An innovative symptom monitoring tool for people with advanced lung cancer: a pilot demonstration

Treatment for advanced lung cancer is not curative; therefore, the primary goals of its care are to maximize symptom management and minimize treatment toxicity. Increasingly, patient-reported symptoms and health-related quality of life (HRQL) outcomes have been accepted as important endpoints; several validated measures have gained wide acceptance in research, but their use in practice has been limited. Computer technology increasingly is used to reduce patient and administrative burden in conducting assessments to produce a real-time presentation of symptom and HRQL data.This paper describes a technology-based monitoring system developed for patients with advanced lung cancer who were starting chemotherapy. Among the 90 participants, compliance with the weekly symptom survey was 92%. Patient acceptability of the system was high, as evidenced by 30 patients who elected to complete an additional monitoring interval beyond the 12-week study period. Of patients who reported discussing their responses with a provider (95%), a majority (69%) stated that the questionnaire helped them to focus on issues to be discussed with their physicians. The system also was favorably reviewed by physicians, who indicated that the report helped them to compare patients' responses over time. Next steps will include a randomized trial to test the system's efficacy in improving symptom management.     

Measuring the symptom burden of lung cancer: the validity and utility of the lung cancer module of the M. D. Anderson Symptom Inventory

We conducted a study to establish the psychometric properties of a module of the M. D. Anderson Symptom Inventory (MDASI) developed specifically for patients with lung cancer (MDASI-LC). The MDASI measures 13 common "core" symptoms of cancer and its treatment. The MDASI-LC includes the 13 core MDASI symptom items and three lung cancer-specific items: coughing, constipation, and sore throat. MDASI-LC items were administered to three cohorts of patients with lung cancer undergoing either chemotherapy or chemoradiotherapy. Known-group validity and criterion (concurrent) validity of the MDASI-LC were evaluated using the Eastern Cooperative Oncology Group performance status and the 12-item Short-Form Health Survey. The internal consistency and test-retest reliability of the module were adequate, with Cronbach coefficient α-values of 0.83 or higher for all module items and subscales. The sensitivity of the MDASI-LC to changes in patient performance status (disease progression) and to continuing cancer treatment (effects of treatment) was established. Cognitive debriefing of a subset of participants provided evidence for content validity and indicated that the MDASI core items and three additional lung cancer-specific items were clear, relevant to patients, and easy to understand; only two patients suggested additional symptom items. As expected, the item "sore throat" was sensitive only for patients receiving chemoradiotherapy. The MDASI-LC is a valid, reliable, and sensitive symptom-assessment instrument whose use can enhance clinical studies of symptom status in patients with lung cancer and epidemiological and prevalence studies of symptom severity across various cancer types.     

Pemetrexed in the treatment of advanced non-small-cell lung cancer: a review of the clinical data

Pemetrexed is a novel multitargeting antimetabolite that has first-line and second-line activity against non-small cell lung cancer (NSCLC). Phase II studies have shown significant efficacy and a favorable toxicity profile of the combination of pemetrexed plus platinum as first-line therapy for NSCLC. Second-line activity against NSCLC was demonstrated in a phase III trial comparing single-agent pemetrexed with docetaxel; in that trial, survival was comparable between these agents but side effects were significantly less for patients who received pemetrexed. Pemetrexed is also an active agent against mesothelioma. A phase III trial comparing pemetrexed plus cisplatin with cisplatin alone showed for the first time a regimen that improves survival in this disease and led to FDA approval of pemetrexed in combination with cisplatin for mesothelioma. As a radiosensitizer, pemetrexed has been well-tolerated when given concurrent with chest radiation, and a phase I study is under way assessing its tolerability in combination with carboplatin in this setting. Pemetrexed is clearly a useful agent in the treatment of thoracic malignancies, and is worthy of further study in combination with other drugs having novel mechanisms of action.     

A brief symptom index for advanced lung cancer

BackgroundAdvanced lung cancer is often symptomatic; thus the goals of treatment include maintenance of function and palliation of symptoms. Symptom management requires accurate systematic symptom assessment. This study, which focused on lung cancer, is part of a larger study to obtain patient input that, in combination with previously obtained physician and nurse input, was used to develop symptom indexes for 11 advanced cancers.Participants and MethodsFifty patients with advanced lung cancer were recruited from National Comprehensive Cancer Network (NCCN) member institutions and community support agencies; 10 physician experts were recruited from NCCN institutions. Patients reported symptoms associated with their disease in open-ended format and then completed a checklist of symptoms, rating their 5 most important symptoms. Patient and provider ratings of symptom importance were tabulated to construct the NCCN-Functional Assessment of Cancer Therapy (FACT) Lung Symptom Index-17 (NFLSI-17). Patients also completed the Functional Assessment of Cancer Therapy-Lung (FACT-L), which was used to preliminarily validate the NFLSI-17.ResultsBased on combined patient, physician, and nurse input, the NFLSI-17 is composed of 17 priority symptoms, 11 that are disease related, 3 that are treatment related, and 3 that are related to general functional well-being (FWB). Data on 15 of 17 NFLSI-17 symptoms showed good internal consistency (alpha = 0.74) and strong association with the FACT-L total and most subscale scores (r = 0.42-0.92). Both the NFLSI-15 (F(2,47) = 4.46; P = .017) and the NFLSI-disease related subscale (DRS) (F(2,47) = 5.56; P = .007) significantly discriminated patients among performance status groups.ConclusionThe NFLSI-17 reflects the most important patient- and clinician-rated targets of chemotherapy for advanced lung cancer; further validation will follow.     

晚期NSCLC吉非替尼治疗失败后的再次治疗(病例报告及文献复习)

目的:对吉非替尼治疗失败后的晚期NSCLC患者再次使用吉非替尼治疗,分析其疗效及安全性。方法:复习1例吉非替尼治疗失败后的晚期NSCLC患者再次使用吉非替尼治疗及临床资料,结合相关文献探讨其临床特征、治疗及预后。结果:该患者首次使用吉非替尼约8月后耐药,停药5月后再次使用吉非替尼,1月后复查肺部CT提示肺部病灶明显缩小,2个月后再次失效,最终总生存期达21月,使用吉非替尼期间不良反应轻微。结论:曾使用吉非替尼有效的晚期NSCLC患者,再次使用吉非替尼仍有可能延长其生存时间且不良反应轻微。     

以单纯指骨转移为首发症状的肺癌2例并文献复习

目的探讨原发性肺癌以单纯指骨转移为首发症状的临床特点以及肺癌发生指骨转移的机理。方法对1991年至2007年间，见诸于有关文献报道的以单纯指骨转移为首发症状的原发性肺癌病人的文献资料进行综合性分析。结果在文献报道的以单纯指骨转移为首发症状的17例原发性肺癌的病人中，其转移病灶位于左手指骨者7例，右手指骨者9例，双手指骨者1例，指骨转移病灶的数量在两手之间的分布大致相等，除3例病人其转移病灶位于近节指骨外，其余病人的转移病灶均位于其末节指骨；有6例病人的患病手指既往曾有外伤史。结论传统的机械一解剖学说和种子一土壤学说的观点均不能解释原发性肺癌发生指骨转移的机理，故临床上如遇久治不愈的手指软组织炎症时，应想到是否有肿瘤细胞转移至此的可能性。     

Exercise and nutrition interventions in advanced lung cancer: a systematic review

In this systematic review, we sought to evaluate the effect of physical activity or nutrition interventions (or both) in adults with advanced non-small-cell lung cancer (nsclc).

Methods

A systematic search for relevant clinical trials was conducted in 6 electronic databases, by hand searching, and by contacting key investigators. No limits were placed on study language. Information about recruitment rates, protocol adherence, patient-reported and clinical outcome measures, and study conclusions was extracted. Methodologic quality and risk of bias in each study was assessed using validated tools.

Main Results

Six papers detailing five studies involving 203 participants met the inclusion criteria. Two of the studies were single-cohort physical activity studies (54 participants), and three were controlled nutrition studies (149 participants). All were conducted in an outpatient setting. None of the included studies combined physical activity with nutrition interventions.

Conclusions

Our systematic review suggests that exercise and nutrition interventions are not harmful and may have beneficial effects on unintentional weight loss, physical strength, and functional performance in patients with advanced nsclc. However, the observed improvements must be interpreted with caution, because findings were not consistent across the included studies. Moreover, the included studies were small and at significant risk of bias.More research is required to ascertain the optimal physical activity and nutrition interventions in advanced inoperable nsclc. Specifically, the potential benefits of combining physical activity with nutrition counselling have yet to be adequately explored in this population.     

Gemcitabine and carboplatin in advanced non small-cell lung cancer: a review

Both gemcitabine and carboplatin have demonstrated activity in advanced non small-cell lung cancer. The combination of gemcitabine and cisplatin has demonstrated equivalent or superior efficacy to other commonly used agents and two-drug combinations, and a recent Eastern Cooperative Oncology Group trial suggested that this regimen may have a slight advantage over other regimens in time to progression. The substitution of carboplatin for cisplatin offers the opportunity for a more well-tolerated regimen, and the combination of gemcitabine with carboplatin has now been studied in various clinical phase I and II trials. The administration of gemcitabine on a day-1-and-8 regimen with carboplatin appears to have a more favorable toxicity profile, especially with regard to platelet toxicity. Therefore, a number of ongoing trials, both phase II and phase III, are investigating the activity of this combination in locally advanced and metastatic non small-cell lung cancer. These trials will help define the role of this active and well-tolerated new regimen and, ultimately, its ability to be incorporated into multimodality therapy as well as with the new biologic agents for the treatment of non small-cell lung cancer.     

Erlotinib usage after prior treatment with gefitinib in advanced non-small cell lung cancer: A clinical perspective and review of published literature

Erlotinib and gefitinib are among the most widely researched, used and available molecularly targeted therapies for treatment of advanced non-small cell lung cancer (NSCLC). They are both tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR). In the past decade, there have been reports on clinical benefit from use of erlotinib after gefitinib failure in NSCLC patients. A review of published literature on this focussed topic is provided herein. Pooled analysis of published literature shows that majority of patients were female (60.6%), non-smokers (64.5%), had adenocarcinoma histology (88.3%) and were of East Asian ethnicity (92.3%). Presence of sensitizing EGFR mutation was detected in 48.4% of subjects. Disease control rates with prior gefitinib therapy and with subsequent erlotinib treatment were 79.4% and 45.4% respectively. Based upon our review, the most important predictive factor for clinical benefit from erlotinib identified was previous response to gefitinib. The exact explanations for the potential benefit from erlotinib use in this patient population is still not known and further studies are required to determine the role of molecular mechanisms especially those related to resistance to initial EGFR TKI therapy.     

Oxaliplatin doublets in non-small cell lung cancer: a literature review

Nowadays cisplatin doublets are considered the gold-standard treatment in advanced non-small cell lung cancer (NSCLC) patients, but are often associated to poor toxicity profile. In the last years different schedules have been developed in order to improve the tolerability of these regimens. Carboplatin is gradually replacing cisplatin in clinical practice as well as in clinical trials even if it is still unclear whether it has an equivalent efficacy compared to cisplatin. Oxaliplatin, the trans-l oxalato platinum compound, showed encouraging antineoplastic activity and favourable toxicity profile in NSCLC, but confirmatory randomized phase III trials are warranted. We performed a literature search in order to better understand the possible role of oxaliplatin-based combinations in advanced NSCLC treatment strategies.     

Taxane-platinum combinations in advanced non-small cell lung cancer: a review

Platinum-based chemotherapy is the treatment of choice for patients with non-small cell lung cancer (NSCLC). As a result of their single-agent activities and synergistic effects, taxane-platinum combinations are often used as first-line therapy for this disease. Four large, multicenter, randomized phase III clinical trials (the TAX 326 trial, the Southwest Oncology Group 9509 trial, the Italian Lung Cancer Project, and the Eastern Cooperative Oncology Group 1594 trial) have compared taxane-platinum combinations (docetaxel and paclitaxel) with other platinum combinations (vinorelbine and gemcitabine) in chemotherapy-na?ve patients with good performance status scores and advanced disease. The end points for these large randomized clinical trials were survival, response rate, adverse events, and quality of life (QOL). Of the taxane-platinum combinations tested, docetaxel-cisplatin was the only platinum combination to yield survival and response rates superior to another platinum combination. In adverse event terms, the taxane-platinum combination of paclitaxel-carboplatin demonstrated less grade 3 or 4 neutropenia and lower rates of febrile neutropenia than other taxane-platinum combinations but higher rates of irreversible grade 3 or 4 peripheral neuropathy than any of the other taxane-platinum combinations. Additional differences emerged when QOL data were evaluated. The docetaxel-platinum combination demonstrated broad QOL benefits for patients receiving this combination, and this benefit was not observed with the other platinum or taxane-platinum combinations. As our use of these taxane-platinum combinations expands, these differences in survival, response rate, adverse events, and QOL will permit us to better balance our treatment goals for all patients with all stages of NSCLC.     

Pemertrexed combined with cisplatin in the treatment of advanced non-small cell lung cancer: a case report and literature review

The aim of our study was to explore the value of second-line treatment for advanced non-small cell lung cancer (NSCLC). One patient with metastatic adenocarcinoma of NSCLC was given second-line treatment of pemertrexed/cisplatin. Follow-up was made to observe progression free survival (PFS) and survival time. She was given 4 cycles first-line treatment of recombinant human endostatin plus gemcitabine/cisplatin previously; the efficacy was CR and PFS was 10.2 months. After the 5th cycle treatment of pemetrexed/cisplatin, the efficacy of the primary tumor was CR, and bone metastases was stable. PFS was 6.6 months, and the patient has been survival for 22 months. Quality of life (QOL) of the patient was improved. When advanced NSCLC is recurrence or metastasis, starting second-line treatment of pemetrexed/cisplatin timely can prolong survival time and improve QOL.     

Staging practices of primary non-small-cell lung cancer: a literature review

Lung cancer is the most frequent cause of cancer deaths worldwide, and non-small-cell lung cancer (NSCLC) accounts for approximately 80% of all cases. Stage at diagnosis is the most important indicator of survival. Various non-invasive and invasive procedures are available for NSCLC staging. However, the precise indications for performing these procedures remain controversial. There is no evidence about the level of variability in practice of imaging and invasive procedures used for NSCLC staging. Their high costs contribute to the controversy about their use. We performed a literature search on the MEDLINE database to identify studies reporting practice of staging for a nonselected group of patients with NSCLC. Only seven studies enrolling between 185 and 2,071 patients reported NSCLC staging practices. These studies were reviewed to identify patterns in practice of staging work-up and consecutive treatment. Lack of detailed reporting limits the interpretation of the results. Based on our review, future investigations should be conducted to determine the extent of variation in patterns of physician practices of NSCLC staging and their impact on the treatment practice or patient survival.     

Management of malignant pleural effusion by suicide gene therapy in advanced stage lung cancer: a case series and literature review

Gene therapy can be defined as the transfer of genetic material into a cell for therapeutic purposes. Cytosine deaminase (CD) transferred into tumor cells by an adenoviral vector (Ad.CD), can convert the antifungal drug fluorocytosine (5-FC) to the antimetabolite 5-fluorouracil (5-FU), which kills not only the transfected tumor cells but also their neighbors by the so-called 'bystander effect'. After testing a protocol for Ad.CD transfer and lung tumor burden control in a Lewis mouse model, we used this technique in the management of lung cancer patients with malignant pleural effusion (MPE): two cases are presented investigating the possible enhancement of anticancer effect in both non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) by local activation of the pro-drug 5-FC. Results were discussed in parallel to a literature review on the topic. 5-FC and Ad.CD were administered intratumorally to Lewis mouse lung carcinoma and the effect was monitored by tumor size and electromicroscopy. Two patients with advanced stage lung cancer (1SCLC, 1NSCLC), which developed MPE during first-line treatment were administered 10(12) plaque-forming unit (pfu) Ad.CD by intrapleural instillation, in two doses (day1 and day7). Instillation was performed when the pleural fluid was 200?ml. In addition, they received 5-FC 500?mg four times daily for 14 days. Lung tumor regression and successful transfer of adenoviral particles were observed in treated animals. Patients presented complete regression of pleural effusion as monitored by computerized tomography scan. Neutrapenia and anemia were the most severe adverse effect presented (grade III/grade IV 100%). The increased toxicity followed by the intrapleural gene therapy indicates the augmentation of anticancer effect of transformed pro-drug 5-FC to active 5-FU. The obtained data indicate that intrapleural gene therapy may be a useful tool, adjunct to chemotherapy, in the management of MPE related to lung cancer.     

Oral ifosfamide-mesna: a clinical investigation in advanced non-small-cell lung cancer.

The purpose of this study was to evaluate the toxicity and response efficacy of fixed-dose oral ifosfamide (OI)-mesna (M) in advanced, non-small-cell lung cancer (NSCLC). OI was given in four different fractionated-dose treatment schedules with a total dose per cycle of either 3.0 g/m2, 6.0 g/m2, 7.5 g/m2 or 10 g/m2 (equivalent to a daily dose of either 750 mg, 1000 mg or 1250 mg.) M was given p.o. by drinking ampules. In the 64 patients (pts) included, a total of 305 treatment cycles were administered with no evidence of severe neurotoxicity. Twenty-two pts (37%) developed mild to moderate CNS toxicity. Neither myelosuppression, alopecia, gastrointestinal toxicity nor urotoxicity were clinical problems. On schedule 2 (6 g/m2), 3 of 14 evaluable pts (21%) had partial remissions (PR), and on schedule 3 (7.5 g/m2) 4 pts (25%) showed PRs. The median duration of response was 9 months (mts) for pts on schedule 2, and 8 mts for pts on schedule 3. We conclude that OIM can easily be tolerated in the same dose usually given intravenously (7.5 g/m2/mts), when patients at high risk for developing CNS toxicity have been previously excluded from therapy. In order to reduce CNS toxicity, it is suggested that the total dose per cycle should not exceed 7.5 g/m2 (1000 mg daily) within a fractionated-dose, 14-day treatment schedule. We further conclude that the tumor response efficacy of OIM in NSCLC is comparable to the one achieved by intravenously-administered IM, whereby the total monthly OI dose should not be less than 6.0 g/m2 (750 mg daily).     

Concurrent radiotherapy and chemotherapy for locally advanced non-small-cell cancer of the lung. Report of a clinical trial and review of the literature.

A prospective nonrandomized phase II study was begun in 1985 using concurrent split-course radiation and chemotherapy in the treatment of locally advanced non-small-cell cancer of the lung. Patients were treated with 3,000 cGy of radiation in 15 fractions to the chest, together with 100 mg/m2 cisplatin on day 1 and 1,000 mg/m2/day 5-fluorouracil infusion on days 1-4. The radiation and chemotherapy were then repeated after a 1-week break. Twenty-one patients were treated, with five patients having a complete response and nine patients having a partial response for an overall response rate of 67%. With a minimum of 24 months follow-up, five patients remain alive. Median survival for the entire group is 11.6 months. The toxicity of the treatment regimen was acceptable. These results do not differ significantly from survivals of similar patients treated with radiation alone, including a series from our own institution. The literature on concurrent chemotherapy and radiation is reviewed and possible future approaches to this tumor are discussed.     

Sequential, alternating, and maintenance/consolidation chemotherapy in advanced non-small cell lung cancer: a review of the literature

A platinum-based doublet with a third-generation agent (paclitaxel, vinorelbine, gemcitabine, docetaxel) represents the standard first-line treatment for advanced non-small cell lung cancer patients with good performance status (PS). Traditional chemotherapy provides response rates of 20%-40% and a median survival of 8-10 months. In an attempt to improve its outcome, alternative schedules have been proposed, namely sequential, alternating, and maintenance/consolidation therapy. Sequential chemotherapy with a platinum-based doublet followed by a single agent is feasible in patients with good PS; preliminary results from randomized phase III trials with combination chemotherapy as a comparator are promising, suggesting similar efficacy and a better toxicity profile for the sequential arm. The use of sequential single agents is an option for elderly and frail patients unsuitable for a platinum-based combination. Based on trials published so far, it is unlikely that an alternating chemotherapy strategy will be proven superior to standard chemotherapy in patients with good PS. However, sufficient evidence exists that it could be appropriate in the elderly or in unfit individuals. Consolidation/maintenance chemotherapy may provide additional benefit for patients achieving disease control after standard first-line chemotherapy. Better results are seen when maintenance consists of an agent that has proven active in the induction phase. Further evaluation of this strategy, as well as of consolidation/maintenance therapy with targeted agents, is warranted. In conclusion, these approaches may improve the outcome in selected patients with advanced non-small cell lung cancer, but further results from randomized trials are needed. In the meantime, sequential, alternating, and maintenance/consolidation therapy should still be considered investigational.     

Salvage therapy with vinorelbine in advanced non-small-cell lung cancer: a retrospective review of the Fox Chase Cancer Center experience and a review of the literature

BACKGROUND: Published phase III non-small-cell lung cancer (NSCLC) literature has demonstrated minimal activity for salvage vinorelbine (response rate [RR], 0.8% in 1 published study); however, our clinical experience has been discordant with such reports. PATIENTS AND METHODS: All patients with NSCLC who had received vinorelbine at Fox Chase Cancer Center from June 2002 to June 2005 were identified. Evaluable patients had biopsy-proven, measurable, recurrent or metastatic NSCLC, had full medical records and imaging available, and had received >or= 1 cycle of single-agent vinorelbine after first-line therapy. The primary endpoint was RR; secondary endpoints included safety, overall survival (OS), and time to progression. RESULTS: Of 52 patients, 39 were evaluable. Median age was 63 years and 59% of patients were women. The Eastern Cooperative Oncology Group performance status was 0 in 12.8% of patients, 1 in 53.8%, 2 in 25.6%, and 3 in 7.7%. Nearly 80% of patients underwent 2 lines of previnorelbine therapy; 38.4% underwent 3 lines, and 7.7% underwent 4 lines. Approximately, 28.2% had received previous epidermal growth factor receptor tyrosine kinase inhibitor therapy; 23% had brain metastases; and 84.6% had significant comorbidities. The most common dosing schedules were 25-30 mg/m(2) on days 1 and 8 every 3 weeks. The median number of vinorelbine cycles was 3. The partial RR was 7.7%; 25.6% had stable disease; 43.6% had disease progression, and 23.1% were not radiographically assessed for response (but were included in the OS analysis). Approximately, 20.5% required dose reductions, predominantly for hematologic toxicities; nonhematologic toxicities were generally mild, and there were no treatment-related deaths. Nearly 31% received subsequent therapy after vinorelbine. Median OS was 5 months (n = 39), median time to progression was 3 months (n = 30), 1-year OS was 25.6%, and 2-year OS was 7.7%. CONCLUSION: Salvage vinorelbine is active and well tolerated in patients with NSCLC. The RR exceeds that reported in the literature.     

阿帕替尼治疗晚期胃癌一例报告及文献复习

1病例资料 患者男性,52岁,2015年2月底因戒烟后出现恶心、厌食、乏力等不适,肝区疼痛并加重1d,于2015年4月3日至当地医院就诊.胃镜示:高位胃体小弯见1.8 cm×1.8 cm溃疡,表面覆白苔,周围黏膜隆起;胃窦前壁见0.8 cm×0.8 cm溃疡,表面覆白苔及血痂.诊断:多发性胃溃疡?浅表性胃炎伴隆起糜烂,十二指肠球炎.病理诊断:(胃体)低分化腺癌伴神经内分泌表达.免疫组化检测标志物:CAM5.2(+)、Villin(+)、P53(40％) CK20(-)、Syn(-/+)、Ki-67 (50％)、Muc-2(-)、CgA(+)、CD20(-)、Muc-5(-)、Cer-bB-2(-)、CDX2(+)、TopoⅡ(50％).2015年4月5日胸腹部CT:(1)右肺水平裂胸膜下小结节灶,性质待查;(2)胃窦占位?(3)肝脏占位、剑突前方软组织包块、小网膜腔及腹膜后淋巴结肿大并考虑转移灶可能性大.