Phase I study of weekly (day 1 and 8) docetaxel in combination with capecitabine in patients with advanced solid malignancies

Purpose Capecitabine in combination with docetaxel given every 3 weeks has shown a high degree of activity in a number of tumor types, but at the expense of significant toxicity. To improve the therapeutic index, we evaluated a weekly regimen of docetaxel in combination with capecitabine, and determined the maximum tolerated dose, toxicities and pharmacokinetics of this combination.Patients and methods Patients with advanced solid malignancies were treated with docetaxel on days 1 and 8, and capecitabine, twice daily on days 1–14, of an every-21-day cycle. Pharmacokinetics of docetaxel were assessed on days 1 and 8 of the first cycle of chemotherapy.Results Enrolled in the study were 25 patients. The most frequent toxicities were asthenia, hand-foot syndrome and mucositis. Inability to deliver at least 75% of the planned doses of both drugs during the first two cycles of chemotherapy was noted at dose levels 2, 3 and 4. Dose level 1 (docetaxel 30 mg/m² and capecitabine 825 mg/m² twice daily) is the recommended dose for phase II studies. Five patients experienced a partial response, and eight patients had stabilization of disease. Coadministration of capecitabine did not alter the pharmacokinetics of docetaxel.Conclusion The regimen consisting of docetaxel 30 mg/m² (days 1, 8) and capecitabine 825 mg/m² twice daily (days 1–14) was well tolerated. Capecitabine did not alter pharmacokinetics of docetaxel. Further testing of this regimen in tumor-specific trials, especially gastric, lung and breast cancer, is warranted.Presented at the 39th Annual Meeting of the American Society of Clinical Oncology, May 2003, Chicago, IL.     

Capecitabine in advanced hepatocellular carcinoma: A multicenter experience

BackgroundRecent data suggest a potential activity and a good tolerability of capecitabine in advanced hepatocellular carcinoma (HCC).AimsTo evaluate capecitabine activity and safety in a wide cohort of advanced HCC patients.MethodsRetrospective analysis of 143 capecitabine-treated patients (January 2010 to December 2017) in three centers of the Veneto Oncology Network.ResultsCapecitabine was administered in second and third line, but also in first line instead of sorafenib in Child-Pugh B patients (70%), compromised clinical conditions (14%) or contraindications to antiangiogenetics (16%). Median overall survival (OS) and time to progression (TTP) were 6.9 and 2.8 months, respectively. There were no differences in OS and TTP between the 32 patients treated with non-metronomic scheme (2000 mg/day for 14 days) and the 111 patients treated with metronomic scheme (1000 mg/day) after correction for prognostic factors at baseline with a propensity score analysis. Capecitabine was more active in patients intolerant to sorafenib than in those progressing during treatment (p = 0.024). At least one adverse event (mainly hematological) was experienced by 73% of patients but discontinuation was necessary only in 11 (8%).ConclusionsCapecitabine can be considered an active and safe option in advanced HCC, especially for patients unfit for other treatments.     

Acute coronary syndrome induced by oral capecitabine

A 41-year-old woman who was undergoing oral chemotherapy with capecitabine for metastatic breast cancer presented with recurrent episodes of chest pain associated with electrocardiographic signs of diffuse ST segment elevation. After spontaneous pain relief, the electrocardiogram showed ischemic evolution in the anterior precordial leads. Coronary and ventricular angiography, performed 24 h later, showed normal coronary arteries and normal left ventricular function. After therapy with capecitabine was discontinued, the patient did not experience further episodes of chest pain. After a nine-month follow-up, she remains alive, with a good performance status and without clinical evidence of persistent ischemia.     

A Phase II Study of Gemcitabine and Capecitabine in Advanced Cholangiocarcinoma and Carcinoma of the Gallbladder: A Single-Institution Prospective Study

Aim To determine the clinical benefit response (CBR), time to tumor progression (TTP), overall survival, and effect on quality of life (QOL) of gemcitabine and capecitabine in patients with advanced biliary cancer. Methods Gemcitabine (1000 mg/m² IV over 30 minutes on days 1 and 8) and capecitabine (650 mg/m² orally twice daily for 14 days) were administered and repeated every 21 days. All patients completed the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire and Pancreatic Cancer Module (EORTC QLQ-C30-PAN 26) questionnaire on day 1 of each cycle. Cumulative QOL scores were calculated. The two-stage design required 17 patients to evaluate the confirmed response at nine weeks. Results Twelve patients with a median age of 54 years were enrolled. A median of eight cycles per patient were completed. With a median follow-up of 18.2 months, the CBR (two partial response and five stable disease) was 58% [95% confidence interval (CI) 28–85%]. Four out of seven patients with CBR had no decline in QOL with chemotherapy. The probability of survival at one year was 0.58. Median TTP and overall survival were 9.0 and 14.0 months, respectively. Nine patients had grade 3 or 4 toxicities. There were no treatment-related deaths. Conclusions Gemcitabine and capecitabine at this dose and schedule are well tolerated and effective and may offer clinical benefit and maintain QOL in patients with advanced biliary cancer. This regimen merits further investigation in the neoadjuvant setting.     

多西紫杉醇联合奥沙利铂、卡培他滨治疗晚期胃癌的疗效观察

目的:观察多西紫杉醇联合奥沙利铂、卡培他滨治疗晚期胃癌的临床疗效和毒副反应。方法:选择不能手术或手术后复发的晚期胃癌患者80例,随机分为试验组和对照组,各40例。试验组采用多西紫杉醇60mg·m-2,静脉滴注,第1天;奥沙利铂130mg·m-2,静脉滴注,第1天;卡培他滨800mg·m-2,口服,bid,第1～14天。对照组采用顺铂20mg·m-2,静脉滴注,第1～5天;5-氟尿嘧啶500mg·m-2,静脉滴注,第1～5天。2组均以21d为1个周期。至少2周期后评价疗效及毒副反应。结果:试验组40例患者有38例可评价疗效,有效率为55.3%,中位疾病进展时间(TTP)为6.6个月,中位总体生存时间(OS)为11.3个月。对照组40例均可评价疗效,有效率42.5%,中位TTP为5.1个月,中位OS为8.9个月。2组差异无统计学意义(P>0.05)。毒副反应主要为骨髓抑制、消化道反应、外周神经毒性,大部分患者可以耐受。结论:多西紫杉醇联合奥沙利铂、卡培他滨治疗晚期胃癌疗效肯定,毒副反应可耐受,可作为主要治疗方案。     

卡培他滨单药用于一线治疗后复发乳腺癌疗效观察

目的:探讨卡堵他滨单药1线治疗后复发晚期乳腺癌的近期疗效.方法:全组27例1线治疗后复发的乳腺癌,卡培他滨2500 mg/(m2·d),分早晚2次口服,连服14天,21天为1个周期,治疗至少2个周期后评价疗效及不良反应.结果:24例可评价疗效,全组无完全缓解(CR),部份缓解(PR)7例(29.1%),稳定(SD)10例(41.8%),进展(PD)7例(29.1%),总有效率为29.1%.主要的不良反应为手足综合征(54.1%)、恶心呕吐(29.1%).结论:卡培他滨对经蒽环类、紫杉类等药物治疗后复发的晚期乳腺癌仍有较好疗效,且不良反应小,耐受性好,可作为复发的晚期乳腺癌的二线治疗方案.     

吉西他滨联合卡培他滨治疗进展期胆道癌37例回顾性分析

目的 回顾性分析吉西他滨联合卡培他滨治疗进展期胆道癌患者的的疗效和安全情况.方法 该科自2006年1月～ 2010年1月共入选37例患者,均为进展期胆道癌患者.口服卡培他滨650mg/m2,2次/d,共14 d;吉西他滨1 000mg/m2在1d和8d静脉滴注,21d为1个周期,2个周期后评价疗效.结果 全组37例患者均可评价疗效.其中未见完全缓解患者,部分缓解率为30％(11/37),稳定49％(18/37),进展22％(8/37).中位进展时间7.2个月(4.2～ 11.9,95％CI),中位生存时间11.3个月(6.1 ～21.9,95％CI).无治疗相关死亡,常见毒性反应是外周血粒细胞下降、血小板减少、轻度贫血、消化道反应、疲劳及偶发的腹泻和皮疹.结论 吉西他滨联合卡培他滨方案治疗进展期胆道癌具有显著的抗肿瘤活性和较温和的毒性反应,可使进展期胆道癌患者受益,值得进一步研究和推广.     

卡培他滨联合伊立替康二线治疗晚期胰腺癌的临床研究

目的:观察卡培他滨联合伊立替康方案二线治疗晚期胰腺癌的疗效和毒性反应。方法:16例既往接受过基于吉西他滨的方案化疗失败的胰腺癌患者,给予卡培他滨1 000 mg/m2口服,2次/d,第1-14天;伊立替康150 mg/m2,静脉滴注,第1天,每4周重复。完成2个周期及以上评价。结果:16例患者中无达到完全缓解及部分缓解者,9例(56.3%)病情稳定,7例(43.8%)病情进展,疾病控制率56.3%;临床获益率31.2%;中位无进展生存12周;中位生存期4个月;血液学毒性发生率75%,其中3～4度白细胞下降的发生率16.7%,3～4度血小板下降发生率16.7%;腹泻发生率41.7%。1例出现3度腹泻,恶心、呕吐发生率50%,无化疗相关死亡。结论:卡培他滨联合伊立替康方案用于吉西他滨方案化疗失败的晚期胰腺癌总体临床耐受性好,可以改善患者生活质量,主要不良反应是血液学毒性和腹泻。     

吉西他滨联合卡培他滨治疗晚期三阴乳腺癌的临床研究

目的探讨吉西他滨联合卡培他滨治疗晚期三阴乳腺癌（TNBC）的临床疗效及毒性反应情况。方法40例TNBC患者给予吉西他滨联合卡培他滨治疗方案,吉西他滨1g／m2静脉滴注,d1、8;卡培他滨1g／m2口服,2次／d,d1～d14。以上治疗方案3w为1个周期。化疗前给予地塞米松、格拉司琼止吐,化疗4个周期后评价临床疗效及毒性反应。结果本组完全缓解（cR）2例,部分缓解（PR）16例,稳定（sD）14例,进展（PD）8例,总有效率（RR）为45．0％。所有患者均随访至2012年12月,失访3例,中位肿瘤进展时间（TTP）为6．1个月。主要毒性反应包括骨髓抑制、手足综合征,次要毒性反应包括腹泻、恶心、呕吐、口腔炎、发热和脱发。结论吉西他滨联合卡培他滨治疗TNBC近期效果满意,毒性反应可耐受。     

XELOX versus FOLFOX6 as an adjuvant treatment in colorectal cancer: an economic analysis

ABSTRACT

Objectives: An economic analysis (based on interim data from a long-term, randomised, multi-centre, controlled, clinical trial) to evaluate chemotherapy with XELOX (capecitabine/oxaliplatin) versus FOLFOX6 (5Fluorouracil/leucovorin/oxaliplatin) as an adjuvant treatment for high risk colorectal cancer patients in Greece.

Methods: As survival rate was the same in the two arms, a cost-minimisation analysis was carried out, from the perspectives of the National Health Service (NHS), Social Insurance Funds (SIF) and patients in Greece. Patient data were combined with 2008 unit prices to estimate the total cost of patient care, the patients’ travelling expenditure and their productivity losses. Raw data were bootstrapped 5000 times in order to allow statistical testing.

Results: From an NHS perspective, the mean chemotherapy cost was €8762 with FOLFOX6 and €9713 with XELOX; costs of administration and hospitalisations were €5154 and €1050, respectively. Total treatment cost with FOLFOX6 reached €17?480 and with XELOX €12?525, a difference of €4955 (p?<?0.001) in favour of the latter therapy. From an SIF perspective, the total cost of treatment was €16?240 with FOLFOX6 and €12?617 with XELOX, a reduction of €3623 (p?<?0.001) with the latter therapy. Mean patient travelling cost was €184 with FOLFOX6 and €80 with XELOX, a difference of €104 (p?<?0.001). Mean productivity loss was €100 with FOLFOX6 and €31 with XELOX, a difference of €69 (p?<?0.001).

Conclusions: Chemotherapy combining oral capecitabine and oxaliplatin reduces total treatment cost for the Greek National Health Service and Social Insurance Funds, mainly through a reduction in the cost of administration. From patients’ perspective, it reduces travelling expenditure and productivity losses. Therefore, this combination may be a cost-effective approach for the management of colorectal cancer patients who have had surgery in Greece. This is an analysis alongside a clinical trial, and should be interpreted in this specific context in which it was undertaken.