Background: The aim of this study was to determine the maximum-tolerated dose (MTD) and the recommended dose of irinotecan and oxaliplatin with a fixed 5-fluorouracil (5-FU)/leucovorin (LV) regimen ...in patients with metastatic solid tumors. Patients and methods: The trial was designed to evaluate escalating doses of oxaliplatin and irinotecan, starting at 60 mg/m2 and 90 mg/m2, respectively, given at day 1 with the full-dose LV5FU2 regimen, given on days 1 and 2 as follows: folinic acid 200 mg/m2 followed by 5-FU 400 mg/m2 bolus and 600 mg/m2 22 h continuous infusion, every 2 weeks. The second cohort of patients was treated at the recommended dose for oxaliplatin and irinotecan with the simplified LV5FU regimen: on day 1, a 2-h infusion of folinic acid (400 mg/m2), followed by a 10-min intravenous bolus of 5-FU (400 mg/m2), followed by a continuous infusion of 5-FU (2400 mg/m2) over 46 h. Results: Thirty-four patients were treated at the following dose levels (oxaliplatin/irinotecan mg/m2): 60/90, 60/120, 85/120, 85/150, 85/180, 85/200 and 85/220 and seven patients were treated at the recommended dose with the simplified LV5FU scheme. The MTD was reached at dose level 85/220 mg/m2 but the recommended dose chosen for the second step was 85/180 mg/m2 to keep a better compliance with the biweekly schedule. Main grade 3/4 toxicities per patient included the following: neutropenia in 78% (febrile episodes in 12%), diarrhea in 27%, nausea/vomiting in 24% and peripheral neuropathy in 37% (Lévi’s scale). Antitumor activity was observed at almost all dose levels. Most objective responses were observed in digestive malignancies, since 10 out of 11 were obtained in five colorectal cancers, two pancreatic cancers, two cholangiocarcinoma and one gastric cancer. Conclusion: The recommended dose for the triple association is 85/180 mg/m2 of oxaliplatin and irinotecan, respectively, with LV5FU2 or simplified LV5FU. The antitumor activity in gastrointestinal malignancies should be evaluated in phase II studies in different tumor types.
Abstract With the recent trend of improved survival, there has been a marked interest in reviewing and refining the contribution of health related quality of life (HRQoL) outcome measures of ...treatment in advanced colorectal cancer. However, if HRQoL data are going to be of clinical value and help both physicians and patients make decisions there is a need for a consensus on both the design and methods of measurement of HRQoL in clinical trials, and an acknowledgement of the interpretation of the outcomes in clinical practice. Whilst it is encouraging to find that the quality of HRQoL measurement in clinical research has improved significantly over the last fifteen years, with a growing number of trial-based HRQoL studies, there is still the potential to improve the use of HRQoL in clinical decision making in advanced colorectal cancer. There is also the need to further refine measurement of HRQoL to provide useful data specific to these patients. It is anticipated that developments such as the liver metastases module EORTC (QLQ-LMC21) questionnaire will increase the sensitivity to change of the generic cancer measure, the EORTC QLQ-C30 and will provide essential HRQoL information regarding the use of treatments in both the curative and palliative settings. Furthermore, easy to use simple tools such as the “minimum standard checklist for evaluating HRQoL outcomes in cancer clinical trials” might be of help in guiding investigators on the basis of minimum criteria.
Abstract The aim of this study was to identify factors associated significantly with hospitalised cancer patients’ satisfaction with care. Patients were recruited from four geographical/cultural ...groups, including five European countries and Taiwan. They rated their level of satisfaction by completing the EORTC IN-PATSAT32 questionnaire at home. Additionally, data were collected on the sociodemographic and clinical characteristics and the quality of life of the patients, as well as on institutional characteristics. Of 762 patients recruited, 647 (85%) returned a completed questionnaire. The number of nurses and doctors per bed, institution size, geo-cultural origin, ward setting, teaching/non-teaching setting, treatment toxicity, global health status, participation in clinical trials and education level were all associated significantly at the multivariate level with satisfaction with doctor and nurse interpersonal skills, information provision, availability, and/or overall satisfaction. A number of patient-, institutional- and culture-related factors are associated with the perceived quality of cancer care. Future studies, with appropriate sampling frames and stratification procedures, are needed to better understand cross-national and cross-cultural differences in cancer patient satisfaction.
Quality of life (QL) is an important outcome in clinical trials in oncology. There is currently no valid international QL measure for gastric cancer. This paper describes the development of a QL ...module for gastric cancer to supplement the European Organization for Research and Treatment of Cancer (EORTC) Quality of life (QLQ-C30) questionnaire. Phases I to III of module development were conducted in the United Kingdom, France, Germany and Spain according to EORTC QL Group guidelines. Twenty relevant QL issues were generated from the literature and interviews with health professionals (n=24) and patients (n=58). This produced a 24 item provisional module. Further testing in 115 patients resulted in the QLQ-STO22, containing 22 questions, conceptualised into five scales and four single items, related to disease symptoms, treatment side-effects and emotional issues specific to gastric cancer. The use of the QLQ-C30 supplemented by the QLQ-STO22 will provide a comprehensive QL measure for international trials in gastric cancer.
The impact of treatment options on survival and late neurologic toxicity was investigated in a series of patients with primary cerebral lymphoma (PCL) and no known cause of immunosuppression.
...Prognostic factors for survival and treatment-induced late neurotoxicity were investigated in a retrospective series of 226 patients with PCL.
With a median follow-up of 76 months, the median overall survival was 16 months and 5-year survival was 19%. In a univariate analysis, age greater than 60 years, performance status, CSF protein level greater than 0.6 g/L, involvement of corpus callosum or subcortical grey structures, detectable lymphoma cells in CSF, increased serum lactate dehydrogenase (LDH), but not histological subtype, were significantly correlated with a poor survival. Treatment with chemotherapy versus radiotherapy alone (P = .05), high-dose methotrexate (HDMTX; P = .0007), and cytarabine (P = .04) correlated with a better survival in univariate analysis. Using the Cox model, age, performance status, and CSF protein were independently correlated with survival. After adjustment of these factors, treatment with an HDMTX-containing regimen remained the only treatment-related factor independently correlated with survival (P = .01). The projected incidence of treatment-induced late neurotoxicity was 26% at 6 years in this series, with a median survival from the diagnosis of late neurotoxicity of 12 months. Treatment with radiotherapy followed by chemotherapy was the only parameter correlated with late neurotoxicity in multivariate analysis (relative risk, 11.5; P = .0007).
Patients with PCL treated with regimens that included HDMTX followed by radiotherapy have an improved survival, but not a higher risk of late neurotoxicity as compared with other treatment modalities in this series.
Abstract Introduction Breast cancer is by far the most common form of cancer diagnosis in women. Cancer treatments are long, complex and often cumbersome with numerous side effects. Fatigue is now ...considered as the most distressing side effect of treatment. Fifty-eight percent to 94% of breast cancer patients experience fatigue during treatment with adjuvant chemotherapy. Objective The aim of this study is to identify the determinants of cancer-related fatigue, and the long-term effects of the different adjuvant treatments will be explored. Research design A prospective longitudinal study in women diagnosed for the first time with stage I-IIIA breast cancer and who have undergone surgery, has been designed to meet the study aims. Recruitment began in September 2008 and target enrolment completion date is December 2010. (clinicaltrials.gov number, NCT01064427). The MFI-20 ( Multidimensional Fatigue Inventory ) and the EORTC QLQ-C30 ( European Organization for Research and Treatment Quality of Life Questionnaire ) will be completed, at several times. The follow-up is planned over a 24-month period. We studied adjuvant chemotherapy regimens with anthracyclines or with anthracycline/taxane combination. The LOR ( Life Orientation Test ) will be completed only at baseline to estimate the level of optimism of the patient and the STAI ( State-Trait Anxiety Questionnaire ) will be filled to measure a stable propensity to experience anxiety, and tendencies to perceive stressful situations as threatening. Outcomes The knowledge of determinants should facilitate screening of fatigue, and its evaluation on consequences on the patients' quality of life would allow physicians better help patients cope with the management of fatigue according to the adjuvant regimen.
The aim of this study was to assess the validity of the French version of the Functional Assessment of Cancer Therapy – General (FACT-G), and to compare its psychometric properties with those of two ...other cancer-specific quality of life questionnaires, European Organisation for Research and Treatment of Cancer Quality of Life – Core 30 (EORTC QLQ-C30) and Functional Living Index – Cancer (FLIC). Two hundred and twenty three patients with breast or colorectal cancer completed the FACT-G questionnaire in French followed by (in random order) the QLQ-C30 and FLIC. An additional 87 patients with head and neck (H&N) cancer completed the FACT-H&N followed by the QLQ-C30 and H&N-Besançon. The French version of FACT-G was internally consistent, and its reproducibility was excellent. FACT-G Physical Well-Being and global scores correlated with all QLQ-C30 subscales. There was evidence of discriminant validity. Compared with the other tools, FACT-G included a statistically significantly higher proportion of items patients considered to be confusing or upsetting. Patients with breast or colorectal cancer expressed a preference for QLQ-C30. Use of the specific H&N additional items increased the responsiveness to change of FACT-G. The French version of FACT-G is valid and has psychometric properties similar to those of FLIC and QLQ-C30.
Patients with measurable or evaluable locally advanced or metastatic squamous cell carcinoma of the oesophagus were treated with cisplatin (CDDP), 100 mg/m
2, combined with 5-fluorouracil (5-FU) at a ...dose of 1000 mg/m
2 as a continuous infusion from days 1–5 (Arm A) or with CDDP alone (Arm B). Cycles were repeated every 3 weeks. 92 patients were randomised centrally, 88 were eligible. The response rate was 35% (95% CI (confidence interval), 20–54%) in Arm A and 19% (95% CI, 8–35%) in Arm B. One complete response was observed in each arm. The median duration of survival was 33 weeks and 28 weeks for Arm A and Arm B, respectively. Haematological and non-haematological toxicities were more frequent and more severe in Arm A. The most prominent toxicities were grade 4 aplasia and septicaemia (2), meningeal haemorrhage (1), cerebrovascular accident (3) and ischaemia of the lower limbs (1) all occurring in Arm A. Overall, seven treatment-related deaths (16%) were observed in Arm A, none in Arm B. The severe side-effects induced by the combination suggest that, currently, no standard chemotherapy can be recommended for patients with advanced squamous cell oesophageal cancer.
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