Sequential methotrexate and 5-fluorouracil therapy for gastric cancer patients with peritoneal dissemination: a retrospective study

Background. Most gastric cancer patients with peritoneal dissemination have been excluded from clinical studies because they usually have no measurable lesions. They also have a high risk of toxicity because of complications such as intestinal obstruction and ascites. We conducted a retrospective analysis to evaluate the efficacy and feasibility of sequential methotrexate (MTX) and 5-flurorouracil (5FU) therapy for this population. Methods. This analysis was based on 56 consecutive chemotherapy-naive patients with confirmed peritoneal dissemination of gastric cancer who were being treated with sequential MTX/5FU. The therapy comprised a weekly schedule of MTX 100 mg/m², given as a bolus infusion 3 h prior to a bolus infusion of 5FU 600 mg/m². Leucovorin 10 mg/m² was administered six times, every 6 h, starting 24 h after MTX administration. Results. Evidence of peritoneal dissemination was confirmed by laparotomy in 16 patients, by cytologic examination of ascites in 11 patients, and by clinical imaging in 29 patients (15 with ascites, 13 with intestinal obstruction; in 10 of the 29 patients, detection was by barium enema or computed tomography [CT] scan). Neutropenia of grade 3 or worse and anemia were observed in 8 (14%) and 10 (18%) of the 56 patients, respectively. There was one treatment-related death due to neutropenic sepsis. Of the 26 patients with measurable lesions, 9 showed a response (36%). The median survival time and median time to treatment failure were 259 days and 167 days, respectively. Objective improvement of ascites was seen in 13 of 26 patients (50%), including 5 with showed complete disappearance of ascites. Seven of the 15 patients (47%) with intestinal obstruction showed resolution, and 8 of the 21 patients (38%) who needed nutritional support before the treatment were free of that support for a median duration of 220 days after the completion of the treatment. Forty-seven of the 56 patients (84%) could be treated at outpatient clinics. Conclusions. This regimen may be of clinical benefit for patients with peritoneal dissemination of gastric cancer. Received: August 24, 2001 / Accepted: October 19, 2001     

A phase II study of sequential methotrexate and 5-fluorouracil in colorectal carcinoma

Nineteen patients with locally recurrent or metastatic colorectal carcinomas were treated with 3-weekly cycles of methotrexate (MTX) given as a loading dose of 100 mg m⁻² and a subsequent 12 h infusion of 400 mg m⁻², followed by 5-fluorouracil (5-FU) 900 mg m⁻² as a bolus injection on completion of infusion. No objective responses were seen in 14 evaluable patients. One early death was treatment related, and four patients were withdrawn from the study after a single course as toxicity was considered unacceptable. The results suggest that in this regimen of sequential MTX and 5-FU, any synergism may be restricted to drug toxicity as no therapeutic benefit was evident.     

胃癌骨转移患者临床病理与预后分析

目的 本文旨在探讨胃癌骨转移患者的临床病理特征,筛选预后因子。方法 回顾性分析2007年4月—2013年12月哈尔滨医科大学附属肿瘤医院的157例胃癌骨转移患者临床资料。结果 157例胃癌骨转移患者中,确诊胃癌至骨转移的中位时间为280.5天。多发骨转移124例,单发骨转移22例。最常见的骨转移部位是脊柱(88.5%)、骨盆(51.6%)和肋骨(51.0%)。多数患者伴有骨外脏器转移(78.3%)。骨转移的胃癌患者病理分化大多较差,以低分化腺癌(69.3%)及印戒细胞癌及粘液腺癌(33.1%)多见。胃癌患者发生骨转移后的中位生存时间为109天。单因素分析显示CEA水平、LDH水平、血红蛋白浓度、白蛋白浓度、伴有骨外转移、化疗及双膦酸盐治疗与胃癌骨转移患者预后有关(P＜0.05)。多因素分析显示CEA水平、伴有骨外转移、化疗和双膦酸盐治疗均是胃癌骨转移预后的独立因素。结论 CEA升高及伴有骨外转移是其独立的不良预后因素,化疗和双膦酸盐药物治疗可能改善患者的预后。     

Extensive liver metastasis of gastric cancer effectively treated by hepatic arterial infusion of 5-fluorouracil/cisplatin

Most gastric cancer patients with jaundice caused by extensive liver metastasis show no tumor shrinkage response to systemic chemotherapy, while often showing severe adverse reactions. Their prognosis is very poor. We experienced two patients for whom hepatic arterial infusion (HAI) of 5-fluorouracil (5-FU) and cisplatin through an implantable port was effective for treating extensive liver metastasis. One patient had jaundice (serum bilirubin level before HAI therapy, 12.4 mg/dl) caused by metachronous liver metastasis, and prior systemic chemotherapy with 5-FU and irinotecan had not been effective. The other patient had gastric cancer with synchronous liver metastasis and also exhibited jaundice (serum bilirubin level before HAI therapy, 11.8 mg/dl). Both patients were treated with HAI of cisplatin, 20 mg/m ² for 30 min on day 1, and continuous intraarterial infusion of 5-FU, 300 mg/m ² , from day 1 to day 4 every week. Their metastatic liver tumors were significantly reduced in volume and the jaundice disappeared. They survived for 30 and 27 weeks, respectively. A pharmacokinetic study conducted during the period of partial remission revealed that the extraction ratios of 5-FU and cisplatin in the liver were 0.89 and 0.024, respectively, suggesting a favorable first-pass effect of 5-FU. Although our findings here suggest that the successful local control of liver metastasis could improve the deteriorated condition and prolong the survival in some patients with far advanced cancer, it is essential to pay much attention to possible adverse effects during the treatment. Received: April 17, 2000 / Accepted: July 12, 2000     

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.     

Lacrimal duct stenosis and other ocular toxicity associated with adjuvant cyclophosphamide, methotrexate and 5-fluorouracil combination chemotherapy for early stage breast cancer

Certain side-effects of chemotherapy are well recognized but ocular toxicity is often underestimated. This retrospective study was undertaken after we became aware of a case of irreversible lacrimal duct stenosis in a woman receiving adjuvant chemotherapy for early stage breast cancer. Using the chemotherapy records, 128 patients who received adjuvant cyclophosphamide, methotrexate and 5-fluorouracil combination chemotherapy for early stage breast cancer over a 2 1/2-year period were identified. The case notes of these patients were reviewed and an 18% incidence of ocular side-effects, including four other cases of epiphora, was identified. The epiphora resolved fully on completion of chemotherapy in these four patients but not in the index patient. The optimal management of these side-effects is unclear but it needs to be tailored to the particular toxicity experienced by the patient.     

In-vitro effect of a combination of 5-fluorouracil (5-FU) and cisplatin (CDDP) on human gastric cancer cell lines: timing of cisplatin treatment

Abstract. Background: To date, we have few effective chemotherapeutic agents against advanced and recurrent gastric cancer. 5-Fluorouracil (5-FU) and cisplatin (CDDP) are the most widely used drugs, and their combination has demonstrated favorable outcomes. However, the method (especially the timing) of CDDP administration is not well established. Methods: We examined the in-vitro effect of a combination of 5-FU and CDDP on four human gastric cancer cell lines: MKN-1, MKN-28, MKN-45, and MKN-74. The cell lines were exposed to 50% of the inhibitory concentrations of 5-FU and CDDP for 72 h and 8 h, respectively. CDDP was applied before, simultaneously with, and after the start of treatment with 5-FU. Results: When CDDP was applied after 5-FU, the cytotoxic activity against MKN-28, MKN-45, and MKN-74 was significantly potentiated. Against MKN-1, the earlier the initiation of CDDP treatment, the stronger was the cytotoxic effect. Conclusion: Our results suggest that the cytotoxicity of a combination of 5-FU and CDDP against human gastric cancer cells is both cell-line- and schedule-dependent and is especially affected by the timing of the CDDP treatment. Received: August 22, 2001 / Accepted: December 7, 2001     

Gastric phenotype signet-ring cell carcinoma of the stomach with multiple bone metastases effectively treated with sequential methotrexate and 5-fluorouracil

A 63-year-old woman presented with an abnormal serum alkaline phosphatase (ALP) level. Computed tomography (CT) scan of the abdomen and pelvis and radioisotope (RI) examination led to a strong suspicion of systemic bone metastatic tumors, although the origin was not known. Biopsies from bone metastatic lesions in the left ilium were performed under CT scan, and signet-ring cell carcinoma cells were detected pathologically. Also, a 0-IIc-like lesion was observed endoscopically in the stomach, and signet-ring cell carcinoma cells were also detected histologically. The patient's platelet (Plt) levels were reduced and slight bleeding from the gingiva was detected when she brushed her teeth. Both the stomach and the bone metastatic lesions exhibited a gastric phenotype (G type) phenotypically. From these findings, we diagnosed the patient as having advanced (inoperable) stomach cancer with multiple bone metastases; she also exhibited disseminated intravascular coagulation (DIC). We treated her with sequential methotrexate and 5-fluorouracil (sequential MTX/5-FU) therapy after obtaining her informed consent. After six cycles of the chemotherapy, the abnormal ALP and Plt levels were alleviated. At present, she is receiving weekly sequential MTX/5-FU therapy at the outpatient oncology unit; she has been receiving the therapy for about 7 months since the detection of the bone metastases and has had a total of 17 cycles. In conclusion, sequential MTX/5-FU therapy was effective for a patient with G-type signet-ring cell carcinoma of the stomach with bone metastases, suggesting that the phenotypic classification may be one of the useful markers for prediction of the effectiveness of chemotherapy in patients with inoperable advanced stomach cancer.     

Gemcitabine (GEM) plus oxaliplatin, folinic acid, and 5-fluorouracil (FOLFOX-4) in patients with advanced gastric cancer

Background and aims: oxaliplatin in combination with folinic acid (FA) and infusional 5-fluorouracil (5-FU) has shown significant anti-tumor activity in gastric cancer patients (FOLFOX). Previous studies have shown that gemcitabine (GEM), a new fluorinated anti-metabolite, enhances the individual anti-tumor activity of either 5-FU or oxaliplatin. We have therefore designed a multi-center phase II trial in order to test a novel GEM + FOLFOX-4 regimen in patients with metastatic gastric cancer. Methods: we enrolled 36 patients, 28 males and 8 females, with an average age of 64.4 years (range 37–78), who received bi-weekly treatment with GEM (1,000 mg/m² on day 1), levo-FA (100 mg/m² on days 1 and 2), a 5-FU (400 mg/m²) bolus injection followed by 22-h continuous infusion (800 mg/m²) on days 1 and 2, and oxaliplatin 85 mg/m² in a 4–6 h intravenous (i.v.) infusion before the second FUFA administration on day 2. Results: the most frequent side effect was grade 1–2 hematological toxicity and late sensorial neurotoxicity. Two patients developed hypersensitivity to oxaliplatin while another developed an aseptic eosinophilic pneumonitis. Two patients refused to continue the treatment after two cycles of chemotherapy and were lost at the follow-up. Among the remaining 34 patients four achieved a complete response, 15 a partial response, 12 had a stable disease and three progressed. Conclusions: these results may grant the rationale to evaluate this multi-drug combination in randomized phase III trials in advanced gastric cancer.     

Phase I dose-escalating study of 24-h continuous infusion of 5-fluorouracil in combination with weekly docetaxel and cisplatin in patients with advanced gastric cancer

Purpose

To determine the maximum-tolerated dose (MTD) of a 24-h continuous infusion of 5-fluorouracil (5-FU) when administered in combination with a fixed weekly dose of docetaxel and cisplatin in patients with advanced gastric cancer.

Methods

Patients with advanced gastric adenocarcinoma (n = 21) received a weekly regimen of docetaxel, cisplatin and 5-FU (DCF) for 3 consecutive weeks every 4 weeks. The doses of docetaxel and cisplatin were fixed at 33.3 and 30 mg/m², respectively. The dose of 5-FU was increased from a starting dose of 1,000 mg/m² to the MTD.

Results

A total of 53 cycles of chemotherapy were administered (median = 3 cycles/patient). The MTD of 5-FU was 1,750 mg/m². All 21 patients were assessed for toxicity and 19 patients (90%) were evaluated for response. Both grade 3–4 hematologic and non-hematologic toxicities occurred in less than 10% of patients and there were no treatment-related deaths. Among the 19 patients, we observed 1 complete and 4 partial responses for an overall response rate of 26% (95% CI: 6–46%). This rate increased to 39% (95% CI: 12–66%) in 13 chemotherapy-naïve patients.

Conclusions

A consecutive weekly DCF regimen at 4-week intervals appears feasible for advanced gastric cancer with a favorable toxicity profile. The recommended doses are 33.3 mg/m² of docetaxel, 30 mg/m² of cisplatin and 1,500 mg/m² of a 24-h continuous intravenous infusion of 5-FU. The response of this weekly regimen in our study was favorable and deserved further investigation in a phase II trial.     

氟尿嘧啶/亚叶酸钙+紫杉醇联合化疗双周方案治疗晚期胃癌

背景与目的：近来有临床研究显示紫杉醇(paclitaxel,PTX)可用于治疗胃癌,与5．氟尿嘧啶(5-fluorouracil,5-FU)联合治疗晚期胃癌疗效显著,不良反应轻。本研究观察5-Fu／亚叶酸钙(1eueovorin,CF) PTX联合化疗双周方案治疗晚期胃癌的临床疗效和不良反应。方法：采用高剂量5-FU／CF PTX深静脉输注方案(CF 200mg／m^2,静滴2小时,第1天;5-FU 500mg／m^2,静脉推注,第1天;5-FU 1500mg／m^2,静滴46小时;PTX90mg／m^2,静脉输注3小时,第1天),化疗方案以每两周为1周期,重复4周期后评定疗效。结果：全组20例均可评价疗效,总有效率为65．0％(13／20),其中完全缓解(CR)率为10.0％(2／20),部分缓解率为55．0％(11／20)。无治疗相关死亡,主要不良反应为口腔炎、手足综合征和脱发。结论：5-FU／CF PTX联合化疗双周方案治疗晚期胃癌缓解率较高、不良反应可耐受,是治疗晚期胃癌安全有效的化疗方案。     

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.     

Anemia is the strongest prognostic factor for outcomes of 5-fluorouracil-based first-line chemotherapy in patients with advanced gastric cancer

Objective: To examine the prevalence of anemia and its impact of hemoglobin (Hgb) levels in predicting outcomes of 5-fluorouracil (FU)-based first-line chemotherapy for patients with advanced gastric cancer (AGC). Methods: We collected data retrospectively from 511 consecutive patients treated with FU-based first-line chemotherapy as a routine clinical practice for AGC and followed up in two centers from 1995 to 2003. FU was given in combination with cisplatin (61%), taxanes (12%), anthracyclines (24%) and/or folinic acid (50%). Results: Hgb values were <10 g/dl in 41%, and patients with baseline Hgb levels <10 g/dl had significantly lower response rates (9%) than patients with Hgb≥10 g/dl (53%; P<0.001). In addition, Hgb<10 g/dl served as a predictor for disease progression (RR, 1.77; 95% CI, 1.42–2.21) and death (RR, 1.85; 95% CI, 1.48–2.32) along with chemotherapy response and performance status. Conclusion: Low baseline Hgb level is a strong and independent prognostic factor for the outcomes of AGC patients receiving FU-based first-line chemotherapy. This results strongly suggest that Hgb level, along with performance status, may be considered as a stratification variable in subsequent studies of AGC.     

Clinical significance of skip metastasis in patients with gastric cancer

Background Metastasis appearing to bypass or skip tiers of lymph nodes (LNs) has been referred to as skip metastasis. The clinical impact of skip metastasis in gastric cancer remains unclear. Methods In patients with gastric cancer, the clinicopathological features and postoperative prognoses of 21 patients with skip metastasis were evaluated and compared with findings in patients with group 1 (N1) or group 2 (N2) LN metastasis. Results Of the 21 patients with skip metastasis, 9 patients had metastasis in the LN along the common hepatic artery (No. 8a), 8 patients had metastasis in the LN along the left gastric artery (No. 7), 2 patients had metastasis in LNs No. 7 and No. 8a, 1 patient had metastasis in the LN at the splenic hilum (No. 10), and 1 patient had metastasis in LN No. 10 and the LN along the splenic artery (No. 11). The mean diameter of the tumors in the patients with skip metastasis was 5.7 ± 2.4 cm, which was significantly smaller than those in the N1 patients (7.9 ± 4.1 cm) and N2 patients (9.3 ± 4.6 cm). The incidence of serosal invasion, lymphatic vessel invasion, and peritoneal metastasis was lower in patients with skip metastasis compared with N2 patients. The 5-year survival rates were 70.2%, 62.0%, and 31.2% in patients with skip metastasis, patients with metastasis in group 1 LNs, and those with metastasis in group 2 LNs, respectively. The prognosis of patients with metastasis in group 2 LNs was significantly worse than that of patients with either skip metastasis (P = 0.0029) or metastasis in group 1 LNs (P < 0.0001). Conclusion Our data indicate that both the clinicopathological characteristics and the prognoses of patients with skip metastasis were similar to those of patients with N1 LN metastasis, but these features were not similar to those in patients with N2 LN metastasis. The sites of skip metastasis presented in the current study may be the key for applying the concept of the sentinel node in gastric cancer.     

FOLFOX4方案治疗晚期胃癌的临床观察

目的:观察FOLFOX4方案治疗国人晚期胃癌的近期疗效和毒副反应。方法:28例晚期胃癌患者,先给予FOLFOX4方案,即:奥沙利铂(L-OHP)85mg/m2静脉点滴2h,d1;亚叶酸钙(CF)200mg/m2静脉点滴,2h,d1、d2;随后氟尿嘧啶(5-FU)400mg/m2静脉推注,d1、d2,5-FU600mg/m2微泵持续静脉滴注22h,d1、d2。2周重复。4个周期后以WHO评价标准评价疗效和毒性。结果:全组28例均可评价,其中完全缓解(CR)2例,部分缓解(PR)14例,稳定(SD)7例,进展(PD)5例,总有效率(CR PR)57.1%。中位肿瘤进展时间(TTP)5.5个月,中位生存时间(MST)为9个月。毒副反应主要是骨髓抑制,白细胞降低发生率达82.1%,其次为胃肠道反应,恶心呕吐发生率78.6%,口腔粘膜炎为21.4%,腹泻35.7%,无Ⅲ/Ⅳ度胃肠道反应;周围神经毒性发生率为46.4%。结论:FOLFOX4方案治疗国人晚期胃癌的近期疗效较好,毒副反应可以耐受,值得进一步研究应用。     

Phase I study of irinotecan and S-1 combination therapy in patients with metastatic gastric cancer

Background Irinotecan plus intravenous 5-fluorouracil with leucovorin is effective against gastrointestinal cancer. S-1 is an oral fluoropyrimidine derivative combining tegafur with the modulators 5-chloro-2,4-dihydroxypyrimidine (a potent dihydropyrimidine dehydrogenase inhibitor), and potassium oxonate (an orotate phosphoribosyl transferase inhibitor), in a molar ratio of 1:0.4:1. S-1 has a high response rate, of about 40%, in advanced gastric cancer. A phase I study was conducted to assess the maximum tolerated dose and the recommended dose of the combination of irinotecan and S-1.Methods Irinotecan was given intravenously over the course of 90min on day 1 and S-1 was given orally from days 1 to 14 of a 21-day cycle. The dose of S-1 was 80mg/m² per day, given in two divided doses. The dose of irinotecan was escalated in a stepwise fashion from 100mg/m² (level 1; n = 3), to 125mg/m² (level 2; n = 3), and 150mg/m² (level 3; n = 6).Results Dose-limiting toxicity did not occur during cycle 1, and the recommended dose for phase II studies was determined to be level 3, which was associated with grade 3 diarrhea in one patient, and with refusal to continue treatment because of prolonged fatigue in two patients. Grade 3 neutropenia developed in one of three patients at level 1 and level 2, and in two of six during cycle 1 of level 3. The recommended dose was determined to be 150mg/m² of irinotecan on day 1 and 80mg/m² per day of S-1 on days 1 to 14 of a 21-day cycle. Five of seven patients with measurable lesions had a partial response.Conclusions A combination of irinotecan and S-1 can be recommended for further phase II studies in patients with gastric cancer.     

Clinical efficacy of bisphosphonate therapy for bone metastasis from breast cancer

Bisphosphonates inhibit osteoclastic bone resorption and are being used as treatment for bone metastases from breast cancer. Intravenous bisphosphonate therapy can significantly reduce skeletal related events (SREs) when administered concurrently with chemotherapy or endocrine therapy. In addition, intravenous bisphosphonate monotherapy is also able to alleviate cancer induced bone pain, and to improve bone metastases in some patients. Oral bisphosphonates are not routinely used for the treatment of bone metastases due to their low bioavailability. However, minodronate, a bisphosphonate 100-fold more potent than pamidronate, is now in phase II clinical studies in Japan, and may alter the role of oral bisphosphonates in the treatment of bone metastasis from breast cancer. The ASCO guidelines recommend that patients with osteolytic bone metastases be treated not with bisphosphonate monotherapy, but with concurrent bisphosphonate and systemic therapy. In addition, it is also recommended that current standards of care for cancer pain, analgesics and radiotherapy, should not be replaced with bisphosphonate therapy.     

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.     

紫杉醇联合氟尿嘧啶和顺铂方案治疗晚期胃癌

目的：观察紫杉醇联合氟尿嘧啶及顺铂（PFC）方案治疗国人晚期胃癌的临床疗效和毒副反应.方法：晚期胃癌患者25例,给予紫杉醇（PTX）50mg/m^2,静滴3小时,第1、8、15天给药;氟尿嘧啶（5-FU）750mg/m^2,持续静脉输注24小时,第1～5天;顺铂（CDDP）20mg/m^2,静脉滴注,第1～5天,28天为1周期.分别化疗2～6周期后按WHO标准评价疗效和毒副反应.结果：全组25例均可评价疗效,获得CR 2例,PR 11例,SD 7例,PD 5例,近期客观有效率52.0%,中位TTP为6.5月.主要毒副反应为骨髓抑制、恶心呕吐和脱发.结论：PFC方案治疗国人晚期胃癌疗效较高,毒副反应轻,多数患者耐受良好,值得推广应用.     

Phase II multicenter trial of docetaxel, epirubicin, and 5-fluorouracil (DEF) in the treatment of advanced gastric cancer: a novel, safe, and active regimen

Background This study evaluated the efficacy and safety of docetaxel, epirubicin, and 5-fluorouracil (5-FU) [DEF] as treatment for locally advanced unresectable or metastatic gastric cancer. Methods Thirty-seven patients participated in the study (median age, 56 years; range, 22–73 years); Eastern Cooperative Oncology Group performance status [PS], 0–2). Docetaxel 75 mg/m² IV (day 1), 5-FU 500 mg/m² IV (days 1–3), and epirubicin 50 mg/m² IV (day 1) were administered every 3 weeks for six cycles. Results In total, 20/37 patients (54%) completed six treatment cycles. Thirteen patients (35%; 95% confidence intervals [CI], 20% to 51%) had an objective response; 1 patient (3%) achieved a complete response and 12 patients (32%) achieved partial responses. Stable disease was observed in 7 patients (19%) and progressive disease in 5 patients (14%). Twelve patients (32%) were unevaluable. Clinical benefit (based on PS, weight gain, and analgesic consumption) was observed in 11 patients (30%). Median follow-up was 41 months (range, 26–53 months), median time to progression was 6.6 months (range, 0.5–29.2 months), median overall survival was 10.7 months (range, 7.0–14.6 months), and 1-year survival was 40%. The regimen was well tolerated. Grade 3–4 febrile neutropenia occurred in 8 patients (22%; 6% of cycles) and grade 3–4 neutropenia in 1 patient (1% of cycles). The most frequent grade 3–4 toxicities were alopecia (11% of cycles), diarrhea (4% of cycles) and vomiting (2% of cycles); grade 1–2 asthenia and fatigue occurred in 43% of cycles. Conclusion DEF is effective in the treatment of advanced gastric cancer, and has a good safety profile. Presented at: 2002 ASCO Meeting (Poster Section): Proc Am Soc Clin Oncol 2002;21:163a and 2002 ESMO Meeting (Poster Section): Ann Oncol 2002;13(Suppl 5):192