Evaluation of primary care physicians' competence in selective skin tumour triage after short versus long dermoscopy training: a randomized non-inferiority trial.

BACKGROUND: Although primary care physicians (PCPs) play a key role in skin cancer screening, their skills in detecting malignant tumours is suboptimal. OBJECTIVES: To determine whether a short dermoscopy e-learning course (4 h) in skin tumour diagnosis for PCPs is non-inferior to a long course (12 h) in selective triage of skin lesions. Secondly, to evaluate whether regular refresher training sessions are necessary to maintain the PCPs' skills in the medium term. METHODS: A randomized 2 × 2 factorial non-inferiority trial was conducted online over an 8-month period among 233 PCPs including 126 certified general practitioners, 94 PCPs in training, and 13 occupational physicians, all without prior advanced dermoscopy training. Participants were randomized 1:1:1:1 to receive short training and mandatory refreshers (n = 58), short training and optional refreshers (n = 59), long training and mandatory refreshers (n = 58), or long training and optional refreshers (n = 58). PCPs' skills were evaluated before training (T0), immediately after training (T1) to test the non-inferiority, and after 5 months (T2) to evaluate the impact of the refreshers. The primary endpoint was the difference in the change of score after short and long training. The non-inferiority margin was set at -28%. RESULTS: Among the 233 randomized participants, 216 (93%) completed T1 and 197 (84.5%) completed T2. For short versus long training, the primary endpoint was 1.392 (95% CI: 0.138; 2.645) in the per-protocol population (p < 0.001) and 1.016 (95% CI: -0.224; 2.256) in the modified intention-to-treat population (p < 0.001). After training, the type of refresher showed no impact on the score (p = 0.840). However, PCPs who completed all refreshers showed the best mean overall score at T2 (p < 0.001). CONCLUSIONS: These findings confirm that short dermoscopy e-learning is non-inferior in training PCPs to triage skin lesions compared to long training. After training, regular refreshers are important to maintain the PCPs' acquired skills over time.

Design of experiments in medical physics: Application to the AAA beam model validation.

PURPOSE: The purpose of this study is to evaluate the usefulness of the design of experiments in the analysis of multiparametric problems related to the quality assurance in radiotherapy. The main motivation is to use this statistical method to optimize the quality assurance processes in the validation of beam models. METHOD: Considering the Varian Eclipse system, eight parameters with several levels were selected: energy, MLC, depth, X, Y1 and Y2 jaw dimensions, wedge and wedge jaw. A Taguchi table was used to define 72 validation tests. Measurements were conducted in water using a CC04 on a TrueBeam STx, a TrueBeam Tx, a Trilogy and a 2300IX accelerator matched by the vendor. Dose was computed using the AAA algorithm. The same raw data was used for all accelerators during the beam modelling. RESULTS: The mean difference between computed and measured doses was 0.1±0.5% for all beams and all accelerators with a maximum difference of 2.4% (under the 3% tolerance level). For all beams, the measured doses were within 0.6% for all accelerators. The energy was found to be an influencing parameter but the deviations observed were smaller than 1% and not considered clinically significant. CONCLUSION: Designs of experiment can help define the optimal measurement set to validate a beam model. The proposed method can be used to identify the prognostic factors of dose accuracy. The beam models were validated for the 4 accelerators which were found dosimetrically equivalent even though the accelerator characteristics differ.

Interactions of grape tannins and wine polyphenols with a yeast protein extract, mannoproteins and ß-glucan.

At present, there is a great interest in enology for yeast derived products to replace aging on lees in winemaking or as an alternative for wine fining. These are yeast protein extracts (YPE), cell walls and mannoproteins. Our aim was to further understand the mechanisms that drive interactions between these components and red wine polyphenols. To this end, interactions between grape skin tannins or wine polyphenols or tannins and a YPE, a mannoprotein fraction and a ß-glucan were monitored by binding experiments, ITC and DLS. Depending on the tannin structure, a different affinity between the polyphenols and the YPE was observed, as well as differences in the stability of the aggregates. This was attributed to the mean degree of polymerization of tannins in the polyphenol fractions and to chemical changes that occur during winemaking. Much lower affinities were found between polyphenols and polysaccharides, with different behaviors between mannoproteins and ß-glucans.

Health-related quality of life in patients with melanoma expressed as utilities and disability weights.

BACKGROUND: Few studies about health-related quality of life (HRQoL) in patients with melanoma have expressed their results in terms of utilities or disability weights (DWs). Utilities are required for calculating quality-adjusted life years and therefore for cost-effectiveness analyses. DWs are useful to assess the burden of diseases through disability-adjusted life years. OBJECTIVES: To provide utilities and DWs regarding patients with melanoma. METHODS: The patients were classified into eight groups using four stages based on the 2009 American Joint Committee on Cancer stages, with each stage subdivided into treatment and remission phases. The EuroQoL Five Dimensions Five Levels (EQ-5D-5L) questionnaire was completed by the patients with melanoma to provide a mean utility for each group. In addition to this, the EuroQoL visual analogue scale (VAS) and a validated quality-of-life questionnaire dedicated to patients with melanoma [Functional Assessment of Cancer Therapy Melanoma (FACT-M)] were completed by the same patients in order to compare their results with the obtained utilities. DWs were obtained by calculating, for each patient, the difference between his/her utility and the corresponding sex- and age-specific population norm. RESULTS: A total of 395 questionnaire sets were completed. Utilities and DWs showed significant differences between follow-up groups. Treatment groups had similar utilities and DWs but these results were obtained during different treatment durations and therefore have different weights. The VAS and the FACT-M were found to be less sensitive. Nevertheless, the FACT-M identified some problems not found by the EQ-5D-5L questionnaire. CONCLUSIONS: The EQ-5D-5L questionnaire seems adequate to provide utilities and DWs in patients with melanoma. Lower HRQoL in female patients with melanoma is probably linked to lower HRQoL in the general population.

[Motivational interviewing use for promoting health behavior: an approach of doctor/patient relationship]. / L'entretien motivationnel dans la promotion des comportements de santé : une approche de la relation médecin/malade.

Many situations in common medical practice, especially in chronic diseases, require patients to be mobilized for health behavior decisions: for daily intake of an antihypertensive drug, performing a mammography for cancer screening, as well as adopting new diet habits in diabetes. Ability to initiate a health behavior depends on several parameters. Some of them are related to the patient, his personality, his illness and treatment's perception; others directly rely on the physician, his attitude and his communication style during the visit, independently of patient's level of resistance to change. Motivational interviewing (MI) is a communication technique, first developed for patients presenting a substance abuse disorder, to explore their ambivalence, overcome their resistances and give them the willingness of a better self-care. Its general principles and basic techniques can be applied by every practitioner and deserve to be better known, given that scientific literature provides evidence for generalizing it in a variety of medical conditions, in structured patient education programs as well as in usual follow-up, for which time is generally restricted. This article provides an overview of MI recent applications and argues for its diffusion in everyday medical practice.

Experimental determination of the effective point of measurement for cylindrical ionization chambers in 60Co gamma radiation.

The displacement effect of cylindrical ionization chambers is taken into account either by an effective point of measurement (EPOM) or, alternatively, by using a displacement perturbation factor. The dependence of these effects in water was examined as a function of the cavity radius using cylindrical chambers with different radii and a plane-parallel chamber, whose EPOM is well known. Depth-dose curves were measured in terms of absolute absorbed dose in water and evaluated according to the international protocol IAEA TRS-398 as well as the German protocol DIN 6800-2. As expected, evaluation of absorbed dose under reference conditions following both protocols agreed well within a standard uncertainty of 0.1%. However, values of absorbed dose at depths beyond the dose maximum showed deviations up to 0.3% and 0.5% for IAEA TRS-398 and DIN 6800-2, respectively. Values in the build-up and maximum region did not agree very well. Deviations of more than 1% were found for both protocols. It was concluded that the corrections recommended in both protocols are not fully appropriate. A procedure is suggested to measure the absorbed depth-dose distribution including the build-up region with an improved accuracy by means of cylindrical chambers.

Availability of digital dermoscopy in daily practice dramatically reduces the number of excised melanocytic lesions: results from an observational study.

BACKGROUND: Digital dermoscopy has been shown to permit an earlier detection of melanoma. However, few studies have investigated its added value in reducing unnecessary excisions in everyday clinical practice. OBJECTIVES: To compare, in daily practice, the efficiency of three dermoscopy methods: dermoscopy alone with little training, dermoscopy alone with adequate training and dermoscopy with adequate training and access to digital dermoscopy, and to confirm the safety of this latter approach. METHODS: Thirty-six dermatologists working without digital dermoscopy were divided into two groups according to their training in dermoscopy. The third group constituted of two dermatologists working in a pigmented lesion clinic with access to the digital dermoscopy technique and eight additional dermatologists working in the same dermatology department. These 46 dermatologists included all presumed melanocytic lesions excised over a period of 1 year. The primary endpoint was the melanoma/nonmelanoma ratio (M/NM-R); secondary endpoints were the ratio of 'problem' naevi to common naevi (PN/CN-R), specificity and sensitivity for the diagnosis of melanoma, in situ/invasive melanoma ratio, and the mean Breslow thickness. RESULTS: In total, 1865 excised lesions, including 231 melanomas, were included. In the digital dermoscopy availability group (DD-G) the M/NM-R was significantly better (1/2.43), as was the PN/CN-R (1/1.48) (P < 0.001 in both cases). The specificity was significantly higher in the DD-G and significantly higher for trained examiners as compared with examiners with little training. More that one-third of all melanomas discovered by digital dermoscopy were in situ, and the mean Breslow thickness was 0.32 mm for the invasive ones. CONCLUSIONS: The reduction of unnecessary excisions when using digital dermoscopy compared with dermoscopy alone in our study suggests that access to digital dermoscopy offers a better management of pigmented lesions in daily practice. The high number of early lesions diagnosed by this technique confirms that its use is safe.

[Unusual presentation of scurvy mimicking a neuroblastoma]. / Présentation inhabituelle d'un scorbut faisant craindre un neuroblastome.

Scurvy, a disease related to ascorbic acid deficiency, remains rare in industrial countries. Ascorbic acid is a vitamin that intervenes most notably in the synthesis of collagen and catecholamines. We report the case of a 2-year-old boy hospitalized in a pediatric oncology unit because of an unusual presentation of scurvy revealed by pain and a significant increase in urinary catecholamine levels, raising fear of a neuroblastoma.

A randomized phase II study comparing two schedules of the 21-day regimen of gemcitabine and carboplatin in advanced non-small cell lung cancer.

PURPOSE: Carboplatin area under the curve (AUC) 5 ml/min on day 1 with gemcitabine 1,250 mg/m(2) on day 1 and day 8 is a widely used regimen in advanced non-small cell lung cancer. Grade 3-4 thrombocytopenia and neutropenia are frequent. The aim of this study is to investigate whether toxicity of gemcitabine/carboplatin could be reduced by administering carboplatin on day 8 instead of day 1 without a decrease in response rate (RR). METHODS: Patients received gemcitabine 1,250 mg/m(2) on days 1 and 8, carboplatin AUC 5 on day 1 (arm A) or day 8 (arm B). Drugs were administered over a 21-day cycle. Toxicity and RR were evaluated weekly and every second cycle, respectively. RESULTS: 71 patients were enrolled into the study. We found 79% (95% CI 61-91%) grade 3-4 toxicity (neutropenia and thrombocytopenia) in arm A and 50% (95% CI 32-68%) in arm B; 66% grade 3-4 thrombocytopenia in arm A and 26% in arm B. We observed 30% grade 4 hematological toxicity in arm A and 3% in arm B. In arm A an overall RR of 20% (95% CI 7.7-38.6%) was seen, and 18.2% (95% CI 7-35.5%) in arm B. CONCLUSIONS: Although the study was prematurely closed, the current data are of interest. The schedule with carboplatin on day 8 is associated with substantially lower grade 3-4 neutropenia and thrombocytopenia with comparable dose intensity and RR.

A prognostic index for progression-free survival in malignant mesothelioma with application to the design of phase II trials: a combined analysis of 10 EORTC trials.

PURPOSE: For cytostatic agents or when the response assessment is difficult, adaptations to phase II designs may allow a better assessment of therapeutic activity: first by using the progression-free survival rate (PFSR) as primary end-point instead of the response rate, and second by considering progression-free survival (PFS) risk groups based on a prognostic index (PI). In mesothelioma, current treatments yield disappointingly poor results and there is a need to investigate new regimens. The purpose of this report is to provide a PI for PFS in mesothelioma and reference values for the PFSR. MATERIALS AND METHODS: Data on 523 patients included in 10 European Organisation for Research and Treatment of Cancer (EORTC) mesothelioma studies were analysed to identify prognostic factors using a multivariate Cox regression model. Subsequently, a PI and a nomogram for PFS were developed. The PFSRs at 3, 4, 5 and 6 months were estimated. RESULTS: A performance status>0, stage IV disease and mixed or sarcomatous histological type were indicators of a poor prognosis for PFS. From the PI, based on these three variables, four risk groups were defined. The median progression-free survival ranged from 5.3 to 2.1 months in these risk categories. The PFSRs at 3 months were 70.6%, 62.4%, 54.2% and 42.1% in the four categories, respectively. CONCLUSION: The PI allows dividing patients into homogeneous risk categories in which PFSRs can be calculated and used to design future phase II mesothelioma trials. Defining homogeneous categories of patients avoids dilution of results between groups and improves the assessment of therapeutic activity.

Validation of prognostic indices using the frailty model.

A major issue when proposing a new prognostic index is its generalisibility to daily clinical practice. Validation is therefore required. Most validation techniques assess whether "on average" the results obtained by the prognostic index in classifying patients in a new sample of patients are similar to the results obtained in the construction set. We introduce a new important aspect of the generalisibility of a prognostic index: the heterogeneity of the prognostic index risk group hazard ratios over different centers. If substantial variability between centers exists, the prognostic index may have no discriminatory capability in some of the centers. To model such heterogeneity, we use a frailty model including a random center effect and a random prognostic index by center interaction. Statistical inference is based on a Bayesian approach using a Laplacian approximation for the marginal posterior distribution of the variances of the random effects. We investigate different ways to summarize the information available from this marginal posterior distribution. Our approach is applied to a real bladder cancer database for which we demonstrate how to investigate and interpret heterogeneity in prognostic index effect over centers.

Reliability and limits of agreement of circumferential, water displacement, and optoelectronic volumetry in the measurement of upper limb lymphedema.

We conducted a reliability comparison study to determine the intrarater and inter-rater reliability and the limits of agreement of the volume estimated by circumferential measurements using the frustum sign method and the disk model method, by water displacement volumetry, and by infrared optoelectronic volumetry in the assessment of upper limb lymphedema. Thirty women with lymphedema following axillary lymph node dissection surgery for breast cancer surgery were enrolled. In each patient, the volumes of the upper limbs were estimated by three physical therapists using circumference measurements, water displacement and optoelectronic volumetry. One of the physical therapists performed each measure twice. Intraclass correlation coefficients (ICCs), relative differences, and limits of agreement were determined. Intrarater and interrater reliability ICCs ranged from 0.94 to 1. Intrarater relative differences were 1.9% for the disk model method, 3.2% for the frustum sign model method, 2.9% for water displacement volumetry, and 1.5% for optoelectronic volumetry. Intrarater reliability was always better than interrater, except for the optoelectronic method. Intrarater and interrater limits of agreement were calculated for each technique. The disk model method and optoelectronic volumetry had better reliability than the frustum sign method and water displacement volumetry, which is usually considered to be the gold standard. In terms of low-cost, simplicity, and reliability, we recommend the disk model method as the method of choice in clinical practice. Since intrarater reliability was always better than interrater reliability (except for optoelectronic volumetry), patients should therefore, ideally, always be evaluated by the same therapist. Additionally, the limits of agreement must be taken into account when determining the response of a patient to treatment.

Lessons to learn from EORTC study 08981: a feasibility study of induction chemoradiotherapy followed by surgical resection for stage IIIB non-small cell lung cancer.

The present EORTC phase II feasibility study in stage IIIB (T4-N3) NSCLC was conducted to investigate whether an induction regimen with concurrent chemoradiotherapy followed by surgery after restaging by re-mediastinoscopy and/or fluorodeoxyglucose-positron emission tomography (FDG-PET) was feasible in a multicenter setting. Unfortunately, the study closed prematurely because of poor accrual. The combination of more stringent selection criteria, the incorrect prevailing view of Ethical Boards that a tri-modality approach is too toxic, competing studies in the participating centers and the fact that patients with N3 disease could only be enrolled if a re-mediastinoscopy could be performed, underlie the low accrual. Although this study illustrates that the conduct of a tri-modality study across Europe appeared to be difficult at that time, the number of centers with highly qualified and experienced specialists involved in this kind of multi-modality approaches is rapidly increasing. Future initiatives should, therefore, certainly be encouraged. Minimally invasive procedures such as EUS and EBUS should preferably be used for up-front mediastinal staging, mediastinoscopy with or without EUS should preferably be reserved for restaging, and especially right-sided pneumonectomies should be avoided. Though evident, the feasibility to complete this kind of studies within a reasonable time period is still a condition sine qua non.

Is a patient's self-reported health-related quality of life a prognostic factor for survival in non-small-cell lung cancer patients? A multivariate analysis of prognostic factors of EORTC study 08975.

BACKGROUND: The aim of this prognostic factor analysis was to investigate if a patient's self-reported health-related quality of life (HRQOL) provided independent prognostic information for survival in non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Pretreatment HRQOL was measured in 391 advanced NSCLC patients using the EORTC QLQ-C30 and the EORTC Lung Cancer module (QLQ-LC13). The Cox proportional hazards regression model was used for both univariate and multivariate analyses of survival. In addition, a bootstrap validation technique was used to assess the stability of the outcomes. RESULTS: The final multivariate Cox regression model retained four parameters as independent prognostic factors for survival: male gender with a hazard ratio (HR) = 1.32 (95% CI 1.03-1.69; P = 0.03); performance status (0 to 1 versus 2) with HR = 1.63 (95% CI 1.04-2.54; P = 0.032); patient's self-reported score of pain with HR= 1.11 (95% CI 1.07-1.16; P < 0.001) and dysphagia with HR = 1.12 (95% CI 1.04-1.21; P = 0.003). A 10-point shift worse in the scale measuring pain and dysphagia translated into an 11% and 12% increased in the likelihood of death respectively. A risk group categorization was also developed. CONCLUSION: The results suggest that patients' self-reported HRQOL provide independent prognostic information for survival. This finding supports the collection of such data in routine clinical practice.

Docetaxel and cisplatin as induction chemotherapy in patients with pathologically-proven stage IIIA N2 non-small cell lung cancer: a phase II study of the European organization for research and treatment of cancer (EORTC 08984).

The objective of this phase II study was to document activity and toxicity of docetaxel and cisplatin as induction chemotherapy in patients with stage IIIA N2 non-small cell lung cancer (NSCLC) before definitive local treatment. Forty-six chemotherapy-nai ve patients (median age 60 years) were included. Treatment consisted of 3 cycles of docetaxel (85 mg/m2 on day 1), followed by cisplatin (40 mg/m2/day on days 1 and 2) every 21 days. Grade 3-4 leukopenia and neutropenia occurred in 45.7% and 65.2% of the patients, respectively. Among 8 cases of febrile neutropenia (17.4%), one (2.2%) resulted in early death. Common grade 3-4 non-haematological toxicities were nausea (17.4%) and vomiting (13%). Eighty-five percent of the patients received three courses; six stopped prematurely due to toxicity, one due to protocol violation. Response rate was the primary endpoint of this study. Considering eligible patients (n=40), 18 responses (1 complete and 17 partial responses) were observed (response rate 45%; 95% Confidence interval (CI): 29.3%-61.5%). In stage IIIA-N2 NSCLC patients, docetaxel-cisplatin could be administered and demonstrated manageable toxicity with modest efficacy.

Morbidity and mortality in the surgery arm of EORTC 08941 trial.

Controversial results of surgical treatment after induction chemotherapy, especially in relation to the extent of resection, have previously been reported. Mortality and morbidity were studied in the surgical arm of the European Organisation for Research and Treatment of Cancer (EORTC) 08941 trial. EORTC 08941 is a multicentre, prospective, randomised, phase-III trial of surgical resection versus radiotherapy in patients with proven stage IIIA-N2 nonsmall cell lung cancer after an objective response to platinum-based induction chemotherapy. Operative results in the 167 patients randomised in the surgical arm are presented within this study. Among these patients, one switched to the radiotherapy arm and 17 patients did not get any protocol treatment or information is not yet available. Radical resection with negative surgical margins was obtained in 74 patients (49.7%). In 61 patients (40.9%), a pathological down-staging to N0 or N1 was present. Operative 30-day mortality was 4.0%. Post-operative complications were mainly pneumonia, respiratory insufficiency, arrhythmias, air leak, cardiac decompensation, empyema and bronchopleural fistula. In total, 12 (8.1%) patients underwent re-operation due to positive margins, haemothorax, empyema and bronchopleural fistula. In conclusion, surgical resection after induction chemotherapy in the multicentre European Organisation for Research and Treatment of Cancer trial has yielded acceptable rates of morbidity and mortality.

Thyroid hormone signaling is highly heterogeneous during pre- and postnatal brain development.

We have generated transgenic reporter mice to analyze the spatio-temporal distribution of thyroid hormone signaling during mouse brain development. The reporter system, utilizing a chimeric yeast Gal4 DNA-binding domain-thyroid hormone alpha ligand-binding domain fusion protein to drive lacZ expression, revealed that thyroid hormone signaling starts in the midbrain roof several days before the onset of thyroid gland function, and that it remains highly heterogeneous in the central nervous system throughout pre- and postnatal development. We speculate that this heterogeneity might provide neural cells with positional information during development.

Overexpression of P70 S6 kinase protein is associated with increased risk of locoregional recurrence in node-negative premenopausal early breast cancer patients.

The RPS6KB1 gene is amplified and overexpressed in approximately 10% of breast carcinomas and has been found associated with poor prognosis. We studied the prognostic significance of P70 S6 kinase protein (PS6K) overexpression in a series of 452 node-negative premenopausal early-stage breast cancer patients (median follow-up: 10.8 years). Immunohistochemistry was used to assess PS6K expression in the primary tumour, which had previously been analysed for a panel of established prognostic factors in breast cancer. In a univariate analysis, PS6K overexpression was associated with worse distant disease-free survival as well as impaired locoregional control (HR 1.80, P 0.025 and HR 2.50, P 0.006, respectively). In a multivariate analysis including other prognostic factors, PS6K overexpression remained an independent predictor for poor locoregional control (RR 2.67, P 0.003). To our knowledge, P70 S6 kinase protein is the first oncogenic marker that has prognostic impact on locoregional control and therefore may have clinical implications in determining the local treatment strategy in early-stage breast cancer patients.

Carboplatin and paclitaxol (Taxol) as an induction regimen for patients with biopsy-proven stage IIIA N2 non-small cell lung cancer. an EORTC phase II study (EORTC 08958).

The aim of this study was to document the activity and toxicity of paclitaxel (Taxol)/carboplatin when used as induction chemotherapy in patients with stage IIIA N2 non-small cell lung cancer (NSCLC) prior to definitive local treatment within a large, ongoing comparative study (EORTC 08941). 52 eligible, consenting, chemotherapy-naïve patients with NSCLC, median age of 60 years, stage IIIA N2 disease and the ability to tolerate a pneumonectomy received paclitaxel 200 mg/m2 as a 3-h infusion followed by carboplatin at an area under the concentration curve (AUC) of 6 every 3 weeks for three courses. Most patients received three courses. No grade 3/4 anaemia or thrombocytopenia was documented. Over all of the cycles, 6% (3 patients) experienced grade 3 leucopenia while 63% (32/51 patients) experienced grade 3-4 neutropenia. There was 1 patient (2%) with febrile neutropenia, no early or toxic deaths and no hypersensitivity reactions. Severe non-haematological toxicity was uncommon, with the exception of grade 3 alopecia in 39%, lethargy in 8% and myalgia in 6%. Of the eligible patients (n=52), there was one complete response (CR) and 32 partial responses (PR), resulting in a response rate of 64% (95% Confidence Interval (CI) 49%-76%). Of the 15 eligible patients randomised to surgery after induction chemotherapy, 3 patients did not receive surgery and 2 patients (n=12) had no tumour in the mediastinal nodes (17%). Resections were considered complete in 2 of the 12. Median survival for all eligible patients (n=52) was 20.5 months (95% CI 16.1-31.2), with an estimated 1-year survival rate of 68.5% (95% CI 55.2-81.7). In patients with N2 stage IIIA NSCLC, paclitaxel/carboplatin is an active and very well-tolerated induction regimen.

Temozolomide in patients with advanced non-small cell lung cancer with and without brain metastases. a phase II study of the EORTC Lung Cancer Group (08965).

This study was performed to evaluate the activity of single-agent temozolomide in two groups of chemotherapy-naïve non-small cell lung cancer (NSCLC) patients, with (12 patients) and without (13 patients) brain metastases (BM). Patients in both groups were treated with temozolomide 200 mg/m(2)/day, administered orally for 5 consecutive days of a 28-day cycle. Treatment was continued for up to six cycles, disease progression or unacceptable toxicity. The median number of received cycles was only one in the group with and two in the group without BM, and early disease progression was the main reason for treatment discontinuation. Toxicity was moderate-in the group of patients with BM, the most frequently observed grade 3 or 4 side-effects included thrombocytopenia (17%), granulocytopenia (17%), lethargy (17%); other neurological (17%) and other genitourinary toxicity (17%). Patients without BM experienced anaemia (15%), thrombocytopenia (23%), nausea (15%) and lethargy (15%). This trial was designed according to Simon one-sample two-stage testing procedure and both groups of patients were assessed separately. No objective response was observed in either group and the study was closed after the first step of accrual with the conclusion of a lack of therapeutic activity of single-agent temozolomide in patients with stage IV NSCLC.