The EORTC QOL Study Group is a multidisciplinary group which was founded in 1980 to promote collaboration between behavioural scientists and clinicians in addressing quality of life issues in oncology in Europe. Members of the group provide an advisory liaison service to the cooperative research groups of the EORTC when quality of life questions arise in their clinical trials. This raises conceptual, methodological and practical issues in study design and problems in data management and analysis. Individuals fuIfilling this function are supported by the group which meets twice a year to provide a forum for the exchange of ideas and experience in this field. The structure and function of the group has evolved over the years. Early sub-group activity spanned a range of conceptual issues in psychosocial oncology culminating in an important monograph in 1987. A major achievement of the group has been the development of a model and thence a measure for assessing QOL in clinical trials. International collaborative research under the leadership of Neil Aaronson has resulted in a 30-item cancerspecific questionnaire (EORTC QLQ-C30) which has proved practical, reliable, valid and sensitive to change in health status in international field testing. The group has now agreed guidelines to standardize the approach to the construction of complementary questionnaires or ‘modules’ to augment the QLQ-C30 to address additional diseaseor treatment-specific QOL issues. Several new projects consolidating the database on the QLQ-C30 and testing new modules are now underway. Quality of life assessment in small cell lung cancer: Results from three consecutive German multicentre randomized trials

Autologous stem cell transplantation with subsequent high dose therapy (HDT) is controversial in acute leukemia. We analysed the data of 46 patients (pts) who received autotransplants for acute leukemia in one center, 31 pts.with AML (acute myeloid leukemia), 15 pts with ALL (acute lymphoblastic leukemia). 41 pts (89%) were in CR 1,5 pts in CR 2 at the time of HDT. We reach the foilwing conclusions using a chemotherapy based conditioning regimen:

Zusammenfassung Die Sarkoidose ist eine granulomatöse Systemerkrankung, die sich bei über 90% der Patienten an der Lunge manifestiert, aber auch häufig extrapulmonale Organmanifestationen zeigt [8, 9]. Die Thrombozytopenie stellt eine seltene Komplikation der Sarkoidose dar, die in etwa 2% der Fälle gefunden wird [7]. Es wird eine Patientin mit einer Sarkoidose bei Multiorganbefall vorgestellt, bei der zudem eine Thrombo- und Leukozytopenie im Blutbild auffällig waren. Diagnostisch konnten eine Granulominfiltration des Knochenmarks sowie eine mäßiggradige Splenomegalie nachgewiesen werden, thrombozytäre Antikörper waren nicht zu objektivieren. Bei geringgradiger Knochenmarksinfiltration (ca. 5% Fläche des Markraums) muß ein sekundärer Hypersplenismus als wahrscheinlichste Ursache der Thrombo- und Leukozytopenie angesehen werden. Unter Stereoidtherapie fanden sich im Verlauf ein mäßiggradiger Anstieg der Thrombozyten- und Leukozytenwerte.

Chronic eosinophilic leukaemia has not yet been clearly defined, mainly due to the fact that it has not been conclusively shown as a monoclonal disease which should be separated from chronic myelogenous leukaemia, acute myelogenous leukaemia with eosinophilia (AML, FAB M4Eo), and the idiopathic hypereosinophilic syndrome.We report a patient with a white blood cell count of 17.6 × 109/l with 74% eosinophils, normal platelet count and haemoglobin. No blasts were seen in the peripheral blood and the percentage of blasts in the bone marrow was <3%. A diagnosis of chronic eosinophilic leukaemia was made. Chromosome analysis of a bone marrow aspirate disclosed a trisomy 15 together with loss of the Y chromosome. Moreover, FISH analysis on May‐Grünwald‐Giemsa‐stained peripheral blood smears demonstrated trisomy 15 in the eosinophils. 3 months after initial diagnosis the patient went into blast crisis and died. The blast cells exhibited trisomy 15 and loss of the Y chromosome in a complex, aberrant karyotype.In conclusion, the case shows that chronic eosinophilic leukaemia is a monoclonal, myeloproliferative disease with eosinophils as part of the malignant clone. Clinically, chronic eosinophilic leukaemia can be separated into a chronic phase and a blast crisis.

In a German multicenter trial, previously untreated patients with unresectable stages IIIA and IIIB non-small cell lung cancer were randomly assigned to receive either radiotherapy alone (arm A) or chemotherapy followed by radiotherapy (arm B). Chemotherapy in arm B consisted of ifosfamide 1,500 mg/m2 intravenously on days 1 to 5 and 29 to 33, and vindesine 3 mg/m2 intravenously on days 1 and 5 and 29 and 33. Radiotherapy started on day 1 in arm A and on day 56 in arm B. Single doses of 2 Gy were given 5 days a week for 3 weeks and after a 2-week interval for an additional 2 weeks. The total radiation dose was 50 Gy. Concurrent to radiotherapy, cisplatin was given as a radiosensitizer at a dose of 20 mg/m2 once a week. From July 1986 to March 1989, 85 patients were randomized, of whom 78 were evaluable. Main prognostic factors were well balanced. Of the patients receiving chemotherapy, 25% had a partial remission after two cycles, 46% showed no change, and 29% had progressive disease. After radiotherapy, response rates were 49% in arm A and 58% in arm B, including a 10% complete remission rate in both groups. After two thirds of the projected sample size had been included, an analysis of survival was performed and showed a statistically significant advantage for the treatment group including chemotherapy (P = .016). Median survival was 9.0 months versus 13.7 months and 2-year survival was 12% versus 24%, both in favor of the group receiving chemotherapy. These results caused premature discontinuation of patient accrual according to the study protocol and the recommendations of the Ethics Review Board of the Philipps-University Hospital. The results of this trial indicate that chemotherapy is able to prolong survival of patients with locally advanced unresectable non-small cell lung cancer and should be considered for treatment of these patients.

Conventional chemotherapy regimens produce 60%–70% complete remissions (CR) in patients with acute myeloid leukemia (AML). Long-term survival, however, is poor due to a high relapse rate. In most trials the long-term disease-free survival is in the range of 10%–20% [1–5]. Strategies to stabilize remission include maintenance therapy, early or late intensification or ablative forms of therapy with allogeneic or autologous bone marrow transplantation. While maintenance therapy gives a statistically significant but only small advantage in disease-free survival [1, 2], the role of intensification with conventional chemotherapy as double induction or late intensification has not been clearly established. Initial results show an increased number of disease-free survivors [6–8]. Increased long-term survival has been achieved with

The combination of radiotherapy and cytostatic drugs is of interest in the treatment of several solid tumors. In these preclinical investigations we tested whether ifosfamide and ACNU are able to enhance radiation effects. The experiments were performed by using the MTT assay. Two small cell and 2 non small cell lung cancer cell lines were involved. Ifosfamide, ACNU or both drugs together were tested in 6 different concentrations adjusted to the peak blood level. During the 1 hour drug incubation time, the cell lines were either irradiated with a single dose of 4 Gy or not. The main results were that ACNU possessed only little cytostatic activity in the cell lines under examination. In contrast, ifosfamide caused a dose related cytostatic activity in all cell lines. Concentrations of 26 μg/ml (NCC-SCLC H 82) or 10–12 μg/ml (3 other cell lines) were able to reduce the surviving cell fraction to less than 50% (IC50). While ACNU showed no clear outlined radiosensitizing properties, ifosfamide reinforced the radiation effects in 3 out of 4 cell lines indicating radiosensitizing properties of this drug. Synergistic effects of ifosfamide and ACNU have not been noticed. These preclinical investigations may constitute the basis for combined ifosfamide and irradiation therapy in future clinical trials.

The data of 766 patients participating in three German multicentre trials were analysed with regard to the relationship between baseline characteristics and prognosis in small cell lung cancer (SCLC). The central aim of this analysis has been to evaluate the role of gender as an independent prognostic factor in SCLC. The minimum follow-up period for the 652 male and 114 female patients was 36 months. Female patients were shown to have a higher complete remission rate (35% vs 25%), a superior median survival (ms) (12.1 months (mo) vs 9.8 mo), and a favourable 2-year survival rate (2ys) (19% vs 8%) to male ones. Various other prognostic factors have been proved to be significant, such as extent of disease, clinical performance status, and history of smoking, whereas weight loss prior to chemotherapy and age have been less important factors. We have been able to ascertain that women's responses were better than those of male patients independent of any other relevant prognostic variable. Furthermore, results were found to be even more advantageous for female patients with additional favourable prognostic parameters, i.e. for patients with limited disease (ms 15.2 mo vs 12.0 mo; 2ys 29% vs 9%) or with good performance status (ms 13.4 mo vs 10.4 mo; 2ys 24% vs 7%). A most remarkable observation was made in that the favourable prognostic effect of the female gender was restricted to patients aged less than 60 years (ms 13.3 mo vs 10.1 mo; 2ys 26% vs 5%), whereas for older women no advantages over men's results were established (ms 9.3 ml vs 9.1 mo; 2ys 8% vs 7%). A proportion of 32% of female patients with limited disease aged less than 60 years achieved a 3-year survival rate. We conclude (a) that sex constitutes a major prognostic factor in SCLC and is especially useful as a predictor for long-term survival, and (b) that the favourable prognostic value of the female sex is restricted to younger patients.

In three consecutive pilot studies the effect of recombinant human granulocyte/macrophage-colony-stimulating factor (rhGM-CSF) on haematopoetic recovery after chemotherapy in patients with small-cell lung cancer was investigated. In study I, 20 patients received AIO chemotherapy (A, Adriamycin 25 mg/m2 on days 1+2; I, ifosfamide 2 g/m2 on days 1–5; O, vincristine 2 mg on day 1) at 4-week intervals either with or without rhGM-CSF (250 μg/m2 sc) from day 8 until recovery of leucocytes. Neither the degree nor the duration of myelosuppression was markedly influenced by rhGM-CSF. Suggesting that these disappointing results were caused by the late onset of GM-CSF application, in the following study we shortened chemotherapy to 3 days and started with GM-CSF on day 4. The main objective of this study was to test whether the earlier administration of GM-CSF allowed treatment intervals to be reduced or the dose to be escalated. After 10 patients had received a starting dose of AIO (A, 50 mg/m2 on day 1; I, 2 g/m2 on days 1–3; 0,2 mg on day 1) alternating with cisplatin (90 mg/m2 on day 1) and etoposide (150 mg/m2 on days 1–3), the dose of ifosfamide and etoposide was escalated to 2.5 g/m2 on days 1–3 and 200 mg/m2 on days 1–3 in the next 10 patients. Treatment was given at 2-week intervals when leucocytes were > 3500/mm3 and thrombocytes were > 100 000 mm3 on day 14. At each dose level patients were randomized to receive either rhGM-CSF 250 μg/m2 s.c. on days 4–12 or no GM-CSF. In this study, rhGM-CSF markedly shortened the duration of leukopenia. Reinstitution of chemotherapy on day 15 was possible at dose level 1 in 1/4 patients without and in 3/4 patients with GM-CSF, and at dose level 2 in 0/5 patients without and in 5/5 patients with GM-CSF. However, the degree of myelosuppression was not improved by GMCSF. In a third study we tried to apply rhGM-CSF simultaneously with chemotherapy. After 3 patients had received GM-CSF starting on day 1 concurrent to AIO chemotherapy, we noticed an increase of myelosuppression with prolonged neutropenia and thrombocytopenia and stopped this investigation. Considering all patients included in these three consecutive pilot studies, there is no difference in response rates and survival between patients with and without rhGM-CSF treatment. Optimal scheduled rhGM-CSF application shortens the period of myelosuppression and allows reinstitution of chemotherapy at 2-week intervals. Whether these modifications are able to improve the overall treatment results, has to be determined in future clinical trials.

In order to define the maximum tolerance level of combined carboplatin/etoposide dosage, patients with extensive stage small-cell lung cancer (SCLC) were treated with a fixed dose of carboplatin (300 mg/m2 iv on day 1) and escalating doses of etoposide starting with 80 mg/m2 iv on days 1-3. Five patients were given this starting and every following dose level. The daily dose of etoposide was increased in increments of 20 mg/m2 iv until severe myelosuppression occurred in 3 of 5 patients. Leuko- or thrombocytopenia WHO grade 3 or 4 occurred in 0/5 of the patients at the dose levels of 80 and 100 mg/m2, in 1/4 of the patients at the level of 120 mg/m2, in 2/5 of the patients at a level of 140 mg/m2, and 3/5 patients at a level of 160 mg/m2. Thus, increase in dosage was stopped at an etoposide dose of 160 mg/m2. Other side effects were mild and consisted predominantly of nausea and vomiting in 14/25 of the patients. The overall response rate was 40% with a 12% complete remission rate, median survival was 9.3 months and median progression-free survival totalled 4.3 months. These results indicate that combined carboplatin/etoposide is a well tolerated regimen in extensive-stage SCLC, with response rates comparable to those of other standard protocols. Using treatment intervals of 4 weeks the recommended dose of etoposide in combination with 300 mg/m2 carboplatin was identified as 140 mg/m2 iv for 3 consecutive days.