The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology.

BACKGROUND: In 1986, the European Organization for Research and Treatment of Cancer (EORTC) initiated a research program to develop an integrated, modular approach for evaluating the quality of life of patients participating in international clinical trials. PURPOSE: We report here the results of an international field study of the practicality, reliability, and validity of the EORTC QLQ-C30, the current core questionnaire. The QLQ-C30 incorporates nine multi-item scales: five functional scales (physical, role, cognitive, emotional, and social); three symptom scales (fatigue, pain, and nausea and vomiting); and a global health and quality-of-life scale. Several single-item symptom measures are also included. METHODS: The questionnaire was administered before treatment and once during treatment to 305 patients with nonresectable lung cancer from centers in 13 countries. Clinical variables assessed included disease stage, weight loss, performance status, and treatment toxicity. RESULTS: The average time required to complete the questionnaire was approximately 11 minutes, and most patients required no assistance. The data supported the hypothesized scale structure of the questionnaire with the exception of role functioning (work and household activities), which was also the only multi-item scale that failed to meet the minimal standards for reliability (Cronbach's alpha coefficient > or = .70) either before or during treatment. Validity was shown by three findings. First, while all interscale correlations were statistically significant, the correlation was moderate, indicating that the scales were assessing distinct components of the quality-of-life construct. Second, most of the functional and symptom measures discriminated clearly between patients differing in clinical status as defined by the Eastern Cooperative Oncology Group performance status scale, weight loss, and treatment toxicity. Third, there were statistically significant changes, in the expected direction, in physical and role functioning, global quality of life, fatigue, and nausea and vomiting, for patients whose performance status had improved or worsened during treatment. The reliability and validity of the questionnaire were highly consistent across the three language-cultural groups studied: patients from English-speaking countries, Northern Europe, and Southern Europe. CONCLUSIONS: These results support the EORTC QLQ-C30 as a reliable and valid measure of the quality of life of cancer patients in multicultural clinical research settings. Work is ongoing to examine the performance of the questionnaire among more heterogenous patient samples and in phase II and phase III clinical trials.

An EORTC Gastrointestinal Group evaluation of the combination of sequential methotrexate and 5-fluorouracil, combined with adriamycin in advanced measurable gastric cancer.

In a phase II multicenter trial, 71 patients with advanced measurable gastric cancer were registered to receive sequential high-dose methotrexate (MTX) and 5-fluorouracil (5-FU) combined with Adriamycin (A [Adria Laboratories, Columbus, OH]). The response rate was 33% (22 of 67), including all eligible patients. There were nine complete responders (CRs). The median survival for all patients was 6 months. There has been one toxic death; however, three other patients died from toxicity associated with major protocol violations. It is concluded that this protocol is active in gastric cancer. Toxicity, partly because of nonprotocol adherence, is considerable and is now under further investigation in a randomized trial comparing this schedule with a combination of 5-FU, Adriamycin, and mitomycin C (FAM).

An EORTC Gastrointestinal Group phase III evaluation of combinations of methyl-CCNU, 5-fluorouracil, and adriamycin in advanced gastric cancer.

In a prospective phase III multicenter trial, 189 patients with advanced measurable and nonmeasurable gastric cancer were randomized to receive 5-fluorouracil (5-FU) combined with Adriamycin (FA) or FA plus methyl-CCNU (MeFA). The response rate in patients with measurable disease was 10% (three of 29), and 18% (five of 28), respectively. No difference in the duration of survival was detected (P = .14; log rank test). Median survivals were 21 and 32 weeks, respectively. Toxicity was moderate, but there have been two toxic deaths among the patients who received FA. Because of the low response rate and the short survival, neither regimen can be recommended for the treatment of advanced gastric cancer.

Final results of a phase III clinical trial of adjuvant chemotherapy with the modified fluorouracil, doxorubicin, and mitomycin regimen in resectable gastric cancer.

PURPOSE: In a randomized clinical trial (European Organization for the Research and Treatment of Cancer [EORTC] no. 40813) on adjuvant chemotherapy in gastric cancer, results obtained after administration of the FAM2 regimen (fluorouracil [5-FU], doxorubicin, and mitomycin) were compared with results obtained after surgery alone to assess the effect of this regimen on overall survival, time to progression, and disease-free interval. PATIENTS AND METHODS: Three hundred fourteen patients who had undergone curative resection for stage II or stage III (International Union Against Cancer [UICC] 1978) gastric adenocarcinoma were randomized to receive chemotherapy (treatment arm) or no further treatment (control arm). The chemotherapy schedule was repeated every 43 days for seven cycles. The log-rank test and the Cox model were used for statistical analysis. RESULTS: Of 314 patients, 159 comprised the control group and 155 the FAM2 group. Nineteen FAM2 patients never received chemotherapy. The median number of cycles was five. Of the patients started on adjuvant treatment, severe hematologic and nonhematologic toxicity (grades 3 or 4, World Health Organization [WHO] scale) occurred, respectively, in 6% to 9% and in 1% to 29% of cases. The overall 5-year survival rate was 70% for stage II and 32% for stage III patients. No statistically significant difference was found between overall survival of the two treatment arms (P = .295). However, time to progression was significantly delayed in the FAM2 arm (P = .020) and disease-free survival showed borderline significance (P = .068). CONCLUSION: FAM2, in view of its high toxicity, cannot be advocated as standard adjuvant treatment for gastric cancer. Large-scale clinical trials using more active, less toxic regimens are required to demonstrate whether adjuvant chemotherapy provides any real benefit.

Evaluation of antiandrogen therapy in unresectable hepatocellular carcinoma: results of a European Organization for Research and Treatment of Cancer multicentric double-blind trial.

PURPOSE: The aim of the study was to evaluate the efficacy of antiandrogen therapy on overall survival and response in unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: A total of 244 patients with unresectable HCC were included in this multicentric double-blind trial. According to a two-by-two factorial design, patients were randomly assigned to receive one of the following treatments: pure antiandrogen plus placebo (A+P group, 60 patients); luteinizing hormone-releasing hormone (LHRH) agonist plus placebo (LHRH+P group, 62 patients); pure antiandrogen plus LHRH agonist (A+LHRH group, 62 patients); or placebo plus placebo (P+P group, 60 patients). Pure antiandrogen consisted of Anandron (Roussel-Uclaf Laboratory, Romainville, France) administered orally (300 mg daily for 1 month, then 150 mg daily). LHRH consisted of goseriline acetate (3.6 mg) or triptoreline (3.75 mg) administered monthly by subcutaneous injection. Treatment was given until death. Response was evaluated every 8 weeks according to World Health Organization (WHO) criteria. RESULTS: Six patients were considered ineligible. One patient had a complete response (A+P arm) and three had a partial response (two in the LHRH+P arm and one in the A+LHRH arm). An overall log-rank test did not demonstrate any significant difference in survival among the four arms. Taking the factorial design into account, comparison of survival showed no significant difference between Anandron-containing regimens and others, or between LHRH-containing regimens and others. No serious side effects occurred for any regimen. CONCLUSION: This controlled study shows clearly the lack of efficacy of androgen treatment in unresectable HCC.

Phase II study of cytarabine in Hodgkin's disease. The EORTC Lymphoma Cooperative Group.

Cytarabine was administered to 24 patients with previously treated Hodgkin's disease in the EORTC Lymphoma Cooperative Group. The drug was administered at the dose of 80 mg/m2 subcutaneously twice a day on 5 consecutive days every 3 weeks. The overall response rate was 17.6% (3 responses among 17 evaluable patients) with a short duration (2-6 months). The main toxicity was myelosuppression. Our experience in the EORTC Lymphoma Cooperative Group could not demonstrate a significant activity at this dose and schedule in Hodgkin's disease.

Activity of cisplatin in adenocarcinoma of the pancreas.

The activity of cisplatin in metastatic adenocarcinoma of the pancreas was assessed in 33 patients. Cisplatin was administered in a dose of 100 mg/m2, every 4 weeks. There were 2 complete responses and 5 partial responses (a response rate of 21%). The median duration of response was 5 months (range, 2+ to 15 months). Cisplatin is a modestly active drug in advanced pancreatic cancer.

Low-dose total body irradiation versus combination chemotherapy for lymphomas with follicular growth pattern.

The treatment of Non-Hodgkin's lymphomas with follicular growth pattern and advanced stage of disease remains controversial. Treatments varying from no initial treatment up to aggressive combination chemotherapy have been advocated. The EORTC Lymphoma Cooperative Group has performed a randomized prospective trial comparing short duration low dose total body irradiation (TBI) vs combination chemotherapy (CHVmP) + consolidation radiotherapy. Ninety-three patients were entered; of 84 evaluable patients, 44 received TBI and 40 CHVmP. Complete remission (CR) rates were 36%--TBI and 55%--CHVmP, but overall response rates were identical, 76 versus 69%. No significant difference in freedom from progression or survival was observed. No unexpected toxicity was seen. Although numbers are small, we cannot conclude that aggressive combination chemo-radiotherapy resulted in a better survival. Our analysis confirms that there is a constant risk of relapse. Other approaches should be explored if survival benefit is the ultimate goal in treatment of this patient population.

Adjuvant FAM2 in resectable gastric cancer.

In spite of the improvements in surgical techniques and intensive care, no important benefit in the prognosis of patients with gastric carcinoma has been attained in the last twenty years. Different adjuvant treatment protocols have been proposed in an attempt to improve upon the results obtained with surgery only. In western countries, the FAM chemotherapeutic regimen is one on the most widely used for the treatment of advanced gastric carcinoma. In 1982 the G.I. GROUP of the EORTC proposed a modification (FAM2) to the original FAM as an adjuvant treatment in a controlled clinical study for gastric carcinoma. It is still too early to determine any therapeutic advantages of FAM2 in this protocol. Although the FAM2 regimen is fairly well tolerated, there is some toxicity which, however, seems to be slightly higher than in the regular FAM. It remains to be seen if this is a reasonable price to pay for still unknown therapeutic advantages. In view of the scarcity of available data in this field and the conflicting results which have emerged so far, the results of our study are awaited with great interest.

[Familial cancer of the breast]. / Cancro da mama familiar.

Genetic, cultural and environmental factors are influences shared in familial breast cancer. The objective of this study was to evaluate the prevalence of familial breast cancer and its association with social and clinical characteristics of women. A hospital-based descriptive study was made, and 300 patients with the diagnosis of breast cancer, made in 1992, were investigated. 17,4% of the women had a history of familial breast cancer. The presence of a positive history for familial breast cancer was associated with high social level for post-menopausal women. Age at diagnosis was older for women whose affected relative was their sister, not their mother. The need for the continuing efforts of epidemiologists, pathologists and geneticists to recognize the explanatory model of the disease is emphasized.

EORTC trial non-Hodgkin lymphomas.

Results of an EORTC trial (20751) in non-Hodgkin lymphomas are presented. Patients were treated in the same way independent of the histological type. There were 468 patients in the study of whom 124 patients were in stage I (85% 5 year survival), 57 in stage II (55%), 121 in stage III (55%) and 166 in stage IV (45%). Using the Kiel classification the low grade lymphomas were subdivided into two categories: those with a follicular (80% 5 year survival) and with a diffuse cell pattern (50% 5 year survival) with an intermediate prognosis compared with the high grade lymphomas (35% 5 year survival). Treatment was stratified according to stage. In stage I regional radiotherapy was given followed by randomization for maintenance chemotherapy with Vincristine, Cyclophosphamide and Prednisone. No influence in survival was seen (85% at 5 years), although disease free survival was better in the maintenance chemotherapy group (75% vs 55% at 5 years). In stage II regional radiotherapy was followed, after randomization, by transdiaphragmatic irradiation, all patients received maintenance chemotherapy. The group was too small to draw conclusions about the effect of this treatment. Primary radiotherapy in stage II disease with diffuse histology gave bad results. Patients in stage III and IV were treated with 8 courses of chemotherapy with Adriamycin, VM26, Cyclophosphamide and Prednisone, given in two different time schedules. Iceberg radiation was then given to areas with initially large or slowly responding disease. All patients had maintenance chemotherapy. No difference was found for the 2 chemotherapy schedules in remission rate, disease free interval and survival. In stage III and IV patients with a follicular lymphoma have a longer relapse free interval and total survival (39% and 68% at 5 years) compared with those with a lymphoma diffuse histology (19 and 30% at 5 years). Patients with stage IV disease due to bone marrow involvement only had a better prognosis compared with stage IV disease for other reasons.