肿瘤相关炎性因子对曲妥珠单抗治疗HER2阳性转移性乳腺癌预后及疗效的影响

目的 研究肿瘤相关炎性因子(tumor associated inflammatory factor,TAIF)对曲妥珠单抗治疗人表皮生长因子受体2(HER2)阳性转移性乳腺癌(PMBC)预后及疗效的关系.方法 选取接受曲妥珠单抗方案治疗的HER2 PMBC患者89例纳入为试验组,选取同期接受健康体检的健康女性89例纳入为对照组,试验组所有患者均给予卡培他滨、吉西他滨联合曲妥珠单抗治疗,观察化疗前两组及试验组化疗前后的TNF-α、IL-1β、IL-6、IL-8水平,试验组的临床疗效,并对影响曲妥珠单抗治疗HER2 PMBC患者预后的因素进行多因素回归分析.结果治疗后,试验组的RR为40.45％,DCR为69.66％,1年内复发、转移率为79.78％.化疗前,试验组的TNF-α、IL-1β、IL-6、IL-8水平均明显高于对照组(P﹤0.01).试验组化疗前的TNF-α、IL-1β、IL-6、IL-8水平均明显高于化疗后(P﹤0.01).化疗前后,试验组1年内复发、转移患者的TNF-α、IL-1β、IL-6、IL-8水平均高于未复发、转移患者(P﹤0.05).年龄、身高、体重不是影响曲妥珠单抗治疗HER2 PMBC患者预后的危险因素(P﹥0.05);TNF-α、IL-1β、IL-6、IL-8是影响曲妥珠单抗治疗HER2 PMBC患者预后的危险因素(P﹤0.05).结论 TAIF可促进HER2 PMBC的进展、复发及转移,影响曲妥珠单抗治疗HER2 PMBC患者的疗效及预后.     

正念减压干预对宫颈癌放化疗患者自我感受负担、疼痛相关指标和炎性因子的影响

目的 探讨正念减压干预对宫颈癌放化疗患者自我感受负担、疼痛相关指标和炎性因子的影响.方法 将2018年5月至2019年3月收治的47例宫颈癌患者作为对照组,放化疗期间给予常规干预;将2019年4月至2020年2月收治的63例宫颈癌患者作为观察组,放化疗期间给予正念减压干预.干预前后,比较两组患者的血清疼痛相关指标[P物质、一氧化氮(NO)、前列腺素E2(PGE2)]和炎性因子[白细胞介素(IL)-6、IL-4、肿瘤坏死因子-α(TNF-α)]水平,采用自我感受负担量表(SPBS)评估两组患者的自我感受负担程度,采用癌症治疗功能评价系统普适量表(FACT-G)评估两组患者的生活质量.结果 干预后,两组患者SPBS量表各维度评分及总分均低于本组干预前,且观察组患者SPBS量表各维度评分及总分均低于对照组,差异均有统计学意义(P﹤0.05).干预后,两组患者血清P物质、NO、PGE2、TNF-α、IL-6和IL-4水平均低于本组干预前,且观察组患者血清P物质、NO、PGE2、TNF-α、IL-6和IL-4水平均低于对照组,差异均有统计学意义(P﹤0.05).干预后,两组患者FACT-G量表各维度评分和总分均高于本组干预前,且观察组患者FACT-G量表各维度评分和总分均高于对照组,差异均有统计学意义(P﹤0.05).结论 正念减压干预可以降低宫颈癌患者放化疗期间的自我感受负担程度,降低血清疼痛相关指标水平和炎性因子水平,改善生活质量.     

高效孕激素联合化疗治疗子宫内膜癌的疗效及对患者血清肿瘤标志物和炎性因子的影响

目的 探讨高效孕激素联合化疗治疗子宫内膜癌的疗效及对患者血清肿瘤标志物和炎性因子的影响.方法 96例子宫内膜癌患者均接受手术切除,根据术后化疗中是否使用高效孕激素,将其分为观察组(n=44)和对照组(n=52),对照组患者术后接受氟尿嘧啶+顺铂化疗,观察组患者在此基础上联合醋酸甲羟孕酮治疗.比较两组患者的临床疗效,治疗前后血清肿瘤标志物[包括糖类抗原125(CA125)、人附睾上皮分泌蛋白4(HE4)、甲壳质酶蛋白40(YKL-40)]和血清炎性因子[肿瘤坏死因子-α(TNF-α)、白细胞介素-4(IL-4)、白细胞介素-8(IL-8)]水平,以及不良反应发生情况.结果 观察组患者的总缓解率为75.00％,高于对照组患者的53.85％,临床获益率为93.18％,高于对照组患者的76.92％,差异均有统计学意义(P﹤0.05).治疗后,两组患者国际妇产科联盟(FIGO)分期变化情况比较,差异无统计学意义(P﹥0.05).治疗后,两组患者血清CA125、HE4、YKL-40水平均明显低于本组治疗前,且观察组患者血清CA125、HE4、YKL-40水平均明显低于对照组患者,差异均有统计学意义(P﹤0.01).治疗后,两组患者血清TNF-α、IL-4、IL-8水平均明显低于本组治疗前,且观察组患者血清TNF-α、IL-4、IL-8水平均明显低于对照组,差异均有统计学意义(P﹤0.01).观察组患者的不良反应总发生率为31.82％,低于对照组患者的36.54％,但差异无统计学意义(P﹥0.05).结论 醋酸甲羟孕酮联合化疗治疗子宫内膜癌患者的临床疗效较好,可进一步降低血清肿瘤标志物和炎性因子水平,安全性较高.     

异甘草酸镁联合XELOX方案对胃癌患者肝功能、炎性因子及血清肿瘤标志物的影响

目的:探讨异甘草酸镁联合XELOX方案对胃癌患者的肝功能、炎性因子和血清肿瘤标志物的影响。方法:选取2016年10月至2018年10月在我院消化内科住院治疗的胃癌患者80例为研究对象，按随机数字表法分为观察组及对照组（各40例）。两组均予以XELOX方案化疗，在此基础上，对照组加用还原型谷胱甘肽，观察组加用异甘草酸镁治疗。比较两组化疗前后的肝功能、炎性因子、血清肿瘤标志物水平。结果:治疗后，观察组ALT、AST、ALP、γ-GT、TBIL水平低于对照组(P＜0.05)［观察组TNF-α、IL-6、IL-8水平低于对照组(P＜0.05)［观察组CA19-9、CA125、CA72-4、CEA水平低于对照组(P＜0.05)［观察组ORR及DCR高于对照组(P＜0.05)。结论:异甘草酸镁能保护XELOX方案化疗胃癌患者肝功能，并能进一步降低其炎性因子及血清肿瘤标志物，发挥协同抗肿瘤效应。     

原发性结肠癌围手术期血清炎性因子水平的变化及其与患者术后疼痛控制效果的关系

目的 探讨原发性结肠癌围手术期血清炎性因子水平的变化及其与患者术后疼痛控制效果的关系.方法 采用ELISA法检测30例健康志愿者(健康组)和58例原发性结肠癌患者(疾病组)手术治疗前后的血清IL-6、IL-8和TNF-α水平,并分析其与患者疼痛控制程度的关系.结果 疾病组治疗前后的血清IL-6、IL-8和TNF-d水平和VAS评分均高于健康组;疾病组治疗后的血清IL-6、IL-8和TNF-α水平和VAS评分低于治疗前.VAS评分越高患者治疗前后的血清IL-6、IL-8和TNF-α水平均较高(P＜0.05).原发性结肠癌围术期血清IL-6、IL-8和TNF-oα水平与其VAS评分均呈正相关(γ =0.842,0.795,0.784,P＜0.05).结论 原发性结肠癌围手术期血清炎性因子水平较高,且与其VAS评分相关,炎症的控制有利于其疼痛的控制.     

多发性骨髓瘤患者血清VEGF和TNF-α及IL-6表达与沙利度胺联合化疗相关性研究

目的:探讨血清血管内皮生长因子(VEGF)、肿瘤坏死因子α(TNF-α)及白细胞介素-6(IL-6)在沙利度胺联合VAD方案化疗的多发性骨髓瘤(MM)患者中的表达及临床意义.方法:将46例MM患者随机分为T-VAD组(23例)和VAD组(23例),T-VAD组患者应用VAD方案同时连续口服沙利度胺200～250 mg/d联合化疗,共6个周期.VAD组患者行VAD方案化疗,共6个周期.用ELISA方法检测惠者治疗前后血清VEGF、TNF-α和IL-6水平.并以26例健康人作正常对照组.结果:VAD组和T-VAD组患者治疗前血清VEGF、TNF-α和IL-6水平较正常对照组均显著升高,两组差异无统计学意义(P＞0.05),与正常对照组比较差异有统计学意义,P＜0.01;治疗后两组患者血清VEGF、TNF-α和IL-6水平对照差异有统计学意义(P＜0.05),T-VAD组较VAD组下降更明显;两组治疗前后VEGF、TNF-α和IL-6水平差异均有统计学意义,P＜0.05.T-VAD组总有效率明显高于VAD组,P＜0.05.结论:MM患者血清VEGF、TNF-α和IL-6水平较正常人明显升高,T-VAD组治疗后总有效率明显高于VAD组,且T-VAD组较VAD组治疗后血清VEGF、TNF-α和IL-6水平下降更明显,对改善多发性骨髓瘤患者预后有重要作用.     

吉非替尼在表皮生长因子受体突变晚期非小细胞肺癌患者中的应用效果

目的 探讨吉非替尼在表皮生长因子受体（EGFR）突变晚期非小细胞肺癌（NSCLC）患者中的应用效果。方法 根据治疗方法的不同将90例EGFR突变NSCLC患者分为对照组和观察组,每组45例,对照组患者接受化疗,观察组患者在对照组的基础上联合吉非替尼治疗。比较两组患者的临床疗效、血清肿瘤标志物[神经元特异性烯醇化酶（NSE）、细胞角质蛋白19片段抗原21-1(CYFRA21-1)、癌胚抗原（CEA）]水平、免疫功能指标[免疫球蛋白G(IgG)、免疫球蛋白M(IgM)、免疫球蛋白A(IgA)]、炎性因子[白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)]水平及预后。结果 观察组患者的总有效率为68.89%,高于对照组患者的42.22%,差异有统计学意义（P<0.05）。治疗前,两组患者的NSE、CYFRA21-1、CEA、IgG、IgM、IgA、IL-6、TNF-α水平比较,差异均无统计学意义（P>0.05）。治疗后,两组患者的NSE、CYFRA21-1、CEA、IgG、IgM、IgA、IL-6、TNF-α水平均低于本组治疗前,观察组患者的NSE、CYFRA21-1、...     

多西紫杉醇联合GP化疗方案对晚期非小细胞肺癌患者炎性因子、免疫功能及临床症状的影响

目的 探讨多西紫杉醇联合吉西他滨+顺铂(GP)化疗方案对晚期非小细胞肺癌患者炎性因子、免疫功能及临床症状的影响.方法 回顾性分析40例晚期非小细胞肺癌患者的临床资料,所有患者均接受多西紫杉醇联合GP化疗方案,化疗2个周期后,比较化疗前后患者的血清炎性因子、免疫功能及临床症状.结果 化疗2个周期后,患者的血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、C-反应蛋白(CRP)浓度明显低于化疗前(P﹤0.01);CD3+、CD4+、CD4/CD8水平高于化疗前,CD8+水平低于化疗前,差异均有统计学意义(P﹤0.05);癌因性疲乏、局部疼痛及食欲不振评分均明显低于化疗前(P﹤0.01).结论 多西紫杉醇联合GP化疗方案能有效缓解晚期非小细胞肺癌患者的临床症状,可能与降低血清炎性因子水平、改善免疫功能等因素有关.     

骨髓瘤化疗合并感染患者血清炎性因子变化的临床意义

目的 探讨骨髓瘤化疗合并感染患者血清炎性因子水平变化.方法 选取规范化疗的骨髓瘤患者100例,其中合并感染19例作为感染组,未感染的81例作为非感染组.于同期再选取健康体检者32例做对比研究,即对照组.检测和记录感染组、非感染组、健康体检组研究对象血常规(WBC计数)、超敏C反应蛋白(hs-CRP)和血清炎性因子水平(IL-1β、IL-6、IL-8、TNF-α).比较3组研究对象IL-1β、IL-6、IL-8、TNF-α水平以及单一检测阳性率、联合检测阳性率,制作ROC曲线.结果 WBC计数水平,感染与非感染、健康体检组比较,差异无统计学意义(P＞0.05).hs-CRP,感染、非感染组高于健康体检组,差异有统计学意义(P＜0.05);感染组与非感染组比较,差异无统计学意义(P＞0.05).IL-1β、IL-6、IL-8、TNF-α水平,感染组高于非感染、健康体检组,差异均有统计学意义(P＜0.05).感染组IL-1β、IL-6、IL-8、TNF-α单一检测及联合检测和IL-6、TNF-α联合检测阳性率高于非感染者,差异有统计学意义(P＜0.05).ROC曲线下最大面积时水平作为临界值,IL-1β为5.76 ng/L,IL-6为4.85 ng/L,IL-8为55.78 ng/L,TNF-α为13.35 ng/L.结论 血清炎性因子水平变化可作为骨髓瘤化疗合并感染早期诊断指标,且有助于病情评价,尤其IL-6、TNF-α检测价值优于IL-1β、IL-8,二者联合检测优势更为突出.     

西妥昔单抗联合FOLFIRI方案对结肠癌患者炎性因子、免疫功能及预后的影响

目的 探讨西妥昔单抗联合伊立替康+亚叶酸钙+5-氟尿嘧啶(FOLFIRI)方案对结肠癌患者炎性因子、免疫功能及预后的影响。方法 根据化疗方案的不同将84例结肠癌患者分为对照组(n=41)和观察组(n=43),对照组患者给予FOLFIRI方案化疗,观察组患者给予西妥昔单抗联合FOLFIRI方案治疗。比较两组患者炎性因子[白细胞介素(IL)-4、IL-8、C反应蛋白(CRP)和肿瘤坏死因子-α(TNF-α)]水平、外周血T淋巴细胞亚群(CD3⁺、CD4⁺、CD8⁺、CD4⁺/CD8⁺)水平、不良反应及生存率。结果 治疗后,两组患者IL-4、IL-8、CRP、TNF-α水平均低于本组治疗前,观察组患者IL-4、IL-8、CRP、TNF-α水平均低于对照组,差异均有统计学意义(P﹤0.05)。治疗后,两组患者CD3⁺、CD4⁺水平和CD4⁺/CD8⁺均高于本组治疗前,CD8⁺水...     

Treatment with methylnaltrexone is associated with increased survival in patients with advanced cancer

BackgroundMethylnaltrexone (MNTX), a peripherally acting μ-opioid receptor (MOR) antagonist, is FDA-approved for treatment of opioid-induced constipation (OIC). Preclinical data suggest that MOR activation can play a role in cancer progression and can be a target for anticancer therapy.Patients and methodsPooled data from advanced end-stage cancer patients with OIC, despite laxatives, treated in two randomized (phase III and IV), placebo-controlled trials with MNTX were analyzed for overall survival (OS) in an unplanned post hoc analysis. MNTX or placebo was given subcutaneously during the double-blinded phase, which was followed by the open-label phase, allowing MNTX treatment irrespective of initial randomization.ResultsIn two randomized, controlled trials, 229 cancer patients were randomized to MNTX (117, 51%) or placebo (112, 49%). Distribution of patients' characteristics and major tumor types did not significantly differ between arms. Treatment with MNTX compared with placebo [76 days, 95% confidence interval (CI) 43–109 versus 56 days, 95% CI 43–69; P = 0.033] and response (laxation) to treatment compared with no response (118 days, 95% CI 59–177 versus 55 days, 95% CI 40–70; P < 0.001) had a longer median OS, despite 56 (50%) of 112 patients ultimately crossing over from placebo to MNTX. Multivariable analysis demonstrated that response to therapy [hazard ratio (HR) 0.47, 95% CI 0.29–0.76; P = 0.002) and albumin ≥3.5 (HR 0.46, 95% CI 0.30–0.69; P < 0.001) were independent prognostic factors for increased OS. Of interest, there was no difference in OS between MNTX and placebo in 134 patients with advanced illness other than cancer treated in these randomized studies (P = 0.88).ConclusionThis unplanned post hoc analysis of two randomized trials demonstrates that treatment with MNTX and, even more so, response to MNTX are associated with increased OS, which supports the preclinical hypothesis that MOR can play a role in cancer progression. Targeting MOR with MNTX warrants further investigation in cancer therapy.Clinical trials numberNCT00401362, NCT00672477.     

Improved survival in patients with breast rhabdoid tumors with multi-agent adjuvant chemotherapy combined with irradiation

Purpose  Malignant rhabdoid tumors (MRT) have poor prognoses. Breast MRT is extremely rare; only three cases have been documented, with a mean prognosis of 7 months. Multi-agent chemotherapy with mastectomy and irradiation, as used in this case, may extend survival in breast MRT. Patient and methods  A 68-year-old woman who underwent a standard mastectomy was diagnosed with breast MRT. Postoperatively she received six cycles of cyclophosphamide/methotrexate/5-fluorouracil followed by oral administration of doxifluridine and anastrozole, after which no metastasis was detected. About 8 months postoperative, magnetic resonance imaging revealed cervical bone metastasis, and local irradiation and nine doses of “basic chemotherapy” consisting of biweekly paclitaxel and anastrozole were administered. About 4 months later, multiple lung metastases were revealed, and four doses of “basic chemotherapy” with added pirarubicin hydrochloride were administered. Four months after that, multiple large liver metastases were discovered, and five doses of “basic chemotherapy” with added carboplatin were administered. Results  The 19-month survival period of our case was almost three times that of reported breast MRT patients. Conclusion  Multi-agent chemotherapy combined with irradiation may be associated with the relatively long survival of the present case.     

Compliance with guidelines and correlation with outcome in patients with advanced germ-cell tumours

PurposeTo evaluate prior compliance with guidelines in patients treated with salvage chemotherapy for advanced germ-cell tumours (GCT).Patients and methodsData concerning the initial management of patients requiring salvage chemotherapy for GCT at Institut Gustave Roussy between 2000 and 2010 were obtained and correlated with recommendations for treatment. Criteria of non-compliance were defined based on guidelines. Compliance with guidelines, predictive factors for non-compliance and the impact on outcome were analysed.ResultsAmong 82 patients treated in the salvage setting, guidelines to initial treatment were followed in only 41 cases (50%). The most common non-compliance criteria were non-adherence to the planned dose (16%), an inappropriate interval between first-line chemotherapy cycles (16%), the lack of post-chemotherapy surgery (16%) and a long interval to post-chemotherapy surgery (48%). Compliance with standard care was better in cancer centres than in other hospitals (private or public) (Odd Ratio (OR): 6.9, P = 0.001). A poor-risk status according to the International Germ Cell Cancer Collaborative Group (IGCCCG) was also predictive of compliance in univariate but not in multivariate analysis. No significant difference in outcome after salvage chemotherapy was observed. Patients relapsing after non-compliant first-line therapy tended to be more easily salvaged, which is consistent with the fact that their initial treatment was inadequate. Some of these relapses were therefore probably not due to true biologically refractory disease.ConclusionGuidelines for first-line treatment are adhered to in only half the patients requiring salvage chemotherapy. As the only predictive factor for non-compliance was the treating centre, centralisation of patients with GCT in well-trained hospitals should be recommended.     

Biomarkers associated with breast cancer are associated with obesity

Background: Obesity is linked to the development of postmenopausal breast cancer, and some studies indicate obesity predicts a worse prognosis for premenopausal women who develop the disease. It was our hypothesis that proteins associated with breast cancer would be associated with body mass index (BMI). Methods: We searched our database of women enrolled in breast health translational research trials for information on BMI and markers predictive of breast cancer (basic fibroblast growth factor (bFGF), prostate-specific antigen (PSA), human kallikrein (hK)2, and urinary plasminogen activator (uPA). Information on BMI and one or more nipple aspirate fluid (NAF) or serum biomarkers was available from 382 women. Results: In this data set, NAF and serum levels of PSA (nPSA and sPSA), and NAF levels hK2, bFGF and uPA were each associated with pre- and/or postmenopausal breast cancer. sPSA was inversely associated with BMI in both pre- (r = −.56, p = .001) and postmenopausal women (r = −.62, p = .0035) without breast cancer. This association was lost when controlling for plasma volume. In women without breast cancer, NAF bFGF (p = .07, premenopausal subjects) and NAF hK2 (p = .09, postmenopausal subjects) were borderline associated with BMI. In women with breast cancer, nPSA was inversely (r = −.53, p = .049) associated with BMI in premenopausal women and directly associated with BMI in postmenopausal women (r = .37, p = .017). nPSA trended higher in hormone sensitive cancers, especially those that expressed progesterone receptor (p = .059). Conclusions: sPSA was inversely associated with BMI in all pre- and postmenopausal women and specifically in pre- and postmenopausal women without breast cancer. NAF PSA was associated with BMI in pre- and postmenopausal women with breast cancer. Evaluating the change in PSA with changes in weight may provide clues regarding a subject's breast cancer risk.     

Costs associated with complications are lower with capecitabine than with 5‐fluorouracil in patients with colorectal cancer

BACKGROUND:

Capecitabine, an oral alternative to 5‐fluorouracil (5‐FU) in patients with colorectal cancer (CRC), has equal clinical efficacy and a favorable safety profile; however, its use may be limited because of unit cost concerns. In this study, the authors measured the cost of chemotherapy‐related complications during treatment with capecitabine‐ and 5‐FU–based regimens.

METHODS:

Patients with CRC who received at least 1 administration of capecitabine or 5‐FU during 2004 and 2005 were identified from the Thomson MarketScan research databases. Monthly frequency and cost for 23 complications were recorded. Logistic regression was used to predict complication probability. General linear models were used to predict monthly complication cost and total monthly expenditure.

RESULTS:

In total, 4973 patients with CRC met the inclusion criteria for this analysis. Although the most frequently observed complications were the same between capecitabine and 5‐FU (nausea and vomiting, infection, anemia, neutropenia, diarrhea), each was observed with greater frequency in 5‐FU–based regimens. The mean predicted monthly complication cost was significantly higher (by 136%) with 5‐FU monotherapy than with capecitabine monotherapy (difference, $601; 95% confidence interval [95% CI], $469‐$737). In addition, the mean predicted monthly complication cost for 5‐FU+oxaliplatin was higher than the cost with capecitabine plus oxaliplatin (difference, $1165; 95% CI, $892‐$1595). When acquisition, administration, and complication costs were taken into consideration, there were no significant differences in the total cost between capecitabine regimens and 5‐FU regimens.

CONCLUSIONS:

Capecitabine compared well with 5‐FU–based therapy in patients with CRC and was associated with lower complication rates and associated costs. Cancer 2009. © 2009 American Cancer Society.     

Adherence with surveillance schedule in patients with invasive melanoma

BackgroundSeven percent of patients develop melanoma recurrence after successful treatment, and 4–8% develop a second primary melanoma. This study aimed to assess how providing Survivorship Care Plans (SCPs) to patients may improve adherence to surveillance visits.MethodsAll patients treated for invasive melanoma at our institution between 8/1/2018-2/29/2020 were included in this retrospective chart review. SCPs were delivered in-person to patients and sent to primary care providers and dermatologists. Logistic regression was performed to assess influences on adherence.ResultsOf 142 patients, 73 (51.4%) received SCP regarding their follow-up care. Reception of SCP (p = 0.044) and shorter distance from clinic (p = 0.018) significantly improved rates of adherence. Seven patients developed melanoma recurrences, five were physician-detected. Three patients had primary site recurrence, six had lymph node recurrences, and three had distant recurrences. There were 5 second primaries, all physician-detected.ConclusionOur study is the first to investigate the impact of SCPs on patient adherence in melanoma survivors and the first to reveal a positive correlation between SCPs and adherence in any type of cancer. Melanoma survivors require close clinical follow-up, as demonstrated by our study finding that even with SCPs, most recurrences and all new primary melanomas were physician-detected.     

Temozolomide in combination with fotemustine in patients with metastatic melanoma

Purpose  Temozolomide and fotemustine are both active drugs for treating metastatic melanoma. The present study was designed to assess the efficacy and safety of combination therapy with temozolomide + fotemustine in patients with metastatic melanoma. Methods  Forty patients (median age 50.5 and 22 males) with pathologically confirmed, unresectable, AJCO stage IV melanoma were enrolled into the study. The primary endpoints were tumor response and safety. Patients received oral temozolomide 125 mg/m² on days 1–7 and intravenous fotemustine 80 mg/m² on day 3 every 3 weeks. Results  Fourteen (35%) patients achieved an objective response, including 3 (7.5%) complete and 11 (27.5%) partial responses. Median overall survival time was 6.7 months and 6-month survival rate was 57.4%. Myelosupression, particularly thrombocytopenia, was the primary toxicity. Conclusion  The regimen, temozolomide combined with fotemustine, is an active and moderately safe first-line chemotherapy regimen with acceptable and easily manageable toxicities in patients with metastatic melanoma.     

Varicella-Zoster Virus Prophylaxis with Low-Dose Acyclovir in Patients with Multiple Myeloma Treated with Bortezomib

BackgroundVaricella-zoster virus (VZV) reactivation is a common complication in patients with multiple myeloma (MM) treated with bortezomib, with an incidence rate of 10%-60%. The aim of our study was to analyze the effect of acyclovir prophylaxis in this patient population.Patients and MethodsWe studied 98 consecutive patients with relapsed MM treated with bortezomib. Bortezomib 1.3 mg/m² was given on days 1, 4, 8, and 11 of a 21-day cycle. At first, patients did not receive any VZV prophylaxis, but because of the high incidence of VZV reactivation, VZV prophylaxis with acyclovir was implemented subsequently.ResultsA total of 11 patients treated with bortezomib did not have any VZV prophylaxis, and 4 of these 11 patients (36%) developed VZV reactivation in the form of herpes zoster. No VZV reactivations were observed in the 32 patients who received acyclovir 400 mg 3 times daily or the 55 patients who received acyclovir in a dose reduced to 400 mg once daily during bortezomib treatment.ConclusionVaricellazoster virus reactivation is a common and serious adverse effect of bortezomib treatment. Acyclovir 400 mg once daily is sufficient to protect from VZV reactivation in patients with MM treated with bortezomib.     

A phase I study of extended dosing with lomeguatrib with temozolomide in patients with advanced melanoma

Lomeguatrib, an O⁶-methylguanine-DNA methyltransferase inactivator, was evaluated in an extended dosing regimen with temozolomide, designed according to pharmacodynamic data from previous studies. Patients with unresectable stage 3 or 4 cutaneous or unknown primary melanoma metastases were treated with lomeguatrib 40 mg, b.i.d. for 10 or 14 days and temozolomide 75–100 mg m⁻² on days 1–5. Drugs were administered orally with cycles repeated every 28 days, for up to six cycles. A total of 32 patients were recruited to the study. Lomeguatrib for 10 days with temozolomide 75 mg m⁻² was established as the optimal extended lomeguatrib dosing schedule, with haematological toxicity being dose limiting. There were two partial responses to treatment giving an overall response rate of 6.25%. Extending lomeguatrib administration beyond that of temozolomide requires a reduced dose of the latter agent. Only limited clinical activity was seen, suggesting no advantage for this regimen over conventional temozolomide administration in the treatment of melanoma.     

Biomarkers associated with breast cancer are associated with obesity

Background: Obesity is linked to the development of postmenopausal breast cancer, and some studies indicate obesity predicts a worse prognosis for premenopausal women who develop the disease. It was our hypothesis that proteins associated with breast cancer would be associated with body mass index (BMI). Methods: We searched our database of women enrolled in breast health translational research trials for information on BMI and markers predictive of breast cancer (basic fibroblast growth factor (bFGF), prostate-specific antigen (PSA), human kallikrein (hK)2, and urinary plasminogen activator (uPA). Information on BMI and one or more nipple aspirate fluid (NAF) or serum biomarkers was available from 382 women. Results: In this data set, NAF and serum levels of PSA (nPSA and sPSA), and NAF levels hK2, bFGF and uPA were each associated with pre- and/or postmenopausal breast cancer. sPSA was inversely associated with BMI in both pre- (r = −.56, p = .001) and postmenopausal women (r = −.62, p = .0035) without breast cancer. This association was lost when controlling for plasma volume. In women without breast cancer, NAF bFGF (p = .07, premenopausal subjects) and NAF hK2 (p = .09, postmenopausal subjects) were borderline associated with BMI. In women with breast cancer, nPSA was inversely (r = −.53, p = .049) associated with BMI in premenopausal women and directly associated with BMI in postmenopausal women (r = .37, p = .017). nPSA trended higher in hormone sensitive cancers, especially those that expressed progesterone receptor (p = .059). Conclusions: sPSA was inversely associated with BMI in all pre- and postmenopausal women and specifically in pre- and postmenopausal women without breast cancer. NAF PSA was associated with BMI in pre- and postmenopausal women with breast cancer. Evaluating the change in PSA with changes in weight may provide clues regarding a subject's breast cancer risk.