CI, 11.2-19.9 months), respectively. WHO grade 3/4 neutropenia occurred in 51.5% of patients without febrile neutropenia, and grade 3 thrombocytopenia in 29.4% of patients without hemorrhage or platelet transfusions. The most common nonhematologic toxicities were grade 3 alopecia (38.2%) and nausea/vomiting (11.4%). There were no grade 4 nonhematologic toxicities. Gemcitabine plus epirubicin is active and well tolerated in patients with metastatic breast cancer. Future studies should continue to evaluate the impact of various schedules on outcome.     

Phase II study of combination therapy with S-1 and irinotecan for advanced non-small cell lung cancer: west Japan thoracic oncology group 3505

PURPOSE: To evaluate the efficacy and toxicity of combination therapy with the oral fluoropyrimidine formulation S-1 and irinotecan for patients with advanced NSCLC. EXPERIMENTAL DESIGN: Chemotherapy-naive patients with advanced NSCLC were treated with i.v. irinotecan (150 mg/m2) on day 1 and with oral S-1 (80 mg/m2) on days 1 to 14 every 3 weeks. RESULTS: Fifty-six patients (median age, 63 years; range, 40-74 years) received a total of 286 treatment cycles (median, 5; range, 1-15). No complete responses and 16 partial responses were observed, giving an overall response rate of 28.6% [95% confidence interval (95% CI), 17.3-42.2%]. Twenty-four patients (42.9%) had stable disease and 12 patients (21.4%) had progressive disease as the best response. The overall disease control rate (complete response + partial response + stable disease) was thus 71.4% (95% CI, 57.8-82.7%). Median progression-free survival was 4.9 months (95% CI, 4.0-6.4 months), whereas median overall survival was 15 months. Hematologic toxicities of grade 3 or 4 included neutropenia (25%), thrombocytopenia (3.6%), and anemia (3.6%), with febrile neutropenia being observed in four patients (7.1%). The most common nonhematologic toxicities of grade 3 or 4 included anorexia (14.3%), fatigue (8.9%), and diarrhea (8.9%). There were no deaths attributed to treatment. CONCLUSIONS: The combination of S-1 and irinotecan is a potential alternative option with a favorable toxicity profile for the treatment of advanced NSCLC. This nonplatinum regimen warrants further evaluation in randomized trials.     

Phase II study of docetaxel and irinotecan combination chemotherapy in metastatic gastric carcinoma

The current treatment for metastatic gastric cancer (MGC) consists of cisplatin and/or fluorouracil (5-FU) based combination chemotherapy, but cisplatin-based regimens are associated with considerable toxicity. We evaluated the efficacy and safety of a noncisplatin-, non-5-FU-containing regimen, docetaxel/irinotecan in MGC. Chemo-naive patients with MGC received docetaxel (30 mg m(-2)) and irinotecan (70 mg m(-2)) on days 1 and 8 every 3 weeks. The 48 eligible patients (median age 56 years) received a median of four cycles of docetaxel/irinotecan (range 1-18). Of the 46 patients in whom efficacy could be evaluated, 21 showed a partial response (response rate=45.7%; 95% confidence interval (CI) 31.3-60.1%). At a median follow-up of 15.0 months, the median time to progression was 4.5 months (95% CI 3.8-5.2 months) and overall survival was 8.2 months (95% CI, 5.8-10.6 months). Grade 3/4 neutropenia developed in 57.4% of patients, and febrile neutropenia/neutropenic infection in 19.1%. Nonhaematological toxicities were moderate; grade 3/4 diarrhoea occurred in 19.1% of patients, however, was manageable by a dose reduction. There was one possible treatment-related death. In conclusion, weekly docetaxel/irinotecan is a promising outpatient regimen in MGC, with appropriate dose modification.     

A phase I-II study of docetaxel and atrasentan in men with castration-resistant metastatic prostate cancer

PURPOSE: The primary aims of this phase I-II study were to determine the maximum tolerated dose, dose-limiting toxicity, pharmacokinetics, and preliminary efficacy of the combination of docetaxel and the endothelin A receptor antagonist atrasentan as first-line treatment for men with metastatic castration-resistant prostate cancer. EXPERIMENTAL DESIGN: Patients were treated with docetaxel at doses ranging from 60 to 75 mg/m(2) every 21 days, with daily oral atrasentan 10 mg starting on day 3. Patients were treated until evidence of disease progression or unacceptable toxicity. RESULTS: Thirty-one patients were enrolled over three docetaxel dose levels (8 at 60 mg/m(2), 19 at 70 mg/m(2), and 4 at 75 mg/m(2)) including dose expansion at 70 mg/m(2). The maximum tolerated dose of docetaxel was 70 to 75 mg/m(2). Drug-related grade 3-4 toxicities included neutropenia (50-63%) and febrile neutropenia (16-25%); other grade 1-2 toxicities included fatigue, peripheral edema, diarrhea, headache, rhinitis, anorexia, and nausea. Confirmed prostate-specific antigen (PSA) responses were observed in 23% [95% confidence interval (95% CI), 10-41%]; the rate of >30% declines in PSA was 35% (95% CI, 19-55%). Median overall survival was 17.6 months (95% CI, 13.0-23.2) and median progression-free survival was 4.2 months (95% CI, 2.3-5.8). Significant declines in bone alkaline phosphatase and serum N-telopeptides were observed with therapy. CONCLUSIONS: The maximum tolerated dose of every-3-week docetaxel with 10 mg atrasentan is 70 to 75 mg/m(2). Overall survival and progression-free survival are comparable to that seen with docetaxel and prednisone, whereas the rates of PSA decline are slightly lower than expected. A phase III study of this combination with prednisone has been initiated and is ongoing.     

Docetaxel and capecitabine in patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction: a phase II study from the North Central Cancer Treatment Group.

BACKGROUND: Previous studies suggest that the combination of docetaxel and capecitabine are worthy of further testing in patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction. We therefore undertook this phase II study to test this combination in a multi-institutional, first-line clinical trial. PATIENTS AND METHODS: Forty-four eligible patients with histologic or cytologic confirmation of the above malignancy were recruited. The cohort had Eastern Cooperative Oncology Group performance scores of 0, 1 and 2 in 59%, 39% and 2% of patients, respectively. Median age was 57 years (range 32-77 years). Adequate organ function was a requirement for study entry. All patients were prescribed docetaxel 75 mg/m2 intravenously on day 1 and capecitabine 825 mg/m2 orally twice a day on days 1-14 of a 21-day cycle. RESULTS: The tumor response rate was 39% [95% confidence interval (CI) 23% to 55%]. There were two complete responses and the rest were partial. Median survival was 9.4 months (95% CI 6.3-10.7 months) and median time-to-tumor progression was 4.2 months (95% CI 3.6-5.6 months). There was one treatment-related death from a myocardial infarction and dysrhythmia. Commonly occurring grade 3 adverse events included neutropenia (11 patients), infection (five patients), constipation (three patients), thrombosis (three patients), dyspnea (three patients) and hand-foot syndrome (three patients). In addition, 24/45 patients developed grade 4 neutropenia. CONCLUSIONS: The regimen docetaxel and capecitabine shows activity in patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction. This regimen merits further study.     

Phase II trial of bevacizumab in combination with weekly docetaxel in metastatic breast cancer patients.

PURPOSE: To evaluate the safety and efficacy of bevacizumab and weekly docetaxel as first- or second-line therapy in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Twenty-seven MBC patients received i.v. bevacizumab at 10 mg/kg on days 1 and 15 in combination with i.v. docetaxel 35 mg/m2 on days 1, 8, and 15 of a 28-day cycle. Primary end points were to assess toxicity, overall response rate, and progression-free survival. A secondary end point was to assess the relationship between plasma endothelial and cell adhesion markers and clinical outcomes. RESULTS: One-hundred fifty-eight treatment cycles were administered with a median of six cycles (range 1-15 cycles) per patient. The most common grade 4 toxicities per patient were as follows: 2 (7%)-pulmonary embolus, 1 (4%)-febrile neutropenia, and 1 (4%)-infection; grade 3 toxicities were 4 (15%)-neutropenia, 4 (15%)-fatigue, 2 (7%)-neuropathy, 2 (7%)-athralgias, 2 (7%)-stomatitis, 1 (7%)-pleural effusion, and 1 (4%)-hypertension. The overall response rate was 52% [95% confidence interval (95% CI), 32-71%], median response duration was 6.0 months (95% CI, 4.6-6.5 months), and the median progression-free survival was 7.5 months (95% CI, 6.2-8.3 months). In hypothesis-generating univariate and limited multivariate analyses, E-selectin was statistically significantly associated with response to the combination. CONCLUSION: Bevazicumab in combination with weekly docetaxel is active with acceptable toxicities in MBC. Additional studies evaluating E-selectin as a marker of response to bevacizumab-containing chemotherapy are warranted.     

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     

A phase II study of oxaliplatin with low dose leucovorin and bolus and continuous infusion 5-fluorouracil (modified FOLFOX-4) as first line therapy for patients with advanced gastric cancer

To determine the activity and toxicities of a low dose leucovorin (ldLV) plus fluorouracil (5-FU) regimen, combined with oxaliplatin administered fortnightly (modified FOLFOX-4), as a first-line therapy for patients with advanced gastric cancer. Patients were treated with cycles of oxaliplatin 85 mg/m² on day 1 plus LV 20 mg/m², followed by 5-FU a 400 mg/m² bolus and a 22 hour continuous infusion of 600 mg/m² 5-FU on days 1 - 2 every two week intervals. Forty-five patients were enrolled in this study. Forty-two patients were assessable for response. One of the 42 patients demonstrated complete response, and 20 partial responses, and overall response rate of 50%. The median time to progression and overall survival time were 7.7 months (95% CI: 3.6 - 11.9 months) and 11.2 months (95% CI: 9.1 - 13.3 months), respectively. Major hematologic toxicities included grade 1 - 2 anemia (39.7%), neutropenia (30.4%) and grade 3 - 4 neutropenia (10.9%). Twelve cycles were associated with neutropenic fever. The most common non-hematological toxicities were grade 2 nausea/vomiting (20%). There was no treatment related death. The modified FOLFOX-4 regimen was found to be a safe and effective first line therapy in advanced gastric cancer.     

A weekly 24-h infusion of high-dose 5-fluorouracil (5-FU)+leucovorin and bi-weekly cisplatin (CDDP) was active and well tolerated in patients with non-colon digestive carcinomas

In patients with non-colon digestive carcinomas, various schedules and doses of 5-fluorouracil (5-FU) and leucovorin combined with cisplatin (CDDP) have been used extensively. The present study explored the toxicity and activity of a weekly 24-h infusion of high dose 5-FU modulated by high dose leucovorin with bi-weekly CDDP. 59 patients with measurable disease were treated with a weekly infusion of high dose 5-FU (2 or 2.6 g/m2)+leucovorin 500 mg/m2 for 6 weeks and a bi-weekly dose of CDDP (50 mg/m2). All patients had metastatic or locoregionally advanced disease and had a performance status < or =3. All patients were evaluable for toxicity and 58 for response. Toxicity was different according to the schedule of 5-FU. Serious adverse events occurred most frequently when 5-FU was given at a dose of 2.6 g/m2 with a high incidence of grade 3/4 neutropenia (16%) and febrile neutropenia (13%), and led to dose reductions in both CDDP and 5-FU in 13 patients (34%). For patients who started 5-FU at a dose of 2 g/m2, no reduction in 5-FU was required, and only 4 patients required a dose reduction of CDDP (19%). Grade 3/4 neutropenia was seen in 10% of patients of this group and only 1 patient required hospitalisation for febrile neutropenia. Other grade 3/4 toxicities were rare in both groups. Renal toxicity was infrequent and mild and did not require dose adjustments. The overall response rate was 33%; 19 patients achieved a partial responses (PR). No patient had a complete response (CR). The median duration of response was 5.7 months (range 2-24 months) and the median survival was 7.9 months ( range: 1-30, 95% confidence interval (CI): 7-9). The combination of weekly 24-h infusion of high dose 5-FU with leucovorin and bi-weekly cisplatin seems a well-tolerated and active treatment in non-colon digestive carcinomas. A dose of 2 g/m2 of 5-FU seems to be recommended.     

Combination chemotherapy with paclitaxel, cisplatin and fluorouracil for patients with advanced and metastatic gastric or esophagogastric junction adenocarcinoma: a multicenter prospective study

Objective:To evaluate the efficacy and toxicity of the combination regimen of paclitaxel,cisplatin and 5-FU(PCF) as first-line or second-line therapy in patients with advanced gastric and esophagogastric junction(EGJ) adenocarcinoma in China.Methods:The patients were treated with paclitaxel 150mg/m2 on d1;fractionated cisplatin 15mg/m 2 and continuous infusion 5-FU 600mg/(m2·d) intravenously on d1-d5 of a 21-d cycle until disease progression or unacceptable toxicities.Results:Seventy-five patients have been enrolled,among which,41 received PCF regimen as the first-line therapy(group A) and 34 received the regimen as the second-line therapy(group B) with the median age of 59 years old and Karnofsky performance status(KPS) score ≥80.Toxicities were analyzed in all 75 patients.Seventy-one patients were evaluable for efficacy.The median overall survival(mOS) was 12.0 months(95% CI:7.9-16.2 months) in group A and 7.3 months(95% CI:4.3-10.3 months) in group B,respectively.The median progression-free survival(mPFS) was 5.7 months(95% CI:4.1-7.2 months) and 5.0 months(95% CI:3.1-6.9 months),respectively.The response rate(CR+PR) was 40%(16/40;95% CI:24.9-56.7%) in group A and 22.6%(7/31;95% CI:9.6-41.1%) in group B.Major grade 3 or 4 adverse events include neutropenia(41.3%),febrile neutropenia(9.3%),nausea/anorexia(10.7%),and vomiting(5.3%).There was no treatment-related death.Conclusions:The combination chemotherapy with PCF is active and tolerable as first-line and secondline therapy in Chinese patients with advanced gastric and EGJ adenocarcinoma.The response and survival of PCF are same as those of DCF,but the tolerance is much better.     

Biweekly docetaxel and vinorelbine in anthracycline-resistant metastatic breast cancer: a multicenter phase II study

The aim of this study was to determine the efficacy and toxicity of a biweekly combination of docetaxel and vinorelbine in patients with metastatic breast cancer (MBC) previously treated with anthracyclines. Eligible patients (n = 49) with MBC received vinorelbine, 25 mg/m2, followed by docetaxel, 60 mg/m2. Cycles were repeated every 14 days for a total of 8 planned cycles. Response rate was evaluated every 4 cycles. All 49 patients were evaluable for safety and 44 for efficacy. Vinorelbine plus docetaxel resulted in an overall response rate of 45% (CI 95%: 31-60) with 2 (4%) complete responses and 18 (41%) partial responses. Patients with visceral metastasis achieved a lower response rate than those without (33% versus 60%, p = 0.044). Time to progression was 11.0 months (CI 95%: 8.6-13.5), and median overall survival was 12.7 months (CI 95%: 9.0-16.4). The most common grade III to IV hematologic adverse events was neutropenia (65% of patients). Febrile neutropenia was observed in 9 cycles (3%) and in 7 patients (14%). Grade III to IV nonhematologic toxicity was rare. Biweekly combination of docetaxel and vinorelbine is an effective and well-tolerated regimen in anthracycline-resistant MBC.     

Combination second-line chemotherapy with gemcitabine and docetaxel for recurrent non-small-cell lung cancer after platinum-containing chemotherapy: a phase I/II trial

PURPOSE: In a randomized trial, docetaxel monotherapy yielded longer survival than the best supportive care in patients with non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy, and combination chemotherapy regimens containing docetaxel have been assessed to enhance the efficacy of second-line chemotherapy. We conducted a phase I/II trial of gemcitabine and docetaxel in patients with recurrent NSCLC after platinum-based chemotherapy and with an ECOG performance status (PS) of 0 or 1. PATIENTS AND METHODS: Docetaxel administration was fixed at a dosage of 60 mg/m(2) on day 8, and gemcitabine was administered on days 1 and 8. The starting dose level of gemcitabine was 800 mg/m(2) (level 0), and the subsequent dose level of gemcitabine was 1000 mg/m(2) (level +1). Treatment was repeated every 3 weeks. RESULTS: In the phase I study, 13 patients were enrolled, and in the phase II study, 29 patients were enrolled. Neutropenic fever and omission of treatment on day 8 due to leukopenia (leukocyte count less than 3000/mm(3)) were dose-limiting toxicities (DLTs). Three of six patients experienced DLTs at level +1, which was the maximum tolerated dose. Gemcitabine 800 mg/m(2) on days 1 and 8 plus docetaxel 60 mg/m(2) on day 8 (level 0) was recommended for the phase II study. An objective response was observed in 8 (28%) of the 29 patients. The median time to disease progression was 4.2 months (95% CI 0.9-7.7 months). The median survival time was 11.1 months (95% CI 9.9-12.4 months), and the 1-year survival rate was 41%. The most common toxicity, though mild, was hematologic, and consisted of grade 4 neutropenia (18%), grade 3 febrile neutropenia (11%), and grade 3 thrombocytopenia (11%). There were no toxic deaths. Grade 3 non-hematologic toxicities included nausea (4%) and rash (4%). CONCLUSIONS: The combination chemotherapy of gemcitabine and docetaxel is active and well tolerated in patients with recurrent NSCLC after platinum-based chemotherapy and with a good PS.     

Application of prolonged microdialysis sampling in carboplatin-treated cancer patients

Purpose  To determine the dose-limiting toxicity (DLT) and activity of combination with docetaxel and S-1 on unresectable gastric cancer. Patients and methods  Docetaxel was administered intravenously on day 1 and S-1 was administered orally on days 1–14, every 3 weeks. Doses of each drug in phase I study were docetaxel 60–75 mg/m² and S-1 60–80 mg/m². A phase II study was conducted with the recommended dose (RD) based on phase I. Results  Sixty-five patients (median age 54 years) were enrolled. The DLTs were neutropenia with fever or stomatitis. The RD was docetaxel 75 mg/m² and S-1 60 mg/m². Two patients (aged 66 and 64 years) developed septic shock during the initial part of phase II study. A phase I study at lower dose (docetaxel 60 mg/m² and S-1 80 mg/m²) was conducted for patients older than 60 years, and this dose was determined as the RD for these patients. In the phase II study, frequent grade 3/4 toxicities were neutropenia (47%) and febrile neutropenia (26%). The overall response rate was 50% (95% CI, 35–66%) and median survival was 15.3 months (95% CI, 10.0–20.6 months). Conclusions  Combination with docetaxel and S-1 was active against advanced gastric cancer and gave manageable toxicities. Supported in part by a grant from the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (0412_CR01_0704_0001).     

A phase II study of weekly docetaxel plus capecitabine for patients with advanced nonsmall cell lung carcinoma

BACKGROUND: Docetaxel is an active agent in advanced nonsmall-cell lung carcinoma (NSCLC) and demonstrates preclinical and clinical synergism with capecitabine. We conducted the current Phase II study to evaluate the efficacy and safety of the docetaxel/capecitabine combination in chemotherapy-naive patients with advanced NSCLC. METHODS: Eligibility required Stage IIIB or IV NSCLC, bidimensionally measurable disease, and an Eastern Cooperative Oncology Group performance score of 2 or lower. Treatment consisted of docetaxel 36 mg/m(2) intravenously on Days 1 and 8 plus capecitabine 1000 mg/m(2) orally twice per day on Days 1-14 of a 21-day cycle, for a maximum of 6 cycles. RESULTS: Of 39 patients enrolled, 39 and 36 patients were evaluated for toxicity and response, respectively. The overall response rate was 53% (95% confidence interval [CI], 37-69%) with 19 partial responses (no complete response). The median duration of response was 6.2 months (range, 2.1-15.7 months). At a median follow-up of 14.2 months, 19 patients died. The median overall survival time was 17.8 months, with a 1-year survival rate of 56.4% (95% CI, 40.9-72.0%). There were two treatment-related deaths (one death due to pneumonia and one due to sepsis). Hematologic toxicity was mild to moderate. Thirteen percent of the patients had Grade 3 or 4 neutropenia. However, Grade 2 or 3 nonhematologic toxicities were frequent, which included asthenia (51%), stomatitis (33%), hand-foot syndrome (33%), and diarrhea (29%). CONCLUSIONS: The docetaxel/capecitabine combination showed promising antitumor activity for chemotherapy-naive patients with advanced NSCLC, However, it was frequently associated with moderate-to-severe nonhematologic toxicities, suggesting clinical synergism in both efficacy and toxicity. Further adjustment of the dose schedule is recommended to maximize the therapeutic index.