Capecitabine “metronomic” chemotherapy for palliative treatment of elderly patients with advanced gastric cancer after fluoropyrimidine-based chemotherapy

We aimed to study the efficacy and safety of metronomic capecitabine in pretreated elderly patients with advanced gastric cancer. Eligible patients with advanced gastric cancer were treated with capecitabine at a fixed dose 1,000 mg daily (days 1–28 continuously, every 5 weeks) until disease progression or significant toxicity. Tumor response was assessed every 10 weeks by computed tomography scan using Response Evaluation Criteria in solid tumors. In total, 45 patients were enrolled, of whom 43 were evaluated for efficacy and 45 for safety. A median of 3 cycles (range 1–12) were administered. Metronomic chemotherapy had a disease control rate (DCR) at 8 weeks of 51.1% (95% CI 25.7–67.8), and the objective response rate was 20.9% (95% CI 13.1–38.5, 9 of 43 assessable patients). The median time-to-progression and median overall survival were 3.6 months (95% CI: 3.2–4.0 months) and 7.6 months (95% CI 7.0–8.2 months), respectively. Grade II neutropenia and thrombocytopenia were observed in 13.3 and 2.2% of patients, respectively. Grade II/III nonhematological toxicities included diarrhea (4.4%), stomatitis (13.4%), and hand–foot syndrome (15.5%). No grade IV toxicity, neutropenic fever or treatment-related deaths occurred. Metronomic capecitabine was effective and well tolerated as palliative treatment in elderly patients with advanced gastric cancer after fluoropyrimidine-based chemotherapy.     

奥沙利铂联合卡培他滨二线治疗晚期胃癌临床疗效观察

 目的 观察奥沙利铂（L-OHP）联合卡培他滨（商品名：希罗达）二线治疗晚期胃癌的临床疗效和毒副作用。方法 晚期复治性胃癌26例，L-OHP 130 mg／m2，加入5 %葡萄糖注射液500 ml中静脉滴注2 h，第1天；卡培他滨1000 mg／m2，2次／d口服，第1～14天；28 d为1周期，连用2个周期后评价疗效。结果 25例可评价疗效，完全缓解（CR）1例，部分缓解（PR）7例，稳定（SD）5例，进展（PD）12例，客观有效率32.0 %，中位疾病进展时间为5.3个月（3～9个月），1年生存率29.5 %。所有患者均可评价毒副反应，主要为骨髓抑制、消化道副反应和神经毒性，均为可逆性。结论 L-OHP联合卡培他滨二线治疗晚期胃癌疗效肯定，毒副作用小，值得临床推广及进一步研究。     

卡培他滨节拍化疗在晚期三阴性乳腺癌维持治疗中的疗效观察北大核心

目的:探讨卡培他滨节拍化疗在晚期三阴性乳腺癌患者维持治疗中的近远期疗效、生活质量以及不良反应。方法:将经联合化疗有效的58例晚期三阴性乳腺癌患者随机分为卡培他滨节拍化疗组和卡培他滨常规剂量组两组,每组患者各29例。节拍化疗组患者给予卡培他滨节拍化疗,常规剂量组患者给予常规剂量卡培他滨化疗。治疗2个月后评价近期疗效,每个月评价不良反应,并统计两组患者的中位疾病进展时间、中位生存时间、1年生存率、2年生存率和生活质量的变化。结果:58例患者均可评价疗效。节拍化疗组患者中CR 0例,PR 5例,SD 22例,PD 2例,客观缓解率(ORR)和疾病控制率(DCR)分别为17.2%和93.1%;常规剂量组患者中CR 0例,PR 6例,SD 20例,PD 3例,客观缓解率(ORR)和疾病控制率(DCR)分别为20.7%和89.7%。两组患者的ORR和DCR相比差异无统计学意义(P>0.05)。节拍化疗组患者的中位肿瘤无进展生存时间(PFS)为7.1个月,与常规剂量组患者(6.9个月)比较,差异无统计学意义(P>0.05);节拍化疗组患者的1年、2年生存率分别为72.4%、58.6%,与常规剂量组患者(69.0%、55.2%)比较,差异无统计学意义(P>0.05)。生活质量改善方面,节拍化疗组患者显著优于常规剂量组患者(P<0.05);节拍化疗组患者的主要不良反应为骨髓抑制、消化道反应和手足综合征等,均以Ⅰ-Ⅱ度为主,均可耐受,常规剂量组患者的消化道反应、骨髓抑制、手足综合征等不良反应的发生率和严重程度均显著高于节拍化疗组(P<0.05)。结论:卡培他滨节拍化疗作为晚期三阴性乳腺癌患者的维持治疗,其近远期疗效与常规剂量维持化疗相当,同时可提高患者生活质量,不良反应轻且发生率低,值得临床推广应用。     

卡培他滨联合沙利度胺节拍化疗治疗晚期结直肠癌的疗效观察及其对生活质量的影响

目的:探讨卡培他滨联合沙利度胺对晚期结直肠癌进行节拍化疗的临床疗效及其对患者生活质量的影响.方法:选取50例晚期结直肠癌患者采用卡培他滨联合沙利度胺进行节拍化疗,分别于节拍化疗前及化疗2周期后检测外周血清中CEA、CA19-9水平,并评估疗效及患者生活质量.结果:总有效率(RR)为26.0％,临床获益率为(CBR)为74.0％.行节拍化疗后外周血中CEA及CA19-9水平均较化疗前明显降低(P=0.014,P=0.004).生活质量方面,经节拍化疗后患者社会功能、躯体功能、情绪功能较治疗前明显改善,疲乏、疼痛症状及睡眠障碍较前明显减轻,角色功能、认知功能及食欲减退情况无明显改变.结论:卡培他滨联合沙利度胺节拍化疗是治疗晚期结直肠癌的一种有效、安全、经济、依从性高的手段,能够提高患者生存质量,值得进一步研究及临床推广.     

Phase I/II study of gefitinib and capecitabine in patients with colorectal cancer

Objective The objectives of this phase I/II study were to determine the maximum tolerated dose (MTD), characterise the principal toxicities in the phase I part and assess the efficacy in the phase II part of gefitinib, an oral selective inhibitor of the epidermal growth factor receptor, in combination with capecitabine in patients with advanced colorectal cancer (CRC). Methods and patients Patients with advanced CRC were treated with gefitinib administered daily for 21 days and capecitabine administered twice daily for 14 days of a 21-day cycle. The dose levels of gefitinib (mg) and capecitabine (mg/m² bid) assessed were 250/1000 and 250/ 1250. An expanded cohort was enrolled at the MTD to better characterise toxicity and efficacy. A total of 32 previously treated patients were accrued. In the phase I part 10 subjects were treated, with one dose-limiting toxicity. Overall 26 patients were treated at the MTD of the combination, which was gefitinib 250 mg/day and capecitabine 1250 mg/m² twice daily. Results The most frequent treatment-related adverse events included asthenia, diarrhoea, nausea, rash and anorexia. The incidence profile was very similar in phases I and II. No objective responses were documented but 53% of the patients achieved stable disease as best response to therapy. Conclusions Capecitabine 1250 mg/m² twice daily 14 of 21 days and gefitinib at 250 mg/day can be safely administered in combination. The combination is relatively well tolerated. There were no objective responses, although an interesting stabilisation rate was documented, in previously treated advanced CRC patients.     

A phase I-II study of postoperative capecitabine-based chemoradiotherapy in gastric cancer

BACKGROUND: The Intergroup 0116 randomized study showed that postoperative 5-fluorouracil-based chemoradiotherapy improved locoregional control and overall survival in patients with gastric cancer. We hypothesized that these results could be improved further by using a more effective, intensified, and convenient chemotherapy schedule. Therefore, this Phase I-II dose-escalation study was performed to determine the maximal tolerated dose and toxicity profile of postoperative radiotherapy combined with concurrent capecitabine. PATIENTS AND METHODS: After recovery from surgery for adenocarcinoma of the gastroesophageal junction or stomach, all patients were treated with capecitabine monotherapy, 1,000 mg/m2 twice daily for 2 weeks. After a 1-week treatment-free interval, patients received capecitabine (650-1,000 mg/m2 orally twice daily 5 days/week) in a dose-escalation schedule combined with radiotherapy on weekdays for 5 weeks. Radiotherapy was delivered to a total dose of 45 Gy in 25 fractions to the gastric bed, anastomoses, and regional lymph nodes. RESULTS: Sixty-six patients were treated accordingly. Two patients went off study before or shortly after the start of chemoradiotherapy because of progressive disease. Therefore, 64 patients completed treatment as planned. During the chemoradiotherapy phase, 4 patients developed four items of Grade III dose-limiting toxicity (3 patients in Dose Level II and 1 patient in Dose Level IV). The predefined highest dose of capecitabine, 1,000 mg/m2 twice daily orally, was tolerated well and, therefore, considered safe for further clinical evaluation. CONCLUSIONS: This Phase I-II study shows that intensified chemoradiotherapy with daily capecitabine is feasible in postoperative patients with gastroesophageal junction and gastric cancer.     

Preliminary results of capecitabine metronomic chemotherapy in operable triple-negative breast cancer after standard adjuvant therapy – A single-arm phase II study

PurposeThe aim of this study is to investigate efficacy and toxicity of 1 year of capecitabine metronomic therapy preceded by standard adjuvant chemotherapy in triple-negative breast cancer (TNBC) patients.MethodsBetween June 2010 and February 2012, 19 women with pathologically proven operable TNBC, who had received standard adjuvant chemotherapy before were enrolled. Patients received 1 year of oral capecitabine metronomic therapy (650 mg/m², twice every day), after standard adjuvant chemotherapy and radiotherapy if indicated. The primary endpoints of this study were disease-free survival rates (DFS) and safety profile. Secondary end point was overall survival (OS).ResultsThe maximal follow-up was 46.6 months with a median of 30.1 months ±11.525 (95% CI; 28.5–33.5 months). The median DFS was 41.7 months ±2.7 (95% CI; 36.5–46.9). No one developed locoregional recurrence. The actuarial rate of DFS was 88.8% and 82.05% at 2 and 3 years, respectively. At the time of the analyses, no patients had died and the median OS was not reached. Treatment-related adverse events were manageable with only 1 patient (5.3%) suffering from Grade 3/4 hand-foot syndrome and another 1 patient (5.3%) suffering from Grade 3 diarrhea. No Grade 3/4 hematologic toxicity was recorded. All patients received full doses of capecitabine throughout the study and dose reduction was not required in any of our patients.ConclusionOne year of capecitabine metronomic therapy preceded by standard adjuvant chemotherapy, is active and well-tolerated in TNBC patients previously treated with standard adjuvant chemotherapy.     

奥沙利铂联合卡培他滨治疗晚期胃癌的临床分析

目的:研究奥沙利铂(LOHP)联合卡培他滨(CAPE)治疗进展及转移性胃癌的疗效和毒性作用。方法:LOHP85mg/m2,静滴2小时,第1、8天,CAPE2500mg/m2,第1～14天,每3周重复,行2周期后判断疗效。结果:19例病人中完全有效3例(15.8%),部分有效7例(36.8%),稳定5例(26.3%),进展4例(21.1%),总有效率52.6%,中位生存期11月,毒性反应以手足综合症、神经毒性反应、骨髓抑制为主,无化疗相关死亡。结论:奥沙利铂联合卡培他滨治疗晚期胃癌疗效肯定,毒性反应可耐受。     

奥沙利铂联合卡培他滨治疗晚期胃癌的临床观察

目的 评价奥沙利铂联合卡培他滨（XELOX）方案治疗晚期胃癌的疗效和不良反应。方法56例晚期胃癌患者予奥沙利铂130mg／m^2,第1天,静脉滴注;卡培他滨1000mg／m^2每天口服2次,第1～14天,21天为1个周期。至少治疗2周期评价疗效。结果CR0例,PR27例,SD13例,PD16例,总有效率为48．2％,疾病控制率（DCR）为71．4％。其中初治组总有效率为60．0％,明显高于复治组的34．6％（P〈0．05）。不良反应主要为骨髓抑制、恶心呕吐、神经毒性。结论XELOX方案治疗晚期胃癌疗效肯定,安全性好,不良反应可耐受,值得临床进一步研究。     

Capecitabine and doxorubicin combination chemotherapy as salvage therapy in pretreated advanced gastric cancer

Purpose The aim of this study was to evaluate the activity and the safety of a combination regimen of capecitabine and doxorubicin as salvage chemotherapy in advanced gastric cancer patients who had undergone one or two prior chemotherapy regimens. Methods Patients received capecitabine, 2,500 mg/m²/day PO for 14 days (D1–14) and doxorubicin, 30 mg/m² IV on day 1 every 3 weeks until disease progression. The response was evaluated according to RECIST criteria, and the toxicity was evaluated by NCI-CTC (version 2.0). Results Forty-five patients were enrolled. Twenty-six patients were treated as second-line chemotherapy and the remaining patients as third-line chemotherapy. A total of 152 cycles of chemotherapy (median 2, range 1–12) were administered. Median dose intensities of capecitabine and doxorubicin were 11,326 and 9.6 mg/m²/week, respectively. The overall response rate was 6.7% (95% CI, 4.1–12.5%) and the disease control rate was 46.7% (95% CI, 28.6–87.1%) according to an intent-to-treat analysis. The median progression-free survival was 11.3 weeks (95% CI, 5.6–16.7 weeks). The median overall survival was 29.1 weeks (95% CI, 18.3–39.9 weeks) with one-year survival rate of 24%. Severe (grade III/IV) hematologic and non-hematologic toxicity was uncommon and included nausea/vomiting in five (11.1%), neutropenia in two (4.4%), anemia in one (2.2%), and hand-foot syndrome in one patient (2.2%). Conclusions The combination of capecitabine and doxorubicin is a feasible salvage regimen in advanced pre-treated gastric cancer.     

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.     

晚期胃癌一线XELOX方案化疗后卡培他滨维持治疗的临床观察

目的 探讨晚期胃癌一线奥沙利铂联合卡培他滨（XELOX方案）化疗后卡培他滨维持治疗的疗效和安全性。方法 84例晚期胃癌经一线XELOX方案化疗有效后分为治疗组与对照组,每组42例;治疗组采用卡培他滨维持化疗至疾病进展或出现不可耐受的不良反应,对照组随访观察。结果 治疗组中位无进展生存时间（progression free survival,PFS）为9.6个月,对照组为6.8个月（P<0.05）;治疗组中位总生存时间（overall survival,OS）为13.5个月,对照组为11.6个月（P<0.05）。主要不良反应有血液学毒性、胃肠道反应、手足综合征、口腔黏膜炎、周围神经毒性等,经对症治疗后均好转,无治疗相关性死亡。结论 晚期胃癌一线XELOX方案化疗有效后卡培他滨维持治疗可延长PFS及OS,不良反应可耐受。     

A phase I study of EKB-569 in combination with capecitabine in patients with advanced colorectal cancer

PURPOSE: To determine the maximum tolerated dose (MTD), characterize the principal toxicities, and assess the pharmacokinetics of EKB-569, an oral selective irreversible inhibitor of the epidermal growth factor receptor tyrosine kinase, in combination with capecitabine in patients with advanced colorectal cancer. EXPERIMENTAL DESIGN: Patients were treated with EKB-569 daily for 21 days and capecitabine twice daily for 14 days of a 21-day cycle. The dose levels of EKB-569 (mg/day) and capecitabine (mg/m(2) twice daily) assessed were 25/750, 50/750, 50/1,000 and 75/1,000. An expanded cohort was enrolled at the MTD to better study toxicity and efficacy. Samples of plasma were collected to characterize the pharmacokinetics of the agents. Treatment efficacy was assessed every other cycle. RESULTS: A total of 37 patients, the majority of whom had prior chemotherapy, received a total of 163 cycles of treatment. Twenty patients were treated at the MTD, 50 mg EKB-569, daily and 1,000 mg/m(2) capecitabine twice daily. Dose-limiting toxicities were diarrhea and rash. No patients had complete or partial responses but 48% had stable disease. The conversion of capecitabine to 5-fluorouracil was higher for the combination of EKB-569 and capecitabine (321+/-151 ng*h/mL) than for capecitabine alone (176+/-62 ng*hours/mL; P=0.0037). CONCLUSION: In advanced colorectal cancer, 50 mg EKB-569 daily can be safely combined with 1,000 mg/m(2) capecitabine twice a day. A statistically significant increase in plasma levels of 5-fluorouracil for the combination of EKB-569 and capecitabine may be due to the single-dose versus multiple-dose exposure difference, variability in exposure or a potential drug interaction.     

A pilot phase II study of capecitabine in advanced or recurrent gastric cancer

OBJECTIVES: To evaluate the efficacy and safety of capecitabine in patients with advanced or recurrent gastric cancer, we conducted a pilot phase II study in Japan. METHODS: Patients with advanced or recurrent gastric cancer were given oral capecitabine 828 mg/m(2) twice daily for 3 weeks, followed by 1 week of no treatment. Two or more cycles were administered. From July 1996 to December 1997, 32 patients were enrolled in the study. The response to capecitabine was evaluated in 31 patients, excluding 1 found to be ineligible. RESULTS: The overall response rate was 19.4% (6/31, 95% confidence interval: 7.5-37.5%). The median duration of response was 124.5 days, the median time to disease progression 85.0 days, and the median survival time 247.5 days. Drug-related adverse events of grade 3 or higher were infrequent: in 2 patients (6.3%) total bilirubin concentration increased, and 1 patient (3.1%) each had elevation of GOT, anemia, lymphopenia, increased creatinine, and hand-foot syndrome. No patient had gastrointestinal toxicity of grade 3 or higher. CONCLUSION: Capecitabine was suggested to be safe and effective in the treatment of advanced or recurrent gastric cancer. Further phase II studies of capecitabine on a large scale are warranted.     

TX方案治疗铂类治疗失败的进展期胃癌的临床疗效分析

目的:评价紫杉醇联合卡培他滨作为含铂类药物治疗失败的进展期胃癌二线治疗的疗效及安全性。方法:既往接受FP或者FOLFOX4方案化疗的进展期胃癌患者36例,采用TX方案化疗,紫杉醇145mg/m2静脉滴注3h,d1;卡培他滨2000mg/m2,分2次口服,d1-14,21天为一个周期,随访观察疗效,不良反应,进展时间和生存期。结果:36例患者共接受142个周期的化疗,中位化疗周期数4个。全组36例患者中有35例可评价疗效及不良反应,其中8例部分缓解,有效率为22.8%(95%CI:8.2%-37.5%)。中位进展时间和生存时间分别为4.8个月(95%CI:2.9-6.2)和8.1个月(95%CI:6.4-12.7)。Ⅲ/Ⅳ度不良反应主要为骨髓抑制、手足综合征及脱发。结论:紫杉醇联合卡培他滨方案二线治疗进展期胃癌疗效确切,不良反应小,尤其对老年患者耐受性好。     

紫杉醇联合卡培他滨一线治疗晚期胃癌的临床观察

目的　观察紫杉醇联合卡培他滨一线治疗晚期胃癌的疗效和毒副反应。方法　晚期胃癌患者２０例,给予紫杉醇８０ｍｇ／ｍ２静脉滴注,第１、８天;卡培他滨１０００ｍｇ／ｍ２,分早晚各口服１次,第１～１４天;２１天为１周期。每２周期评价疗效。结果　１９例可评价疗效,获ＣＲ１例,ＰＲ７例,总有效率（ＲＲ）为４２.１％。中位无进展生存期和总生存期分别为４.８个月和９.７个月,１年生存率为３６.８％。主要的毒副反应为血液学毒性、脱发和手足综合症。结论　紫杉醇联合卡培他滨治疗晚期胃癌安全、有效,值得临床进一步应用。     

Phase II study of capecitabine and cisplatin as first-line combination therapy in patients with gastric cancer recurrent after fluoropyrimidine-based adjuvant chemotherapy

To evaluate the efficacy and safety of capecitabine and cisplatin in patients with recurrent gastric cancer after fluoropyrimidine-based adjuvant therapy. Patients with histologically confirmed and measurable advanced gastric cancer that had relapsed after fluoropyrimidine-based adjuvant chemotherapy received oral capecitabine (1250 mg m(-2) twice daily, days 1-14) and intravenous cisplatin (60 mg m(-2) over 1 h, day 1) every 3 weeks. In total, 32 patients were enrolled, of whom 30 were evaluable for efficacy and 32 for safety. A median of 5 cycles (range 1-10) was administered. One patient achieved a complete response and eight had partial responses, giving an overall response rate of 28% (95% CI, 13-44%). The median time to progression and median overall survival were 5.8 months (95% CI, 4.1-7.5 months) and 11.2 months (95% CI, 5.5-16.9 months), respectively. Grade 3 neutropenia and thrombocytopenia were observed in 38 and 6% of patients, respectively. Grade 2/3 nonhaematological toxicities included diarrhoea (19%), stomatitis (19%) and hand-foot syndrome (31%). No grade 4 toxicity, neutropenic fever or treatment-related deaths occurred. Capecitabine in combination with cisplatin was effective and well tolerated as first-line treatment in patients with recurrent gastric cancer after fluoropyrimidine-based adjuvant chemotherapy.     

Clinical outcome of patients with docetaxel-resistant hormone-refractory prostate cancer treated with second-line cyclophosphamide-based metronomic chemotherapy

For patients with docetaxel-resistant hormone-refractory prostate cancer (HRPC) no standard chemotherapeutic treatment exists. In this study, we evaluate the efficacy of cyclophosphamide (CP)-based metronomic chemotherapy in this patient population. Patients with metastatic HRPC with disease progression under docetaxel-based chemotherapy were eligible. The primary endpoint was prostate-specific antigen (PSA) response. Secondary endpoints were survival and toxicity. Low-dose CP (50 mg/d) and dexamethasone (1 mg/d) were administered orally in a metronomic manner. Treatment was continued until disease progression or intolerable side effects occurred. Seventeen patients were enrolled in this study. The median follow-up was 12 weeks (range: 4–60). Median age was 68 years (range: 42–85). Median PSA at study entry was 134 ng/ml (range: 46.0–6554). Nine patients had a PSA response (median 44.4%), four patients ≥50% and five patients <50%. Eight patients had a PSA progression. Overall survival was 24 months. Five patients reported a decrease in bone pain after 4 weeks' treatment. No grade 3 and 4 toxicities were noted. In this study, low-dose metronomically administered CP demonstrated efficacy as a second-line treatment in patients with docetaxel-resistant HRPC. The treatment was well tolerated and almost without toxicity. Further advantages of low-dose CP were its convenient oral administration, dosing schedule, low cost, and low-toxicity profile. These attributes in combination with immunoregulatory and antiangiogenic potentials make CP also a prime candidate for combination with other treatment regimens.     

First-line treatment with oxaliplatin and capecitabine in patients with advanced or metastatic oesophageal cancer: a phase II study

This phase II study assessed the safety and efficacy of oxaliplatin and capecitabine in patients with advanced oesophageal cancer. Fifty-one eligible patients received oxaliplatin 130 mg m(-2) intravenously on day 1 and capecitabine 1000 mg m(-2) orally twice daily on days 1 to 14 in a 21-day treatment cycle as first-line treatment for advanced oesophageal cancer. Grade 3 neutropenia was seen in one patient and anaemia in another patient. No grade 4 haematological toxicities were observed. Grade 4 non-haematological toxicity (lethargy) occurred in one patient (2%). Grade 3 non-haematological toxicity was seen in 14 (27%) patients (vomiting and polyneuropathy (8%); nausea (6%); lethargy and hand-foot syndrome (4%); and anorexia, diarrhoea, and hyperbilirubinaemia (each in one patient)). In 22% of the patients, toxicity was the reason for stopping the treatment. The overall response rate was 39%. The median overall survival was 8 months; the 1-year survival rate was 26%. In the quality of life (QoL) analysis, the emotional well-being improved during treatment, but the physical functioning scores declined. The fatigue score on the symptom scales increased. Overall, the global QoL score did not change during treatment. In conclusion, the activity of oxaliplatin and capecitabine is comparable with other chemotherapy regimens in advanced oesophageal cancer with a low frequency of grade 3/4 toxicity. Because this treatment can be given on an outpatient basis, it is probably less toxic than cisplatin-based therapy and preserves QoL during treatment, it is a viable treatment option in patients with advanced oesophageal cancer.     

Phase II Trial of Fulvestrant With Metronomic Capecitabine for Postmenopausal Women With Hormone Receptor-Positive,HER2-Negative Metastatic Breast Cancer

BackgroundIn this phase II study, we explored efficacy and toxicity of combined endocrine and low-dose metronomic chemotherapy therapy consisting of fulvestrant and capecitabine in estrogen and/or progesterone receptor-positive, HER2-negative MBC.Patients and MethodsPatients with ≤ 1 previous hormonal treatment in the metastatic setting received an injection fulvestrant loading dose 500 mg on day 1, 250 mg on days 15 and 29 followed by 250 mg every 28 days along with continuous oral capecitabine in divided doses. The total fixed daily dose of capecitabine was either 1500 mg or 2000 mg, depending on the patient’s weight (< 80 kg vs. ≥ 80 kg). Primary end points were PFS and TTP. Toxicity was assessed by continuous evaluations of treatment-emergent adverse events (AEs) and changes from baseline in laboratory values.ResultsForty-one women, with a mean age of 64.5 years, were enrolled. Patients completed a median of 11 monthly treatment cycles. Median PFS was 14.98 months (95% confidence interval [CI], 7.26-upper limit [UL] not estimated) and median TTP was 26.94 months (95% CI, 7.26-UL not estimated). Median overall survival was 28.65 months (95% CI, 23.95-UL not estimated). Treatment was well tolerated with < 10% Grade 3 palmar-plantar erythrodysesthesia. Overall, the most frequent AEs were palmar-plantar erythrodysesthesia, fatigue, and nausea.ConclusionFulvestrant with metronomic capecitabine demonstrates substantial activity in hormone receptor-positive MBC and is well tolerated. Combined chemoendocrine approaches should be further explored considering the low toxicity of the combination with meaningful TTP.