European Organization For The Research And Treatment Of Cancer Research Articles

Drug Insight: temozolomide as a treatment for malignant glioma—impact of a recent trial

Glioblastoma multiforme is the most common primary brain tumor in adults. Until recently, the standard of care consisted of maximal surgical resection followed by external beam radiotherapy. The role of adjuvant chemotherapy for newly diagnosed glioblastoma has been controversial; most of the numerous randomized phase III trials conducted over the past 40 years have failed to show a statistically significant and clinically meaningful survival advantage for patients randomized to the chemotherapy arm. Consequently, the choices of chemotherapeutics for patients with glioblastoma have been limited, and cytotoxic treatment regimens have usually included a nitrosourea. Temozolomide, a relatively new orally administered methylating agent, has demonstrable activity in glioma. A recent trial conducted under the auspices of the European Organization for the Research and Treatment of Cancer (EORTC) and National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) has defined a role for temozolomide in the initial management of glioblastoma. A companion correlative tumor-biology study has identified epigenetic silencing of the promoter of the gene that encodes MGMT (O6-methylguanine-DNA methyltransferase) in tumor specimens as a strong and independent prognostic factor for survival among patients with a newly diagnosed glioblastoma, as well as a predictor of survival benefit from chemoradiotherapy with temozolomide. This review briefly summarizes the development of temozolomide as a therapy for patients with malignant brain tumors, emphasizing recent trials that have established a new standard of care for patients with glioblastoma and speculating on how these advances might influence future therapeutic investigations for malignant primary brain tumors.

A meta-analysis of two randomised trials of early chemotherapy in asymptomatic metastatic colorectal cancer

This report constitutes a prospectively planned meta-analysis combining two almost identical trials undertaken in Australasia and Canada to study the effect of starting chemotherapy immediately in asymptomatic patients with metastatic colorectal cancer. Patients (n=168) were randomised to receive either immediate or delayed treatment (at onset of predefined symptoms). Australasian patients received either weekly 5-fluorouracil and leucovorin (500 and 20 mg m−2, respectively) (n=59) or the daily × 5 Mayo Clinic schedule (425 and 20 mg m−2, respectively) (n=42). Canadian patients were treated with the Mayo schedule (n=67). Otherwise, the two studies were almost identical in design and each used the European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 instrument for measuring quality of life (QoL). Treatment was continued until 6 months had elapsed or disease progression occurred. Low accrual led to trial suspension before the predetermined sample size for either study was reached. Median survival was not significantly better with immediate treatment (median 13.0 vs 11.0 months; hazard ratio, 1.15; 95% confidence interval (CI) 0.79–1.72; P=0.49). There was no statistically significant difference in progression-free survival (time from randomisation until first evidence of progression after chemotherapy, 10.2 vs 10.8 months; hazard ratio, 1.08; 95% CI 0.71–1.64; P=0.73). There was no difference in overall QoL or its individual domains between the two treatment strategies at baseline or at any subsequent time point. Early treatment of asymptomatic patients with metastatic colorectal cancer did not provide a survival benefit or improved QoL compared to withholding treatment until symptoms occurred.

QUALITY OF LIFE FOLLOWING SIMULTANEOUS PLACEMENT OF PENILE PROSTHESIS WITH RADICAL PROSTATECTOMY

The present study examined erectile functioning, frequency of sexual contact, psychological functioning, partner/marital satisfaction and overall quality of life (QOL) after immediate sexual rehabilitation for prostate cancer via simultaneous placement of a penile prosthesis at radical retropubic prostatectomy (RP). Questionnaire packets were sent to and received from 51 men who had undergone simultaneous implantation of a penile prosthesis at the time of RP (PP+) and from a comparison group of 47 men who undergone RP alone (PP-) matched by age and year of surgery. Questionnaires included the Erectile Dysfunction Inventory of Treatment Satisfaction, the Depression Anxiety Stress Scales, the Dyadic Adjustment Scale and a prostate specific European Organization for the Research and Treatment of Cancer (EORTC) QOL questionnaire. Further comparisons were performed for a PP- subgroup consisting of 15 patients who had undergone nerve sparing RP. Higher Erectile Dysfunction Inventory of Treatment Satisfaction, EORTC Sexual Functioning, EORTC Total scores and more frequent sexual contact were reported by the PP+ group compared with the PP- group. The PP+ group also had better outcomes that approached but did not reach statistical significance compared with the nerve sparing subgroup with regard to Depression Anxiety Stress Scales and EORTC Emotional Functioning scores. Men who chose simultaneous placement of a penile prosthesis with RP reported greater overall QOL, erectile function and more frequent sexual contact than a comparison group of men who underwent RP alone. Placement of penile prosthesis at the time of RP may be a desirable option for men with prostate cancer in whom a nerve sparing procedure may not be ideal. These results underscore the importance of sexual function for men undergoing prostate cancer treatment.

Treatment of myelodysplastic syndrome with isolated del(5q) including bands q31–q33 with a combination of all-trans-retinoic acid and tocopherol-α: a phase II study

All-trans-retinoic acid (ATRA) alone or in combination with cytokines and vitamins has been shown to stimulate erythropoiesis in low-risk myelodysplastic syndromes (MDS). We performed a phase II study on 29 patients with MDS and isolated del(5q) including bands q31-q33 to determine the efficacy and safety of ATRA in combination with tocopherol-alpha. All patients had low/intermediate-1 risk MDS according to the international prognostic scoring system. They received 45 mg/m(2) ATRA on days 1 to 90, and 90 mg/m(2) on days 91 to 180. Tocopherol dosage was 600 IU three times daily. Twenty-four patients completed dose level I, and 12 patients dose level II. Eighty-six percent of patients experienced side effects. Thirty discontinued the drug treatment due to such events as skin reactions, cheilitis, conjunctivitis, joint pain, creatinine increase, or CNS symptoms. One patient (3%) achieved a major erythroid response resulting in transfusion independence throughout the study. Four patients (14%) achieved a minor erythroid response with >50% reduction of transfusion needs. None of the participants had a cytogenetic response. There was no significant improvement in quality of life among responding patients as measured by the European Organization for the Research and Treatment of Cancer (EORTC) quality of life questionnaire. Based on these results, the combination of ATRA and tocopherol-alpha is not recommended for the treatment of del(5q) MDS.

Phase II Study of ET-743 in Advanced Soft Tissue Sarcomas: A European Organisation for the Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group Trial

This nonrandomized multicenter phase II study was performed to evaluate the activity and safety of Ecteinascidin (ET-743) administered at a dose of 1.5 mg/m(2) as a 24-hour continuous infusion every 3 weeks in patients with pretreated advanced soft tissue sarcoma. Patients with documented progressive advanced soft tissue sarcoma received ET-743 as second- or third-line chemotherapy. Antitumor activity was evaluated every 6 weeks until progression, excessive toxicity, or patient refusal. One hundred four patients from eight European institutions were included in the study (March 1999 to November 2000). A total of 410 cycles were administered in 99 assessable patients. Toxicity mainly involved reversible grade 3 to 4 asymptomatic elevation of transaminases in 40% of patients, and grade 3 to 4 neutropenia was observed in 52% of patients. There were eight partial responses (PR; objective regression rate, 8%), 45 no change (NC; > 6 months in 26% of patients), and 39 progressive disease. A progression arrest rate (PR + NC) of 56% was observed in leiomyosarcoma and 61% in synovialosarcoma. The median duration of the time to progression was 105 days, and the 6-month progression-free survival was 29%. The median duration of survival was 9.2 months. ET-743 seems to be a promising active agent in advanced soft tissue sarcoma, with no cumulative toxicities. The 6-months progression-free survival observed in advanced soft tissue sarcoma compares favorably with those obtained with other active drugs tested in second-line chemotherapy in previous European Organisation for the Research and Treatment of Cancer trials. The median overall survival was unusually long in these heavily pretreated patients mainly due to the high number of patients who benefit from the drug in terms of tumor control.

Initial English translation and validation of a symptom-specific quality of life (QOL) module for acute myeloid leukemia (AML)

8183 Background: QOL is becoming increasingly important in oncology and is usually measured using general cancer scales and symptom-specific scales. AML is an aggressive hematological tumor that affects primarily older adults and often responds poorly to standard treatment. Understanding QOL will assist in treatment decision-making, symptom palliation, and evaluation of new biologic agents. Yet there is no validated English-language symptom module for use in AML. Methods: In this pilot study, we set out to translate and perform English-language validation of an existing German symptom-specific module for AML designed by Schumacher and Kuchler for use with the European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 (Leukemia 1998; 12:586). Forward-backward translation of the 20-item module (7 subscales) was performed. Face and content validation of the English module were assessed by a panel of hematologists and QOL researchers. The module was then administered along with the QLQ-C30 to 14 English-speaking patients aged 60 or older with newly diagnosed AML at baseline and at 1 and 4 months. Semi-structured interviews were conducted with patients to assess clarity and comprehensiveness. Results: 10 men and 4 women with a mean age of 73 years completed the instruments on up to 3 occasions. Completion rates were 100%. The module was completed in a mean of 5 minutes (range 3–8). Item analysis indicated adequate scaling for all items. One question required minor rewording. No additional items were suggested by patients for inclusion. There were moderate correlations between global QOL on the QLQ-C30 and both general symptoms and diagnosis-specific symptoms in the symptom module. Pain subscales in the symptom module correlated well with the QLQ-C30 pain subscale. Conclusion: Administration of a symptom-specific QOL module is feasible in older patients with AML. The module has face and content validity, preliminary construct validity, and can be administered in a short time frame. Further testing is required to examine reliability, construct validity, and responsiveness. No significant financial relationships to disclose.

Initial English translation and validation of a symptom-specific quality of life (QOL) module for acute myeloid leukemia (AML)

8183 Background: QOL is becoming increasingly important in oncology and is usually measured using general cancer scales and symptom-specific scales. AML is an aggressive hematological tumor that affects primarily older adults and often responds poorly to standard treatment. Understanding QOL will assist in treatment decision-making, symptom palliation, and evaluation of new biologic agents. Yet there is no validated English-language symptom module for use in AML. Methods: In this pilot study, we set out to translate and perform English-language validation of an existing German symptom-specific module for AML designed by Schumacher and Kuchler for use with the European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 (Leukemia 1998; 12:586). Forward-backward translation of the 20-item module (7 subscales) was performed. Face and content validation of the English module were assessed by a panel of hematologists and QOL researchers. The module was then administered along with the QLQ-C30 to 14 English-speaking patients aged 60 or older with newly diagnosed AML at baseline and at 1 and 4 months. Semi-structured interviews were conducted with patients to assess clarity and comprehensiveness. Results: 10 men and 4 women with a mean age of 73 years completed the instruments on up to 3 occasions. Completion rates were 100%. The module was completed in a mean of 5 minutes (range 3–8). Item analysis indicated adequate scaling for all items. One question required minor rewording. No additional items were suggested by patients for inclusion. There were moderate correlations between global QOL on the QLQ-C30 and both general symptoms and diagnosis-specific symptoms in the symptom module. Pain subscales in the symptom module correlated well with the QLQ-C30 pain subscale. Conclusion: Administration of a symptom-specific QOL module is feasible in older patients with AML. The module has face and content validity, preliminary construct validity, and can be administered in a short time frame. Further testing is required to examine reliability, construct validity, and responsiveness. No significant financial relationships to disclose.

Hepatic arterial chemotherapy for colorectal cancer liver metastases: a review of advances in 2003.

During 2003, two new randomized trials comparing fluoropyrimidine-based hepatic arterial chemotherapy (HAC) with systemic chemotherapy were published. These new data will be reviewed in the context of previous trials and new observations of novel approaches involving HAC. The large Medical Research Council (MRC)/European Organization for the Research and Treatment of Cancer (EORTC) and the smaller Cancer and Leukaemia Group B (CALGB) trials reported conflicting conclusions. Lack of difference in response rates and survival outcomes was noted by the European trial groups whereas the contrary was reported by the US investigators, with statistically significant difference in response rates of 48% and 25% and median survival of 22.7 months and 19.8 months, respectively, being observed, favoring HAC. Early studies testing incorporation of irinotecan or oxaliplatin into HAC, either as additional systemic chemotherapy or as integral components of the HAC infusional regimen, confirmed feasibility, safety, and efficacy, with response rates between 30% and 60% being reported in some series. Other studies showed that combination with internal irradiation with lipiodol I-131 and biologic agents, eg, replication-selective adenovirus and cytokines, could be achieved with tolerable toxicity. Molecular prognostic factors that may help tailor treatment for individual patients were being investigated and low expression of thymidylate synthase (TS) and p21 was shown to correlate with better outcome, whereas patients with positive TS seemed to derive more benefit from HAC plus systemic chemotherapy than systemic chemotherapy alone. These studies confirmed that fluoropyrimidine-based HAC cannot be recommended routinely outside clinical trial as yet, but this treatment has its own merits and will continue to evolve with the availability of novel chemotherapeutic and biologic agents. Further studies into molecular prognostic factors will eventually define the role of HAC by selecting the right drug and the best route of administration for an individual patient.

Improved quality of life after long-term treatment with the bisphosphonate ibandronate in patients with metastatic bone disease due to breast cancer

Bone metastases occur in most women with advanced breast cancer and can lead to considerable morbidity and a rapid deterioration in the patient's quality of life. It was the aim of the present study to assess changes in quality of life and bone pain due to intravenous (i.v.) ibandronate, a potent third-generation bisphosphonate. In a phase III randomised, double-blind, placebo-controlled trial in patients with bone metastases due to breast cancer, 466 women were randomised to receive placebo, 2 mg ibandronate or 6 mg ibandronate for up to 96 weeks. Treatment was administered i.v. at 3- or 4-weekly intervals. Clinical endpoints included the incidence of adverse events, quality of life (assessed using the European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Scale – Core 30 questionnaire (QLQ-C30)), and bone pain (assessed on a 5-point scale from 0=none to 4=intolerable). Ibandronate was generally well tolerated. Compared with baseline measurements, the bone pain score was increased at the last assessment in both the placebo and 2 mg ibandronate groups, but was significantly reduced in the patients receiving 6 mg ibandronate (−0.28 ± 1.11, P<0.001). A significant improvement in quality of life was demonstrated for patients treated with ibandronate ( P<0.05) for all global health status. Overall, at the last assessment, the 6 mg ibandronate group showed significantly better functioning compared with placebo ( P=0.004), and had significantly better scores on the domains of physical, emotional, and social functioning, and in global health status ( P<0.05). Significant improvements in the symptoms of fatigue and pain were also observed in the 6 mg ibandronate group. I.v. ibandronate treatment leads to significant improvements in quality of life, and is an effective and well-tolerated palliative treatment in patients with bone metastases due to breast cancer.

Improved quality of life after long-term treatment with the bisphosphonate ibandronate in patients with metastatic bone disease due to breast cancer

<h2>Abstract</h2> Bone metastases occur in most women with advanced breast cancer and can lead to considerable morbidity and a rapid deterioration in the patient's quality of life. It was the aim of the present study to assess changes in quality of life and bone pain due to intravenous (i.v.) ibandronate, a potent third-generation bisphosphonate. In a phase III randomised, double-blind, placebo-controlled trial in patients with bone metastases due to breast cancer, 466 women were randomised to receive placebo, 2 mg ibandronate or 6 mg ibandronate for up to 96 weeks. Treatment was administered i.v. at 3- or 4-weekly intervals. Clinical endpoints included the incidence of adverse events, quality of life (assessed using the European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Scale – Core 30 questionnaire (QLQ-C30)), and bone pain (assessed on a 5-point scale from 0=none to 4=intolerable). Ibandronate was generally well tolerated. Compared with baseline measurements, the bone pain score was increased at the last assessment in both the placebo and 2 mg ibandronate groups, but was significantly reduced in the patients receiving 6 mg ibandronate (−0.28±1.11, <i>P</i><0.001). A significant improvement in quality of life was demonstrated for patients treated with ibandronate (<i>P</i><0.05) for all global health status. Overall, at the last assessment, the 6 mg ibandronate group showed significantly better functioning compared with placebo (<i>P</i>=0.004), and had significantly better scores on the domains of physical, emotional, and social functioning, and in global health status (<i>P</i><0.05). Significant improvements in the symptoms of fatigue and pain were also observed in the 6 mg ibandronate group. I.v. ibandronate treatment leads to significant improvements in quality of life, and is an effective and well-tolerated palliative treatment in patients with bone metastases due to breast cancer.

Does nutrition influence quality of life in cancer patients undergoing radiotherapy?

To investigate in cancer patients referred for radiotherapy (RT): (1) quality of life (QoL), nutritional status and nutrient intake, at the onset and at the end of RT; (2) whether individualised nutritional counselling, despite symptoms, was able to enhance nutrient intake over time and whether the latter influenced the patient's QoL; and (3) which symptoms may anticipate poorer QoL and/or reduced nutritional intake. One hundred and twenty-five patients with tumours of the head-neck/gastrointestinal tract (high-risk: HR), prostate, breast, lung, brain, gallbladder, uterus (low-risk: LR) were evaluated before and at the end of RT. Nutritional status was evaluated by Ottery's Subjective Global Assessment, nutritional intake by a 24-h recall food questionnaire and QoL by two instruments: EUROQOL and the European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30. Baseline malnutrition was prevalent in HR vs. LR (P=0.02); nutritional intake was associated with nutritional status (P=0.007); the latter did not change significantly during RT. In LR, baseline energy intake was higher than EER (P=0.001), and higher than HR' intake (P=0.002); the latter increased (P<0.03), in spite of symptom increase anew and/or in severity (P=0.0001). According to both instruments, QoL was always better in LR vs. HR (P=0.01); at the end of RT, QoL improvement in HR was correlated with increased nutritional intake (P=0.001), both remained stable in LR. Individualised nutritional counselling accounting for nutritional status and clinical condition, was able to improve nutritional intake and patients' QoL, despite self-reported symptoms.

Survival-weighted health profile for long-term survivors of acute myelogenous leukemia.

The objective of this study was to use survival-weighted psychometric scores (SWPS) to construct a 'health profile' for long-term survivors of acute myelogenous leukemia (AML). The study cohort included all patients who had been diagnosed and treated in our institution from 1985 to 1999 and achieved complete remission after standard chemotherapy (n = 259). One hundred and four patients were interviewed by the European Organization for the Research and Treatment of Cancer (EORTC)-QLQ-C30 questionnaire and the brief form of World Health Organization quality of life questionnaire (WHOQOL-BREF) to estimate the quality of life (QOL) function of the cohort. Forty-one patients underwent bone marrow transplantation (BMT) as consolidation or salvage therapy; 63 received chemotherapy alone. SWPS for every functioning domain and symptom item was obtained by direct integration of the mean QOL function with the survival function of the cohort. A Monte Carlo method was used to extrapolate the life-long SWPS beyond the follow-up limit. The mean scores of EORTC-QLQ-C30 and WHOQOL-BREF did not differ significantly between patients who received BMT or those who received chemotherapy only (p > 0.01). In mean SWPS, patients who received BMT had significantly (p < 0.01) better SWPS in all of the functioning domains and symptom items of EORTC-QLQ-C30 and all four domains of WHOQOL-BREF. However, when the life-long extrapolation of SWPS was made, these differences diminished in global health and several symptom items of EORTC-QLQ-C30 as well as in the social and environmental domains of WHOQOL-BREF. Patients' perspective on QOL may be domain-specific and may evolve over time. SWPS may be useful to evaluate the efficacy of different treatment strategies for AML. Confirmation of the relative merit of BMT vs. chemotherapy alone from prospective studies is needed.

Clinicopathologic reassessment of non-mycosis fungoides primary cutaneous lymphomas during 17 years.

New classification systems have recently been proposed for primary cutaneous lymphomas (PCLs). The aim of our study was to evaluate the applicability and significance of the new classification systems to the diagnosis and management of non-mycosis fungoides (non-MF) PCL. Immunohistochemical restaining, histological reclassification, and clinical follow-up of all new non-MF PCL cases during 17 consecutive years were performed. The histological reclassification was performed according to the Revised European-American Lymphoma (REAL) classification, except for lymphomatoid papulosis (Lyp), which was included as an indolent lymphoma, according to the European Organization for the Research and Treatment of Cancer (EORTC) classification. During the period 1983-99, 251 new PCL cases were seen, 213 (85%) of which were MF and Sézary syndrome (eight cases), and 38 (15%) of which were non-MF. Of the latter, 20 (53%) were B-cell lymphomas, including eight (40%) follicle center lymphoma, follicular (FCLF), eight (40%) marginal zone lymphoma (MZL), two (10%) diffuse large cell lymphoma, and two (10%) unclassifiable cases. Most or all of the lesions did not stain for CD10, CD43, and bcl-2 protein, and immunostaining for kappa and lambda immunoglobulin light chain restriction was much more useful diagnostically in MZL. Of the 18 primary non-MF cutaneous T-cell lymphomas, 13 (72%) were Lyp, all of which were type A, four (22%) were CD30+ anaplastic large cell lymphoma, and one (6%) was natural killer (NK)/T-cell lymphoma. Except for the NK/T-cell lymphoma, all the other non-MF PCLs had an indolent course. A minority of the routinely diagnosed PCLs are non-MF, equally divided between B- and T-cell lymphomas. The REAL classification is applicable to the majority, although it does not include entities such as Lyp; the clinical correlations are not as obvious because most of the non-MF PCLs tend to have a relatively indolent course.

Prospective analysis of quality of life after reversal of a defunctioning loop ileostomy.

OBJECTIVE: To measure changes in patients' quality of life following reversal of a defunctioning ileostomy in patients who had a curative anterior resection for rectal cancer. PATIENTS AND METHODS: Twenty consecutive patients undergoing reversal of a loop ileostomy following low anterior resection for primary rectal cancer participated. They answered three quality of life questionnaires: the European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-CR38, and the SF-36. Questionnaires were answered before reversal, on discharge home, and at 3 and 6 months postoperatively. RESULTS: Reversal of the defunctioning ileostomy resulted in significant improvements in global quality of life, physical function, social function, role-physical and energy-vitality scores. Post-operative diarrhoea and frequency improved over six months, but one third of patients had mild incontinence of faeces which did not improve with time. Emotional function, mental health, future perspective, perception of body image and general health perception did not change significantly after reversal. There was a significant negative correlation between defaecation-related problems, global quality of life and body image. CONCLUSION: Reversal of a defunctioning loop ileostomy improves most patients' overall quality of life. Therefore, once it is considered safe to reverse a stoma, an early operation may give the patient a longer time with an improved quality of life.

The emerging role of antifolates in the treatment of malignant pleural mesothelioma

Clinicians have long regarded malignant pleural mesothelioma as a chemoresistant neoplasm and as a result no standard chemotherapy regimen has emerged. Antifolates such as methotrexate are among the most active compounds in mesothelioma, albeit based only on phase II data. Recently two antifolate-based combinations with apparently higher efficacy than older regimens have emerged: the pemetrexed/cisplatin regimen and the raltitrexed/oxaliplatin regimen. In two phase I trials with pemetrexed combined with either cisplatin or carboplatin responses occurred in five of 11 and nine of 29 patients, respectively. In a phase I trial of raltitrexed/oxaliplatin, six of 17 patients (35%) with mesothelioma achieved a partial response. In a phase II trial of raltitrexed/oxaliplatin, 14 objective responses were confirmed in 72 patients (25%) with malignant pleural mesothelioma. Indeed, responses were seen in cisplatin-refractory patients. Based on the promising results from these combination trials, two large phase III studies have begun. The first study was a multicenter, multinational trial sponsored by Eli Lilly and Company, which randomized more than 430 patients with malignant pleural mesothelioma to cisplatin with or without pemetrexed. That trial completed enrollment in February 2001 and is the largest trial ever conducted in mesothelioma. The second trial is being conducted by the European Organization for the Research and Treatment of Cancer (EORTC) and compares cisplatin with or without raltitrexed with planned accrual of 240 patients. In both trials, survival is the main endpoint. These trials will help to define the role of these new antifolates in malignant pleural mesothelioma. Semin Oncol 29:77-81. Copyright © 2002 by W.B. Saunders Company.

The EORTC Boron Neutron Capture Therapy (BNCT) Group: achievements and future projects

Boron Neutron Capture Therapy (BNCT) is an experimental treatment modality that takes place in a nuclear research reactor. To progress from preclinical studies to patient treatment is a challenge requiring strict quality management and special solutions to licensing, liability, insurance, responsibility and logistics. The European Organisation for the Research and Treatment of Cancer (EORTC) BNCT group has started the first European clinical trial of BNCT for glioblastoma patients at the European High Flux Reactor (HFR) in Petten, The Netherlands, conducted by the Department of Radiotherapy of the University of Essen, Germany. A very strict quality management had to be installed following the European rules on safety and quality assurance for nuclear research reactors, for radioprotection, for radiotherapy and for clinical trials. The EORTC BNCT Group has created a virtual European-wide hospital to handle the complex management of patients treated with BNCT. New clinical trials are currently under development.

Quality of life and chronotherapy

The importance of evaluating patient's quality of life (QoL) in clinical practice and research is recognized clearly in oncology. In the advanced phase of disease such an evaluation represents an endpoint as important as survival. Quality of life is both a subjective and multidimensional concept evaluated mainly by validated questionnaires. In colorectal trials involving advanced stage disease the effects of different chemotherapy treatments on QoL were evaluated. Almost all the studies found no deterioration in QoL during chemotherapy. The European Organization for the Research and Treatment of Cancer (EORTC) Chronotherapy Study Group utilized three different approaches to assess QoL. The first centered on the stability of QoL during a 6mon treatment period in patients undergoing chronotherapy. The second centered on research of the biological and clinical determinants of QoL involving features of the circadian activity rhythm and patient survival and the relationship between QoL and patient performance status, response to therapy, and psychosocial variables as well as drug-induced toxicity. The third centered on the clinical effectiveness of psychological intervention on patients undergoing chronotherapy to improve psychosocial status during treatment. This papers reviews the results of EORTC Chronotherapy Group studies on QoL.

The impact of recurrent rectal cancer on quality of life

Aims: To determine, in patients operated upon for rectal cancer, the impact that tumour recurrence has on quality of life. Methods: Twenty-five patients, who had curative surgery for rectal cancer from 1992 to 1997, and who subsequently developed tumour recurrence, participated. Each patient was individually matched with two patients who also had rectal cancer surgery during the same period of time but were considered to be free of cancer. The patients were matched for age, gender, type of operation and socioeconomic status. They answered the European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 and CR38 quality of life questionnaires, as well as the SF36 II questionnaire, at least 1 year after surgery. Results: Patients with recurrent rectal cancer had significantly lower quality of life scores than cured patients in most dimensions, as measured by the three questionnaires. A significant difference was also seen in the global quality of life score on the QLQ-C30 (median scores 50 vs 75, z=4.015, P=0.0001). Conclusion: Recurrence of rectal cancer has a profound effect on quality of life, affecting most measurable dimensions. Treatment of recurrent cancer should not only be directed at the physical aspect of the disease, but also at its psychological and social aspects.

Establishing a therapeutic niche for tirapazamine

Tirapazamine is a new bioreductive agent that has exhibited cytotoxic activity against advanced tumours. Current studies are investigating how this agent can be used to its maximum potential. A combination of cisplatin and tirapazamine appears to be effective in chemotherapy-naive non-small cell lung cancer (NSCLC), leading to a greater response rate than that associated with cisplatin monotherapy. However, the combination has shown little promise in platinum-resistant tumours in phase II trials to date. Data from these studies were presented at the 9th National Cancer Institute (NCI) - European Organisation for the Research and Treatment of Cancer (EORTC) joint symposium [Amsterdam, The Netherlands; March 1996].

Quality of Life in Prostate Cancer: What Are the Issues and How Are They Measured?

Improvement of quality of life (QoL) has become a major endpoint in clinical trials of patients with prostate cancer. However, there still exist considerable methodological problems regarding the development of optimal instruments and methods for presenting the results. Within the European Organisation for the Research and Treatment of Cancer (EORTC) a core questionnaire is generally used for QoL evaluation, combined with a treatment- and disease-specific module. So far, no official EORTC prostate cancer module has been developed. Previous and ongoing trials in prostate cancer have addressed the following issues: for localised prostate cancer, micturition and sexuality, and for metastatic prostate cancer, bone pain, micturition, sexuality, vitality, hot flushes and gynaecomastia. The future challenge is to incorporate QoL results into the overall evaluation of treatment in combination with survival results and economical considerations.