Evolving strategies for the management of hand-foot skin reaction associated with the multitargeted kinase inhibitors sorafenib and sunitinib

The multitargeted kinase inhibitors (MKIs) sorafenib and sunitinib have shown benefit in patients with renal cell carcinoma, hepatocellular carcinoma (sorafenib), and gastrointestinal stromal tumor (sunitinib). Their efficacy in other malignancies is currently being investigated because of their broad range of activity. The effectiveness of these drugs is somewhat diminished by the development of a variety of toxicities, most notably hand-foot skin reaction (HFSR). Although HFSR does not appear to directly affect survival, it can impact quality of life and lead to MKI dose modification or interruption, potentially limiting the antitumor effect. Currently, no standard guidelines exist for the prevention and management of MKI-associated HFSR. To address this issue, an international, interdisciplinary panel of experts gathered in January 2008 to discuss and evaluate the best-practice management of these reactions. Based on these proceedings, recommendations for the management of HFSR have been provided to offer patients the best possible quality of life while taking these drugs and to optimize the patient benefit associated with MKI therapy.     

The Hand‐Foot Skin Reaction and Quality of Life Questionnaire: An Assessment Tool for Oncology

Background.

Skin toxicity (hand-foot syndrome/hand-foot skin reaction, HFS/R) related to antineoplastic therapy is a significant issue in oncology practice, with potentially large impacts on health-related quality of life (HRQL).

Materials and Methods.

A patient-reported questionnaire, the hand-foot skin reaction and quality of life (HF-QoL) questionnaire was developed to measure the HFS/R symptoms associated with cancer therapeutic agents and their effect on daily activities. The validity and reliability of the HF-QoL questionnaire was tested in a randomized trial of capecitabine with sorafenib/placebo in 223 patients with locally advanced/metastatic breast cancer. Other measures completed included patient ratings of condition severity, the Functional Assessment of Cancer Therapy-Breast cancer (FACT-B), and the clinician-rated National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 3.0, hand-foot skin reaction grade. The psychometric properties of the HF-QoL tested included structural validity, internal consistency, construct validity, discriminant validity, and responsiveness. Finally, the minimal clinically important difference (MCID) was estimated.

Results.

The HF-QoL instrument comprises a 20-item symptom scale and an 18-item daily activity scale. Each scale demonstrated excellent measurement properties and discriminated between NCI-CTCAE grade and patient-rated condition severity with large effect sizes. The daily activity scale had excellent internal consistency and correlated with the FACT-B and HF-QoL symptom scores. Both HF-QoL scale scores increased linearly with increasing patient-rated condition severity. The MCIDs were estimated as 5 units for daily activities and 8 units for symptoms mean scores.

Conclusion.

The HF-QoL was sensitive to symptoms and HRQL issues associated with HFS/R among participants treated with capecitabine with and without sorafenib. The HF-QoL appears suitable for assessing the HRQL impairment associated with HFS/R to cancer therapies.

Implications for Practice:

Skin toxicity related to anticancer therapies is a significant issue in oncology practice. Several newer agents, as well as older therapies, are associated with the skin toxicity known as hand-foot skin reaction (HFSR) or hand-foot syndrome (HFS). This study describes the development and validation of a brief, patient-reported questionnaire (the hand-foot skin reaction and quality of life questionnaire) supporting its suitability for use in clinical research to aid in early recognition of symptoms, to evaluate the effectiveness of agents for HFS/R treatment within clinical trials, and to evaluate the impact of these treatments on HFS/R-associated patients'' health-related quality of life.     

索拉非尼治疗晚期原发性肝癌的临床观察

目的　观察索拉非尼治疗晚期原发性肝癌的疗效、生活质量以及不良反应。方法　２０例无法手术的原发性肝癌患者口服索拉非尼（４００ｍｇｂｉｄ）,至出现不可耐受的不良反应或连续两次评价为疾病进展,观察客观疗效、无进展生存期（ＴＴＰ）、总生存期（OＳ）、生活质量和不良反应。结果　２０例患者中ＳＤ１５例,ＰＤ５例,中位ＴＴＰ为５.９月（１.５～１５.０个月）,中位ＯＳ为７.７个月（２.０～２１.０个月）。服药期间患者的总体健康状况及五项功能领域得分在第６周时下降,但自第１２周上述功能领域均能稳定在治疗前状态。疼痛及腹泻在治疗过程中持续存在,而乏力、恶心呕吐、失眠、厌食、便秘及经济困难均得以改善。最常见的不良反应是手足皮肤反应,食欲下降和腹泻。结论　索拉非尼用于晚期原发性肝癌患者疗效肯定,不良反应少且多数可耐受,服药期间患者的生活质量能保持稳定。     

多靶点分子靶向治疗在晚期肝细胞肝癌治疗中的应用研究

目的评价多靶点分子靶向治疗药物甲磺酸索拉非尼治疗晚期／进展期肝细胞肝癌的临床疗效和不良反应。方法2007年4月至2008年11月，中国医学科学院肿瘤医院收治的37例晚期／进展期肝细胞肝癌患者，采用多靶点分子靶向治疗药物甲磺酸索拉非尼（多吉美）治疗，起始剂量400mg，口服，每日2次，治疗过程中根据不良反应发生情况调整用量。每6周、12周全面复查1次，评价肝功能变化、治疗效果和不良反应。用SPSS13．0软件统计中位至疾病进展时间和中位总生存时间。结果至2009年2月，37名患者均达到临床评价要求，无中途停药。治疗相关不良反应发生率为84．8％，其中主要不良反应为：手足皮肤反应、腹泻和高血压。2例Ⅲ级手足皮肤反应患者经调整用药剂量后症状缓解，Ⅰ级不良反应和Ⅱ级不良反应患者经过对症处理后症状缓解，未影响治疗。37名患者治疗前及治疗12周后的ALT、TBIL和ALB无明显变化。疾病进展11例，其中死亡8例。经统计学分析，该组患者中位至疾病进展时间66周，中位生存时间72周。结论无法接受局部治疗，或接受局部治疗后肿瘤进展的晚期／进展期肝细胞肝癌患者，使用甲磺酸索拉非尼治疗，无严重不良反应发生，能显著延长无病生存时间和总生存时间。提前干预不良反应的发生是确保疗效的重要手段之一。     

经导管肝动脉化疗栓塞联合索拉非尼治疗中晚期肝细胞癌的临床观察

目的 观察经导管肝动脉化疗栓塞(TACE)联合索拉非尼治疗中晚期肝细胞癌的有效性和安全性.方法 40例已接受过TACE治疗的中晚期肝细胞癌患者口服索拉非尼单药治疗,400mg,2次/d,直至病情进展或出现不可耐受的毒性反应.按照实体瘤疗效评价标准(RECIST)评价疗效,按照美国国立癌症研究所常见毒性事件标准(NCI-CTCAE)评价不良反应.结果 40例中晚期肝细胞癌患者中,获得完全缓解1例,部分缓解7例,疾病稳定19例,疾病进展13例,疾病控制率为67.5%.全组患者的生存时间为1～18个月,1年生存率为54.0%.主要不良反应为手足皮肤反应,其次是腹泻和血小板计数降低.结论 TACE联合索拉非尼治疗中晚期肝细胞癌是有效和安全的.     

Phase I trial of sorafenib in combination with IFN alpha-2a in patients with unresectable and/or metastatic renal cell carcinoma or malignant melanoma.

PURPOSE: To determine the safety, maximum tolerated dose, pharmacokinetics, and efficacy, and to evaluate biomarkers, of the multikinase inhibitor sorafenib plus IFN alpha-2a in advanced renal cell carcinoma (RCC) or melanoma. EXPERIMENTAL DESIGN: Patients received 28-day cycles of continuous, oral sorafenib twice daily and s.c. IFN thrice weekly: sorafenib 200 mg twice daily plus IFN 6 million IU (MIU) thrice weekly (cohort 1); and sorafenib 400 mg twice daily plus IFN 6 MIU thrice weekly (cohort 2); or plus IFN 9 MIU thrice weekly (cohort 3). Tumor response was assessed by Response Evaluation Criteria in Solid Tumors and dynamic contrast-enhanced ultrasonography. RESULTS: Thirteen patients received at least one dose of sorafenib plus IFN (12 RCC; one melanoma). The maximum tolerated dose was not reached [only one dose-limiting toxicity (grade 3 asthenia)]. Most frequently reported drug-related adverse events were grade 2 or less in severity, including fatigue, diarrhea, nausea, alopecia, and hand-foot skin reaction. One (7.7%) RCC patient achieved partial response and eight (61.5%) had stable disease (including the melanoma patient). Good responders assessed by dynamic contrast-enhanced ultrasonography had increased progression-free survival and overall survival, relative to poor responders. IFN had no effect on the pharmacokinetics of sorafenib. There were no significant changes in absolute values of lymphocytes, levels of proangiogenic cytokines, or inhibition of phosphorylated extracellular signal-regulated kinase in T cells or natural killer cells, with combination therapy. CONCLUSIONS: This sorafenib combination was well tolerated, with preliminary antitumor activity in advanced RCC and melanoma patients. There were no drug-drug interactions and the recommended dose for future studies is sorafenib 400 mg twice daily plus IFN 9 MIU.     

The outcome of chemotherapy by sorafenib in advanced hepatocellular carcinoma

We analyzed the treatment outcome and effect of sorafenib in advanced hepatocellular carcinoma. Nine patients were received the therapy of sorafenib between June 2009 and October 2009. The overall incidence of treatment-related adverse events was 87.5%. Grade 3 drug-related adverse events included a hand-foot skin reaction (two patients) and fatigue (one patient). Grade 2 hypertension (three patients), grade 1 diarrhea (two patients) and anorexia (four patients) occurred at this study. The response rate was 0% (CR/PR 0, SD 2, PD 6) and median overall survival length was 101 days. Now there are two patients undergoing the therapy of sorafenib. Effect of sorafenib in advanced hepatocellular carcinoma was not good in this study, and drug-related adverse events had a high rate. However, the continuous treatment was possible with dose modified chemotherapy.     

索拉非尼联合经导管肝动脉化疗栓塞治疗无远处转移的晚期肝细胞癌

目的　观察多靶点分子靶向治疗药物索拉非尼联合经导管肝动脉化疗栓塞（ＴＡＣＥ）治疗不伴远处转移的晚期或进展期肝细胞癌的疗效和不良反应。方法　２００７年４月至２００９年９月,中国医学科学院肿瘤医院收治４５例不伴有远处转移的晚期或进展期肝细胞癌患者,口服索拉非尼治疗,其中１８例联合ＴＡＣＥ（１～５次）,２７例单用索拉非尼。索拉非尼起始剂量４００ｍｇ,每日２次,治疗过程中根据不良反应发生情况调整用量。每２个月评价疗效和不良反应,并随访中位至疾病进展时间（ＴＴＰ）和中位总生存时间（ＯＳ）。结果　至２００９年１２月,４０例患者达到临床评价要求（联合ＴＡＣＥ１８例,单用索拉非尼２２例）。两组不良反应发生率无显著差异,主要治疗相关不良反应为手足皮肤反应、腹泻和高血压。两组患者均无４级严重不良反应。索拉非尼联合ＴＡＣＥ组中位ＴＴＰ为１０.０个月,中位ＯＳ１６.０个月;单用索拉非尼组中位ＴＴＰ为４.５个月,中位ＯＳ５.３个月。两组ＯＳ和ＴＴＰ差异有统计学意义（Ｐ＜０.０１）。结论　病变局限在肝内且不合并远处转移的晚期或进展期肝细胞癌患者,口服索拉非尼联合ＴＡＣＥ不增加并发症发生率,且生存预后改善。     

Cutaneous Squamous Cell Carcinoma and Inflammation of Actinic Keratoses Associated with Sorafenib

Background

Sorafenib-induced dermatologic toxicity is common and consists primarily of dry skin, maculopapular rash, hand-foot skin reaction, and alopecia. Cutaneous squamous cell carcinoma (SCC) and inflammation of actinic keratosis (AK) were reported in 2 patients treated with sorafenib (Lacouture et al), but the scope of this observation has not been evaluated.

Patients and Methods

We reviewed medical records of 131 patients with metastatic renal cell carcinoma treated with single-agent sorafenib at our institution from June 1, 2005, through April 4, 2007.

Results

We identified 7 cases of cutaneous SCC, 2 cases of SCC keratoacanthoma type, 2 cases of focal squamous atypia, and 3 cases of AKs. The time to development of SCC or AK from the start of sorafenib was 9.3 months (median, 6.5 months; range, 0.9-43 months). Ten of these 14 patients discontinued therapy with sorafenib: 7 patients as a result of disease progression, 2 patients as a result of nondermatologic toxicity, and 1 patient as a result of dermatologic toxicity. Four patients are continuing sorafenib therapy at reduced doses because of diarrhea and fatigue. One patient receiving sorafenib at a 25% dose reduction developed a second invasive SCC lesion on his forearm 6 months after the initial resection.

Conclusion

These data suggest that there could be an association between sorafenib therapy and the development of cutaneous SCC and inflammation of AK. This adverse event has important therapeutic implications. Full appraisal of this observation in prospective studies is warranted.     

Three cases of hepatocellular carcinoma without distant metastasis effectively treated by sorafenib

Sorafenib is a novel, orally administered multi-kinase inhibitor that has recently been approved for the treatment of advanced hepatocellular carcinoma. We report three cases of hepatocellular carcinoma without distant metastasis effectively treated by sorafenib. Case 1 was a 71-year-old male with multiple hepatocellular carcinomas, Child-Pugh status A, and asthma. He received sorafenib 400 mg twice daily. The efficacy evaluated by the RECIST was partial response. Case 2 was a 75-year-old male with multiple hepatocellular carcinomas and Child-Pugh status A. He previously received surgical resection and transarterial chemoembolization. He received sorafenib 400 mg twice daily. The efficacy evaluated by the RECIST and modified RECIST was partial response and complete response, respectively. Case 3 was a 62-year-old male with multiple hepatocellular carcinomas and Child-Pugh status A. He previously received surgical resection, percutaneous radiofrequency ablation therapy and transarterial chemoembolization. He received sorafenib 400 mg twice daily. The efficacy evaluated by the RECIST was stable disease. The majority of adverse events were grade 1-2 stomatitis and hand-foot skin reaction. No patients discontinued the treatment because of adverse events. Sorafenib might be promising as an effective therapy for advanced hepatocellular carcinoma without distant metastasis.     

吉西他滨联合卡培他滨治疗耐药转移性乳腺癌的临床观察

目的探讨吉西他滨和卡培他滨联合化疗治疗蒽环类和(或)紫杉类耐药的转移性乳腺癌的近期疗效和不良反应。方法 2008年3月至2011年3月应用吉西他滨联合卡培他滨治疗转移性乳腺癌38例,每3周为1个周期,所有患者均评估毒性,对至少用过2个周期化疗的患者评估疗效。结果 CR 3例,PR 13例,SD 14例,PD 8例,有效率(CR+PR)为42.1%(16/38),临床获益率(CR+PR+SD)为78.9%(30/38)。主要不良反应为骨髓抑制、手足综合征、胃肠道反应。Ⅲ～Ⅳ度的骨髓抑制发生率低,手足综合征及消化道反应以Ⅰ～Ⅱ度为主。结论吉西他滨联合卡培他滨对蒽环类和(或)紫杉类耐药的转移性乳腺癌有较好的治疗效果,且不良反应可以耐受。     

Efficacy and Safety Profile of Combining Sorafenib with Chemotherapy in Patients with HER2-Negative Advanced Breast Cancer: A Meta-analysis

Purpose

The aim of the study was to evaluate the efficacy and safety of combining sorafenib with chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer.

Methods

MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, American Society for Clinical Oncology abstracts, and European Society for Medical Oncology abstracts were searched. Randomized clinical trials that compared the efficacy and safety of sorafenib plus chemotherapy in patients with HER2-negative advanced breast cancer with placebo plus chemotherapy were eligible. The endpoints were progression-free survival (PFS), overall survival (OS), time to progression (TTP), duration of response (DOR), overall response rate (ORR), clinical benefits, and adverse effects. The meta-analysis was performed using Review Manager 5.2.6 (The Nordic Cochrane Centre), and the fixed-effect model weighted by the Mantel-Haenszel method was used. When considerable heterogeneity was found (p<0.1), further analysis (subgroup analysis, sensitivity analysis, or random-effect model) was performed to identify the potential cause. The results are expressed as hazard ratios or risk ratios, with their corresponding 95% confidence intervals.

Results

The final analysis included four trials comprising 844 patients. The results revealed longer PFS and TTP, and higher ORR and clinical benefit rates in patients receiving sorafenib combined with chemotherapy compared to those receiving chemotherapy and placebo. OS and DOR were similar in the two groups. Meanwhile, the incidence of some adverse effects, including hand-foot skin reaction/hand-foot syndrome, diarrhea, rash, and hypertension, were significantly higher in the sorafenib arm.

Conclusion

Sorafenib combined with chemotherapy may prolong PFS and TTP. This treatment was associated with manageable toxicities, but frequent dose interruptions and reductions were required.     

Phase I/II study of sorafenib with anastrozole in patients with hormone receptor positive aromatase inhibitor resistant metastatic breast cancer

We evaluated the use of sorafenib to overcome resistance to aromatase inhibitors (AIs) in patients with metastatic breast cancer who had disease recurrence or progression while on AIs. We performed a multi-institution phase I/II study of sorafenib and anastrozole 1 mg daily in 35 postmenopausal females with hormone receptor positive metastatic breast cancer resistant to AIs. Primary objectives were to determine the dose of sorafenib in conjunction with anastrozole and the clinical benefit rate (CBR) (complete response [CR], partial response [PR], or stable disease [SD] ≥ 24 weeks). Secondary objectives were to determine toxicity and to evaluate if response was associated with change in number of circulating endothelial cells or circulating endothelial progenitor cells. Based on the phase I portion, sorafenib 400 mg twice daily was selected as the phase II dose. Among 35 patients, 7 had SD ≥ 24 weeks, 1 had PR ≥ 24 weeks, and 14 had progressive disease (PD) ≤ 24 weeks, corresponding to a CBR of 23%. The most common adverse events (all; Grade 3/4) were fatigue (66%; 17%), diarrhea (63%; 6%), nausea (60%; 9%), and hand-foot syndrome (57%; 34%). Dose reduction occurred in 77% of the patients and 31% came off study due to toxicity. The combination of sorafenib and anastrozole demonstrated a 23% CBR in patients with hormone receptor positive, AI-resistant metastatic breast cancer, which may be attributable to the restoration of sensitivity to AIs. Toxicities occurred frequently resulting in a high rate of discontinuation.     

Phase I targeted combination trial of sorafenib and erlotinib in patients with advanced solid tumors.

PURPOSE: Sorafenib and erlotinib are potent, orally administered receptor tyrosine kinase inhibitors with antiproliferative and antiangiogenic activities. Given their inhibitory target profile and efficacy as single agents, the combination of these drugs is of considerable interest in solid malignancies. This study aimed to determine the recommended phase II dose of this targeted combination, their toxicity profile, pharmacokinetic interaction, and preliminary clinical activities. EXPERIMENTAL DESIGN: Sorafenib was administered alone for a 1-week run-in period, and then both drugs were given together continuously, with every 28 days considered as a cycle. Three dose levels were assessed. RESULTS: Seventeen patients with advanced solid tumors received 75 cycles of treatment. The most frequent adverse events of all grades were constitutional and gastrointestinal in nature followed by electrolytes and dermatologic toxicities. Fatigue was the most common adverse event (17 patients; 100%) followed by diarrhea (15 patients; 88%), hypophosphatemia (13 patients; 76%), and acneiform rash (12 patients; 71%). These adverse events were predominantly mild to moderate. The recommended phase II dose of this combination was determined as 400 mg twice daily sorafenib and 150 mg daily erlotinib. Pharmacokinetic analysis revealed no significant effect of erlotinib on the pharmacokinetic profile of sorafenib. Among 15 evaluable patients, 3 (20%) achieved a confirmed partial response and 9 (60%) had stable disease as best response. CONCLUSIONS: Sorafenib and erlotinib are well tolerated and seem to have no pharmacokinetic interactions when administered in combination at their full single-agent recommended doses. This well tolerated combination resulted in promising activity that needs further validation in phase II studies.     

Toxicité cutanée induite par les thérapies ciblées anti-angiogéniques

Targeted angiogenesis inhibitors present a safety profile considered as acceptable. However, they are not without dermatological side effects. A majority of patients suffer from cutaneous toxicity, which can impact on their quality of life. These side effects appeared in the very first stages of development, particularly a very specific hand-foot skin reaction that can affect more than one in 3 patients using sorafenib. The dermatological toxicity that results from the suppression of the various signaling pathways by these new multitargeted inhibitors potentially provides information on the mechanisms governing epidermal or dermal homeostasis. We describe here the main dermatological adverse events resulting from sorafenib, sunitinib and bevacizumab. We include not only the complications described during the development phases but also those reported more recently following their more widespread use.     

索拉菲尼治疗肝癌常见不良反应及处理的研究进展

索拉菲尼是一种口服多激酶抑制剂。通过作用于Raf激酶直接抑制肿瘤细胞增殖,还可作用于血管内皮生长因子受体1,2,3（VEGFR-1, -2, -3）,以及血小板源生长因子受体-β（PDGFR-β）、受体酪氨酸激酶、抑制肿瘤新生血管生成。索拉菲尼通过抑制肿瘤细胞增殖和抗血管生成的双重作用,从而达到抗肿瘤的目的。已被多个国家批准作为首个系统治疗肝细胞肝癌的分子靶向药物。其常见不良反应包括皮肤反应、恶心、腹泻、体质量减轻、高血压等,影响了患者的长期使用依从性,进而影响治疗效果。正确地认识和管理索拉非尼的不良反应则有助于发挥索拉非尼的治疗作用,提高临床效果。本文从索拉菲尼靶向治疗的常见不良反应、发生机制及处理方法等方面进行综述。      

Results of a Phase I trial of sorafenib (BAY 43-9006) in combination with doxorubicin in patients with refractory solid tumors.

BACKGROUND: Sorafenib (BAY 43-9006), a novel, oral multi-kinase inhibitor, blocks serine/threonine and receptor tyrosine kinases in the tumor and vasculature. Sorafenib demonstrated single-agent activity in Phase I studies, and was tolerated and inhibited tumor growth in combination with doxorubicin in preclinical studies. This Phase I dose-escalation study determined the safety, pharmacokinetics and efficacy of sorafenib plus doxorubicin. PATIENTS AND METHODS: Thirty-four patients with refractory, solid tumors received doxorubicin 60 mg/m(2) on Day 1 of 3-week cycles, and oral sorafenib from Day 4 of Cycle 1 at 100, 200 or 400 mg bid. RESULTS: Common drug-related adverse events were neutropenia (56%), hand-foot skin reaction (44%), stomatitis (32%), and diarrhea (32%). The maximum tolerated dose was not reached. One patient with pleural mesothelioma achieved a partial response (modified WHO criteria) and remained on therapy for 39.7 weeks. Fifteen patients (48%) achieved stable disease for >/=12 weeks. Doxorubicin exposure increased moderately with sorafenib 400 mg bid. The pharmacokinetics of sorafenib and doxorubicinol were not affected. CONCLUSION: Sorafenib 400 mg bid plus doxorubicin 60 mg/m(2) was well tolerated. The increased doxorubicin exposure with sorafenib 400 mg bid did not result in significantly increased toxicity; low patient numbers make the clinical significance of this unclear. These promising efficacy results justify further clinical investigation.     

索拉非尼治疗国人晚期肝癌的临床观察

目的：观察索拉非尼治疗国人晚期肝细胞肝癌（ＨＣＣ）的有效性和安全性。方法：２０例晚期ＨＣＣ患者,口服索拉非尼单药治疗（４００ｍｇ,ｂｉｄ）,持续至疾病进展或出现不可耐受的不良反应,每６周按照ＲＥＣＩＳＴ标准（１.０版）进行疗效评价,按ＮＣＩ-ＣＴＣ（３.０版）评价毒性并动态监测甲胎蛋白（ＡＦＰ）的变化和随访生存情况。结果：在１９例可评价的患者中,获得ＳＤ１２例,ＰＤ７例,疾病控制率（ＤＣＲ）为６３.２％,中位肿瘤进展时间（ｍＴＴＰ）为３.８个月（９５％ＣＩ：２.５４～５.０６个月）,中位总生存期（ｍＯＳ）为６.０个月（９５％ＣＩ：３.９４～８.０６个月）,治疗前１２例ＡＦＰ高于正常,治疗后明显下降３例,稳定４例,升高５例。主要不良反应为手足皮肤反应、食欲下降和腹泻。结论：索拉非尼单药治疗晚期ＨＣＣ具有一定疗效,不良反应可以耐受,值得推广应用。     

多西紫杉醇联合希罗达治疗乳腺癌肺转移39例临床分析

目的 观察多西紫杉醇(紫杉特尔、Docetacel)联合希罗达治疗乳腺癌肺转移患者的临床疗效和不良反应,为临床治疗提供依据.方法 39例乳腺癌肺转移患者,用多西紫杉醇注射液75 mg/mz,第1天静脉滴注1小时,希罗达2 500 mg/m2,分早晚2次餐后半小时口服,第1-14天,21天为1个周期,连用4-6个周期.化疗前1天开始口服地塞米松8 mg,2次/天,连服3天,以防水钠潴留.每3周为1个周期,2个周期评价疗效.结果 39例患者完全缓解(CR)13例(33.3﹪),部分缓解(PR)14例(35.9﹪),总有效率(CR+PR)69.2﹪,稳定(SD)9例,进展(PD)3例.不良反应主要是骨髓抑制、胃肠道反应,对症治疗后均获得缓解,无化疗相关死亡.结论 多西紫杉醇联合希罗达治疗肺转移性乳腺癌有较好疗效,不良反应能耐受,是一种安全、有效的化疗方案.     

多西他赛（希存）联合希罗达治疗转移性乳腺癌的临床观察

目的探讨多西他赛联合希罗达治疗转移乳性腺癌的疗效及毒副反应。方法30例患者既往使用蒽环类治疗失败,采用多西他赛联合希罗达治疗,多西他赛75 mg/m2,静脉滴注,第1天;希罗达1000 mg/m2,分2次口服,第1~14天。21 d为1周期,2周期后评价疗效,有效者化疗4个周期以上。结果30例患者中,治疗后2例完全缓解(CR),18例部分缓解(PR),8例疾病稳定(SD),2例疾病进展(PD),有效率(CR PR)66.7%,肿瘤控制率(CR PR SD)93.4%。主要毒副反应为骨髓抑制,其中Ⅲ、Ⅳ级白细胞减少占13.3%。Ⅰ、Ⅱ级毒副反应为手足综合征,发生率为26.4%;恶心、呕吐发生率为60.0%;腹泻发生率为20.0%,患者均可耐受。结论多西他赛联合希罗达治疗转移性乳腺癌疗效好,毒副反应可耐受。