Randomised, phase III trial of epoetin-β to treat chemotherapy-induced anaemia according to the EU regulation. Combined radiotherapy and chemotherapy with dibromodulcitol and CCNU in the postoperative treatment of malignant gliomas. Preoperative chemoradiotherapy versus preoperative radiotherapy in rectal cancer patients: assessment of acute toxicity and treatment compliance. Report of the 22921 randomised trial conducted by the EORTC Radiotherapy Group. Effects of counseling for late stage cancer patients. Feasibility of non-cisplatin-based induction chemotherapy and concurrent chemoradiotherapy in advanced head and neck cancer. A three-arm phase III randomised trial assessing, in patients with extensive-disease small-cell lung cancer, accelerated chemotherapy with support of haematological growth factor or oral antibiotics. Initial versus delayed accelerated hyperfractionated radiation therapy and concurrent chemotherapy in limited small-cell lung cancer: a randomized study. Effects of group CBT on the survival time of patients with metastatic breast cancer. Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer.
Erythropoietin-stimulating agents (ESAs) effectively decrease the transfusion requirements of patients with chemotherapy-induced anaemia (CIA). Recent studies indicate that ESAs increase mortality and accelerate tumour progression. The studies also identify a 1.6-fold increased risk of venous thromboembolism. The ESA labelling was thus revised in Europe and the United States in 2008. This is the first randomised, phase III trial evaluating the efficacy and safety of epoetin-β (EPO), an ESA, dosed in accordance with the revised labelling, which specifies that ESAs should be administered to CIA patients with a haemoglobin level of ≤ 10 g dl⁻¹ and that a sustained haemoglobin level of > 12 g dl⁻¹ should be avoided.
                A total of 186 CIA patients (8.0 g dl⁻¹ ≤ haemoglobin ≤ 10.0 g dl⁻¹) with lung or gynaecological cancer were randomised to receive EPO 36,000 IU or placebo weekly for 12 weeks.Results:The proportion of patients receiving transfusions or with haemoglobin < 8.0 g dl⁻¹ between week 5 and the end of the treatment period as the primary end point was significantly lower in the EPO group (n=89) than in the placebo group (n=92; 10.0% vs 56.4%, P < 0.001). The proportion receiving transfusions was significantly lower in the EPO group (4.5% vs 19.6%, P=0.002). Changes in quality of life were not different. No significant differences in adverse events - for example, the incidence of thromboembolic events was 1.1% for each group - or the 1-year overall survival were observed between groups.
                Weekly EPO administered according to the revised labelling approved by the European Medicines Agency is effective and well tolerated for CIA treatment. Further investigations are needed on the effect of ESAs on mortality. Within 4 weeks after definitive surgery, 91 patients with supratentorial glioblastomas and malignant astrocytomas were randomized to one of three treatment arms: Group 1 received radiotherapy alone; Group 2 received dibromodulcitol (DBD) during radiotherapy, and treatment was then continued with DBD; and Group 3 received DBD during radiotherapy, followed by combination chemotherapy of CCNU and DBD. No severe myelotoxicity occurred, but combined treatment with CCNU and DBD occasionally caused a transient myelosuppression. Statistical analysis of 84 evaluable patients showed a significantly longer survival period in those who received chemotherapy during and after irradiation. Median survival times in the three groups were 40, 57, and 60 weeks, respectively; the corresponding p value for Groups 2 and 3 was 0.025 and 0.0015. The ratio of patients surviving over 18 and 24 months was highest in Group 3. This study suggests that the administration of DBD during irradiation might have been the main factor in improving survival times. The European Organisation for Research and Treatment of Cancer (EORTC) 22921 four-arm randomised trial questioned the value of preoperative chemoradiation (XRT-CT) versus preoperative radiation (XRT) and the value of additional postoperative chemotherapy (CT) versus none in T3-T4 M0 resectable rectal cancer patients. We report on the preoperative toxicity, treatment compliance and early deaths (all deaths up to 30 days after surgery) of the two treatment modalities in patients who were entered into trial before January 2001. In the XRT Group (group A), patients received 45 Gy, 25 fractions over 5 weeks. In the XRT-CT Group (group B), two 5-day courses of CT were added to the first and fifth weeks of XRT. For each CT course: 5-fluorouracil (5-FU) 350 mg/m2/day and Leucovorin (LV) 20 mg/m2/day were given. 398 and 400 patients started treatment in groups A and B, respectively. Grade 2+acute diarrhoea occurred in 17.3 and 34.3% of patients in groups A and B, respectively (P<0.005). The other side-effects remained unchanged or were only marginally increased. The compliance with RT was 98.5 and 95.5% in groups A and B, respectively. In group B, 78.7 and 71.1% of the patients received 95-105% of the planned CT doses at the first and second courses, respectively. 6 patients died preoperatively, 2 from toxicity in group B. 8 patients (1%) died within the 30 days after surgery in both groups. At the doses recommended in the protocol, the addition of 5-FU-LV to preoperative XRT slightly increased the amount of acute toxicity. However, the compliance with the radiation protocol or the feasibility of surgery did not decrease. Much has been written about working with the dying. Few, if any, controlled studies have examined the application of principles set forth. The authors evaluate the effectiveness of working with dying cancer patients by assessing changes in quality of life, physical functioning, and survival. One-hundred twenty men with end-stage cancer were randomly assigned to experimental or control groups; the 62 experimental group patients were seen regularly by a counselor. Patients were assessed before random assignment and at one, three, six, nine, and 12 months on quality of live and functional status. Experimental group patients improved significantly more than the control group on quality of life within three months. Functional status and survival did not differ between groups. A subsample of lung cancer patients provided cross-validation of findings. Although survival was not expected to differ, it was predicted that functioning would be enhanced if quality of life improved. One interpretation is that little can be done to alter physical function and survival when intervention occurs late in the progression of a fatal disease. This in no way reduces the value of improving overall quality of life, since enhancing the quality of survival for end-stage cancer patients is a high priority medical goal. The purpose of the present study was to determine the safety and efficacy of induction chemotherapy followed by concomitant chemoradiotherapy. Thirty-eight patients were randomised to receive induction chemotherapy, consisting of cyclophosphamide and methotrexate followed by concomitant 5-fluorouracil and irradiation (study group) or irradiation alone (control group). There were non-significant differences in the initial tumor clearance rates in the two groups. Median disease-free survival (in complete responders) was 17 months (6-60+) vs 11 months (5-60+) (p = 0.407) and overall survival 11 months (1-60+) vs 14 months (2-60+) (p = 0.428) in the study and control groups respectively. Acute morbidity and deaths during intervention were higher in the study group (p = 0.007). This study suggests that induction along with concomitant chemoradiotherapy is too toxic for routine use and also fails to provide a survival benefit. The European Lung Cancer Working Party (ELCWP) designed a 3-arm phase III randomised trial to determine the role of accelerated chemotherapy in extensive-disease (ED) small-cell lung cancer (SCLC). Eligible patients were randomised between the 3 following arms: (A) Standard chemotherapy with 6 courses of EVI (epirubicin 60 mg m(-2), vindesine 3 mg m(-2), ifosfamide 5 g m(-2); all drugs given on day 1 repeated every three weeks. (B) Accelerated chemotherapy with EVI administered every 2 weeks and GM-CSF support. (C) Accelerated chemotherapy with EVI and oral antibiotics (cotrimoxazole). Primary endpoint was survival. 233 eligible patients were randomised. Chemotherapy could be significantly accelerated in arm B with increased absolute dose-intensity. Best response rates, in the population of evaluable patients, were, respectively for arm A, B and C, 59%, 76% and 70%. The response rate was significantly higher in arm B in comparison to arm A (P = 0.04). There was, however, no survival difference with respective median duration and 2-year rate of 286 days and 5% for arm A, 264 days and 6% for arm B and 264 days and 6% for arm C. Severe thrombopenia occurred more frequently in arm B but without an increased rate of bleeding. Non-severe infections were more frequent in arm B and severe infections were less frequent in arm C. Our trial failed to demonstrate, in ED-SCLC, a survival benefit of chemotherapy acceleration by using GM-CSF support. To perform a randomized study of the optimal timing of thoracic radiation (RT) as accelerated hyperfractionated radiation therapy (ACC HFX RT) in combination with concurrent chemotherapy (CHT) in limited-stage small-cell lung cancer (SCLC).
                Between 1988 and 1992, 107 patients were enrolled and 103 were assessable. All patients received ACC HFX RT with 1.5 Gy twice daily to 54 Gy plus concurrent daily carboplatin/etoposide (C/E) (30 mg each) and four sequential cycles of cisplatin/etoposide (PE) (30 mg/m2 and 120 mg/m2, respectively, on days 1 to 3). Group I patients (n = 52) received concurrent chemoradiation at weeks 1 to 4, and group II (n = 51) at weeks 6 to 9. Patients who showed a complete response (CR) or partial response (PR) underwent prophylactic cranial irradiation (PCI) at weeks 16 to 17.
                The median survival time was 34 months in group I and 26 months in group II, and the Kaplan-Meier 5-year survival rates were 30% and 15%, respectively. The difference was almost significant on univariate analysis (P = .052) and was significant on multivariate analysis (P = .027). Group I patients had a significantly higher local control rate than group II patients, but there was no difference between the two groups in distant metastasis rate. There was no difference in the incidence of acute or late grade 3 to 4 toxicity.
                Initial administration of thoracic ACC HFX RT with concurrent C/E seems to produce better local control and survival rates than delayed administration. We have recently reported the psychological outcome of a group Cognitive Behaviour Therapy (CBT) intervention with patients who had metastatic breast cancer. The data of 92 patients who were retained at the first follow-up assessment revealed short-term improvements on measures of mood and self-esteem amongst therapy participants. These changes were not sustained at the 3- and 6-month follow-up assessments. This report describes a survival analysis of 121 patients who entered the study, at 5 years after its commencement. The analysis, based on the Cox Proportional Hazards Regression model, revealed no survival advantage associated with the intervention. Only medical prognostic factors such as Eastern Cooperative Oncology Group (ECOG) performance status, visceral metastases and chemotherapy treatment significantly predicted patients' survival time. The findings of this study are compared with those of two earlier studies which also examined the survival effects of a group psychological intervention with metastatic breast cancer patients.
                Copyright 1999 John Wiley & Sons, Ltd. To compare the length of survival and quality of life in patients given combination chemotherapy in addition to supportive care and in patients given only supportive care.
                Randomised study.
                Gastrointestinal oncology departments.
                40 previously untreated patients with histologically confirmed, measurable colorectal cancer that was locally recurrent or metastatic.
                Patients were allocated randomly to receive chemotherapy or only supportive care in a ratio of 2:1 according to performance status, metastatic disease of the liver, and weight loss in the six months before entering the study. Chemotherapy consisted of four week cycles of intravenous leucovorin (200 mg/m2/day) followed by 5-fluorouracil (550 mg/m2/day) and cisplatin (20 mg/m2/day), each drug being given on the first four days of the cycle.
                Length of survival and quality of life score with an optimised functional living index-cancer scale.
                Overall survival was significantly longer for patients given chemotherapy (11.0 months) than for those receiving supportive care alone (5.0 months; p = 0.006). Despite common association of chemotherapy with mild to moderate gastrointestinal symptoms, there was no significant difference between the two groups in global or subgroup quality of life scores. In patients with abnormal scores before treatment, quality of life seemed better in the chemotherapy arm.
                In this sample of patients with disseminated colorectal cancer the chemotherapy regimen was an effective form of palliative treatment.
ESA treatment in cancer patients increased on study mortality and worsened overall survival. For patients undergoing chemotherapy the increase was less pronounced, but an adverse effect could not be excluded.