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.     

奥沙利铂联合羟基喜树碱治疗晚期胃癌临床分析

背景与目的体外及体内的临床研究显示,奥沙利铂(L-OHP)对多种肿瘤有显著抑制作用并与绝大多数抗癌药物具有相加或协同细胞毒作用.本文旨在观察L-OHP联合羟基喜树碱(HCPT)治疗晚期胃癌的近期疗效和患者耐受性,并与传统的化疗方案进行对比.方法采用非随机的分组方法将43例晚期胃癌患者分为L-OHP+HCPT方案组(治疗组)与Vp-16+CF+5-FU(ELF)方案组(对照组),其中男性28例,女性15例,中位年龄59岁,KPS评分≥60,观察两组的近期疗效和患者耐受性.结果治疗组24例有效率58.3%(14/24),对照组19例有效率42.1%(8/19).治疗组有效率高于对照组,两组差异有显著性(P<0.05).两组不良反应主要是骨髓抑制、恶心、呕吐、口腔炎、周围神经炎、静脉炎、脱发等,均在Ⅰ、Ⅱ度范围内.结论L-OHP联合HCPT方案治疗晚期胃癌疗效较好,不良反应可以耐受.     

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.     

Treatment of patients with myelodysplastic syndrome with amifostine

The efficacy and toxicity of amifostine (300 mg/m(2) three times a week for three consecutive weeks for a maximum of six courses) was evaluated in 12 patients with primary myelodysplastic syndromes. Dose escalation up to 400 mg/m(2) was allowed to patients who failed to respond. Hemoglobin concentration was increased > or = 1.5 g/dl in two (18%) of the 11 anemic patients. These two patients obtained transfusion independence for 20 weeks. Reticulocyte counts and ANC increased > or = 50% of baseline in four (44%) of the nine patients with reticulocytopenia and in three (25%) of the 12 neutropenic patients. Platelet count increased in three (50%) of the six patients with thrombocytopenia. Progenitor growth of CFU-GMs and BFU-Es improved in 8/12 patients. No major side effects were observed. In conclusion amifostine is well tolerated and can promote the growth of primitive hematopoietic progenitors and ameliorate the cytopenias in MDS patients.     

Outcome in patients with nonleukemic granulocytic sarcoma treated with chemotherapy with or without radiotherapy.

Granulocytic sarcoma (GS) is an extramedullary tumor composed of immature myeloid cells. The objectives of this study were to describe the frequency, presenting characteristics, and survival in patients with nonleukemic GS by conducting a review of all untreated patients presenting to the MD Anderson Cancer Center between January 1990 and June 2002. In all, 21 patients with nonleukemic GS, 1520 patients with acute myeloid leukemia (AML), and 402 patients with high-risk myelodysplastic syndrome (MDS) were identified. GS occurred in 1.4% of patients with AML, and 1.1% of patients with AML or high-risk MDSs. The median patient age was 57 years (range, 7-81). Among 20 patients with available cytogenetics in tissue and/or bone marrow, six had chromosome 8 abnormalities. The median follow-up of surviving patients is 12 months (range, 7-75). In all, 20 patients were treated. Patients were treated with AML-type chemotherapy (n=16), chemotherapy and radiotherapy (n=3), or radiotherapy alone (n=1). A total of 13 patients (65%) achieved complete remission and one patient (5%) achieved partial remission. The median overall survival was 20 months (range, 1-75), median overall failure-free survival was 12 months (range, 1-75). The median survival of patients with chromosome 8 abnormalities was 12 months compared with 40 months of those without (P=0.17). Novel therapies for patients with GS are required.     

Preoperative treatment with bevacizumab in combination with chemotherapy in patients with unresectable metastatic colorectal carcinoma

Purpose

This prospective observational study assessed the efficacy of bevacizumab in combination with chemotherapy as preoperative treatment to downsize tumours for radical resection in patients with unresectable metastatic colorectal cancer (mCRC).

Patients/methods

Patients with mCRC initially unresectable according to predefined criteria were included. Preoperative treatment consisted of bevacizumab (5 mg/kg) combined with oxaliplatin- or irinotecan-based chemotherapy, which was followed by surgery in patients showing clinical benefit. Resection rate was the primary endpoint. Response rate (RR) and clinical benefit of preoperative chemotherapy, and overall survival (OS) were secondary endpoints.

Results

A total of 120 eligible patients were included and received preoperative treatment. Chemotherapy was irinotecan-based in 73 (61 %) patients, oxaliplatin-based in 25 (21 %) and 22 (18 %) patients received more than one line. A RR of 30 % and a clinical benefit rate of 73 % were observed with preoperative chemotherapy. Metastatic resection was possible in 61 (51 %) patients. Median OS was 33 months (95 % CI 31–NA months) for patients undergoing surgery, and 15 months (95 % CI 11–25 months) in non-operated patients. Thirty-five patients experienced 59 postoperative complications (morbidity rate 57 %).

Conclusion

Preoperative bevacizumab-based chemotherapy offers a high surgical rescue rate in patients with initially unresectable mCRC.     

Correlation of immunophenotype with progression-free survival in patients with gastrointestinal stromal tumors treated with imatinib mesylate

BACKGROUND: The therapy for gastrointestinal stromal tumor (GIST) has been revolutionized by imatinib mesylate (IM). It is unknown whether the levels of KIT expression or the presence of CD34, smooth muscle actin (SMA), desmin, or S-100 protein predicts patient outcome from IM therapy. In the current study, the prognostic effects for KIT and other proteins (CD34, SMA, desmin, S-100) were analyzed in a series of GISTs in which protein expression was evaluated by immunohistochemical analysis (IHC). METHODS: The cases of 106 patients with GIST who were uniformly treated with IM at the study institution between December 15, 2000, and January 13, 2002 were evaluated retrospectively. The association between KIT intensity, CD34, desmin, SMA, S-100 protein, and progression-free survival (PFS) was studied. Kaplan-Meier analysis and the Cox proportional hazards regression model were used for statistical analysis. RESULTS: The majority of tumors arose from the stomach (37%), small intestine (35%), and colorectum (14%). KIT expression as determined by IHC was categorized as weak (10%), intermediate (32%), or strong (58%). Patient tumors expressed CD34 (75%), SMA (56%), desmin (1%), and S-100 protein (32%). Patients whose GIST had weak, intermediate, or strong KIT expression were found to have an 18-month PFS rate of 80%, 84%, and 69%, respectively (P = .30). The presence or absence of CD34, SMA, desmin, or S-100 protein did not appear to correlate with PFS after IM. CONCLUSIONS: Patients with the appropriate clinical presentation and KIT-positive GIST tumors appear to benefit from IM independent of the level of KIT or the expression of CD34, SMA, desmin, or S-100 protein by IHC.     

沙利度胺联合CAG方案治疗老年人急性髓系白血病效果观察

目的 评价沙利度胺联合CAG方案治疗老年急性髓系白血病（AML）患者的临床疗效及安全性.方法 对51例初治的老年AML患者进行前瞻性研究,采用简单随机分组法分为沙利度胺联合CAG方案治疗组26例、CAG方案单用对照组25例,评估临床疗效及患者不良反应.结果 诱导缓解治疗2个周期后,治疗组完全缓解（CR）率为61.5％（16/26）,对照组为48.0％（12/25）,两组差异无统计学意义（P=0.404）.治疗组1年CR率为53.8％（14/26）,对照组为24.0％（6/25）（P=0.045）;治疗组2年CR率为42.3％（11/26）,对照组为12.0％（3/25） （P=0.027）;治疗组1年及2年生存率分别为73.1％和46.1％,对照组分别为52.0％和24.0％;随访2年,治疗组中位生存时间为22个月,对照组为13个月,差异有统计学意义（P=0.018）.两组患者诱导死亡率及血液学不良反应发生率差异无统计学意义;但治疗组恶心、呕吐明显减轻,与对照组相比差异有统计学意义（P=0.025）.结论 沙利度胺联合CAG方案治疗老年AML患者,疗效理想,患者不良反应轻,值得进一步研究及临床应用.     

沙利度胺联合化疗治疗骨转移去势抵抗性前列腺癌的疗效观察

背景与目的:多西他赛联合泼尼松治疗可延长转移性去势抵抗性前列腺癌患者的生存期,血管生成抑制剂也可抑制肿瘤生长,联合治疗的疗效目前仍不明确.该研究旨在观察沙利度胺联合多西他赛和泼尼松治疗骨转移的去势抵抗性前列腺癌的近期临床疗效.方法:收集2008年12月—2015年6月南京军区福州总医院收治的骨转移去势抵抗性前列腺癌患者78例,其中40例作为对照组给予多西他赛和泼尼松方案化疗,38例作为观察组在对照组的基础上给予沙利度胺联合化疗,观察两组有效率、骨痛缓解率、前列腺特异性抗原(prostate specific antigen,PSA)无进展时间、无疾病进展时间及总生存时间,并评价不良反应.结果:观察组有效率为65.79%,PSA无进展时间为4.13个月,无疾病进展时间为4.25个月,骨痛缓解率为86.84%;对照组有效率为40.00%,PSA无进展时间为3.54个月,无疾病进展时间为3.75个月,骨痛缓解率为60.00%,观察组均高于对照组,差异有统计学意义(P<0.05).治疗后两组总生存时间、患者恶心呕吐及白细胞下降等不良反应发生率比较,差异无统计学意义(P>0.05).结论:沙利度胺联合化疗治疗骨转移的去势抵抗性前列腺癌近期临床效果满意,安全,不增加不良反应,具有较高的临床应用价值.     

尼妥珠单抗联合化疗治疗恶性胶质瘤

目的 评价尼妥珠单抗联合化疗治疗恶性胶质瘤的疗效及不良反应.方法 尼妥珠单抗200 mg/次,每周1次,连续8周后改为每2周1次;根据患者O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)蛋白表达状况和既往化疗效果,采用个体化的化疗方案.结果 14例恶性胶质瘤患者共接受尼妥珠单抗治疗122次,中位治疗7.5次(2～20次).联合的化疗方案中,替莫唑胺21 d方案10例,替莫唑胺5 d力案2例,替尼泊甙联合顺铂方案1例,替尼泊甙联合尼莫司汀方案1例.PR 3例(21.4%),SD 6例(42.9%),客观有效率为21.4%,疾病控制率(PR+SD)为64.3%.中位无进展生存期(PFS)为4个月(95%CI0.7～7.3),6个月的疾病无进展生存率为30.6%.主要的不良反应为Ⅰ～Ⅱ度的中性粒细胞下降(2例)、血小板下降(2例)、淋巴细胞下降(1例)、恶心呕吐(3例)和无症状的转氨,升高(1例).1例替尼泊甙联合顺铂方案化疗的患者发生Ⅳ度中性粒细胞下降和血小板下降.1例患者出现尼妥珠单抗治疗相关痤疮样皮疹.结论 尼妥珠单抗联合化疗治疗恶性胶质瘤有一定疗效,患者耐受性好,值得进一步扩大病例数开展临床研究.

Abstract：

Objective Nimotuzumab is a humanized monoclonal antibody targeted against epidermal growth factor receptor (EGFR). Recent clinical studies show that patients with malignant gliomas could benefit from nimotuzumab treatment. The aim of the present study was to evaluate the efficacy and side effects of nimotuzumab in combination with chemotherapy for patients with malignant gliomas. Methods The patients received 200 mg of nimotuzumab infusion intravenously over 60 minutes once weekly for the first eight weeks and then once every two weeks until unacceptable toxicity or tumor progression occurred.Individualized chemotherapy was administered based on O6-methylguanine-DNA methyltransferase (MGMT)expression and previous chemotherapy responses in combined with nimotuzumab. Results Fourteen patients received a total of 122 times of nimotuzumab ranging from 2 to 20 ( median 7.5 times ). Combined chemotherapy regimens included:continuous 21-day temozolomide ( 10 cases), standard 5-day temozolomide (2 cases), teniposide plus cisplatin ( 1 case), and teniposide plus nimustine ( 1 case). Partial response (PR) and stable disease (SD) were found in 3 patients (21.4%)and 6 patients (42.9%), respectively.Disease control rate ( PR + SD) was 64.3%. The median progression-free survival (PFS) was 4 months (95%CI:0.7-7.3) and PFS at 6 months was 30. 6%. The most common toxicities include grade Ⅰ -Ⅱ neutropenia (2 cases), thrombocytopenia ( 2 cases), lymphopenia ( 1 case), nausea and vomitting ( 3case) and asymptomatic transaminase increase ( 1 case). One patient developed grade Ⅳ neutropenia and thrombocytopenia. One patient developed nimotuzumab-related acneiform rash. Conclusions Nimotuzumab in combination with chemotherapy has moderate activity in patients with malignant gliomas and the toxicities are well tolerable, therefore, worth further investigation.     

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.     

Stage and treatment variation with age in postmenopausal women with breast cancer: compliance with guidelines

Breast cancer-specific mortality is static in older women despite having fallen in younger age groups, possibly due to lack of screening and differences in treatment. This study compared stage and treatment between two cohorts of postmenopausal women (55-69 vs >70 years) in a single cancer network over 6 months. A total of 378 patients were studied (>70: N=167, 55-69 years: N=210). Older women presented with more advanced disease (>70: metastatic/locally advanced 12%, 55-69 years: 3%, P<0.01). Those with operable cancer had a worse prognosis (Nottingham Prognostic Index (NPI) >70: median NPI 4.4, 55-69 years: 4.25, P<0.03). These stage differences were partially explained by higher screening rates in the younger cohort. Primary endocrine therapy was used in 42% of older patients compared with 3% in the younger group (P<0.001). Older women with cancers suitable for breast conservation were more likely to choose mastectomy (>70: 57.5% mastectomy rate vs 55-69 years: 20.6%, P<0.01). Nodal surgery was less frequent in older patients (>70: 6.7% no nodal surgery, 55-69 years: 0.5%, P<0.01) and was more likely to be inadequate (>70: 10.7% <4 nodes excised, 55-69 years: 3.4%, P<0.02). In summary, older women presented with more advanced breast cancer, than younger postmenopausal women and were treated less comprehensively.     

沙利度胺加联合化疗治疗恶性浆细胞疾病的疗效和不良反应

 目的 初步评价沙利度胺加联合化疗对恶性浆细胞疾病患者的疗效和毒副作用。方法17例多发性骨髓瘤和5例浆细胞白血病患者,采用沙利度胺联合VAD（T-VAD方案）或CED（T-CED方案）或MP（T-MP方案）治疗2～4疗程,评价其疗效和毒副作用。结果 21例可评价疗效的患者,6例（28.6 ％）获得完全缓解（CR）,10例（47.6 ％）获得部分缓解（PR）,总有效率（CR+PR）为76.2 ％,中位生存时间为48个月。所有患者共接受了86个疗程的治疗,最常见的不良反应为指端麻木感（40.9 ％）,便秘（40.9 ％）,嗜睡（36.4 ％）,水肿（27.3 ％）,未出现一例深静脉血栓（DVT）。结论 沙利度胺加联合化疗治疗恶性浆细胞疾病疗效好,毒副作用轻微,易于耐受。     

Mayo Clinic experience with 1123 adults with acute myeloid leukemia

Between 2004 and 2017, a total of 1123 adult patients (median age 65 years; 61% males) with newly diagnosed acute myeloid leukemia (AML), not including acute promyelocytic leukemia, were seen at the Mayo Clinic. Treatment included intensive (n = 766) or lower intensity (n = 144) chemotherapy or supportive care (n = 213), with respective median survivals of 22, 9, and 2 months (p < 0.01). Intensive chemotherapy resulted in complete remission (CR) and CR with incomplete count recovery (CRi) rates of 44 and 33%, respectively, with no difference in survival outcome between the two (p = 0.4). Allogeneic hematopoietic stem cell transplant (AHSCT) was documented in 259 patients and provided the best survival rate (median 55 months; p < 0.01). After a median follow-up of 13 months, 841 (75%) deaths were recorded. Multivariate analysis identified age >60 years (HR 2.2, 1.9–2.6), adverse karyotype (HR 2.9, 1.9–4.9), intermediate-risk karyotype (HR 1.6, 1.02–2.6), post-myeloproliferative neoplasm AML (HR 1.9, 1.5–2.4), and other secondary AML (HR 1.3 (1.1–1.6) as risk factors for shortened survival. These risk factors retained their significance after inclusion of FLT3/NPM1 mutational status in 392 informative cases: FLT3+NPM1− (HR 2.8, 1.4–5.6), FLT3+/NPM+ (HR 2.6 (1.3–5.2), and FLT3−NPM1− (HR 1.8, 1.0–3.0).Subject terms: Chemotherapy, Chemotherapy, Risk factors     

Association of age with survival in older patients with cutaneous melanoma treated with immune checkpoint inhibitors

IntroductionSeveral types of immune checkpoint inhibitors (ICIs) are approved to treat advanced melanoma, but their effectiveness has not been compared in older patients treated outside of a clinical trial. Moreover, evidence suggests that a patient's response to ICI therapy may vary by age and type of ICI. The purpose of this study was to compare survival by ICI type in older patients with melanoma and to investigate treatment effect modification by age.Materials and MethodsUsing the SEER-Medicare database, we identified patients with cutaneous melanoma (2012–2015) treated with an ICI (CTLA-4, PD-1, or combination CTLA-4 + PD-1 inhibitors). Cox proportional hazards regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for ICI types. We used an interaction term and stratified models to test for treatment effect modification by age.ResultsOf the 1435 patients included in our analysis, 790 (55.1%) received CTLA-4 inhibitors, 512 (35.7%) received PD-1 inhibitors, and 133 (9.3%) were treated with combination ICIs. Median survival ranged from 13.4 months (95%CI: 10.7–16.3) for CTLA-4 inhibitors to 23.5 months (95%CI: 16.2–30.0) for combination ICIs. In multivariable models, the risk of death was lower with PD-1 inhibitors compared to CTLA-4 inhibitors (HR = 0.78, 95%CI: 0.68–0.89). An age*ICI type interaction term was significant (p < 0.001), and survival gains were greater the older age group (≥80) compared to the younger group (65–79).DiscussionIn a population-based setting, we identified important differences in survival by ICI type in older patients with melanoma treated with ICIs, with prolonged survival associated with PD-1 inhibitors compared to CTLA-4 inhibitors.     

Prognostic score for patients with advanced melanoma treated with ipilimumab

BackgroundImmunotherapies like the cytotoxic T-lymphocyte antigen 4 inhibitor ipilimumab show durable clinical benefit in patients with advanced melanoma. Reliable prognostic markers and risk scores in the era of immunotherapy are still lacking.Patients and methodsWe collected characteristics and outcomes on 134 patients with metastatic melanoma treated with ipilimumab between 2011 and 2014 at a single centre. Cox regression including multivariable fractional polynomials was used to identify independent markers for overall survival (OS). Internal model validation was done using bootstrap procedures.ResultsAfter a median follow-up of 16.1 months the median OS was 7.1 months (95% confidence interval [CI], 6.5–9.8). Nineteen of 134 patients (14.2%) had tumour remissions, 16 partial and 3 complete; 75% had progressive disease. We identified three independent adverse factors for OS: elevated lactate dehydrogenase (LDH) (hazard ratio [HR] 1.03, 95% CI 1.02–1.04), Eastern Cooperative Oncology Group performance status >0 (HR 1.91, 95% CI 1.10–3.30), and number of organs involved (NOI) (HR 1.51, 95% CI 1.22–1.86). To build an easy-to-apply risk score, we dichotomized LDH (>upper limit of normal) and NOI (>2) to built 3 prognostic groups: favourable (no adverse factors, N = 17), intermediate (1 adverse factor, N = 38), and poor prognosis (≥2 adverse factors, N = 73). Respective 12 and 18-month OS for the risk groups were: 85% and 73% (favourable), 41% and 29% (intermediate), and 12% and 6% (poor) (p < 0.001).ConclusionWe propose a simple prognostic score for survival in patients with advanced melanoma treated with ipilimumab using readily available clinical parameters.     

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.     

尼莫斯汀联合顺铂持续灌注化疗治疗25例复发性胶质母细胞瘤

目的:评价尼莫司汀（ACNU）联合顺铂（CDDP）72h 持续灌注化疗治疗复发性胶质母细胞瘤的有效性及不良反应。方法:分析比较联合化疗组与替莫唑胺化疗组的疗效与不良反应。25例术后、放疗后复发的胶质母细胞瘤患者行ACNU 联合CDDP72h 持续静脉灌注化疗,36例胶质母细胞瘤患者单独接受替莫唑胺化疗。化疗后复查MRI 观察治疗效果,每周监测血常规及肝肾功能,及时处理化疗后的不良反应;随访患者生存时间。结果:联合化疗组肿瘤部分缓解（PR）14例（56%）;病情稳定（SD）8 例（32%）;肿瘤有进展（PD）3 例（12%）。 Ⅲ度以上白细胞降低的11例（44%）,Ⅲ度以上血小板降低的14例（56%）,经治疗均恢复,无治疗后死亡病例。联合化疗组短期疗效优于替莫唑胺组（P<0.05）,1 年生存率两组之间的差异无统计学意义（P>0.05）。 结论:ACNU 联合CDDP 72h 灌注化疗治疗复发性胶质母细胞瘤是一种比较有效的补救治疗手段,化疗后严重的骨髓抑制可经治疗得到缓解。