Use of Placebos in Delayed-Emesis Studies
Authors: Rudolph M. Navari, Paul J. Hesketh
Journal: Journal of Clinical Oncology (1999)

We read with great interest the recent article by Ko ¨hne et al 1 in the Journal of Clinical Oncology.The authors described the results of a trial with 236 patients with advanced colorectal cancer (ACC) randomized to receive high-dose fluorouracil (5-FU) weekly as a 24-hour infusion, combined with either folinic acid (arm A), interferon alfa-2b (arm B), or both modulators.Because of toxicity, mainly grade 4 diarrhea, reduction of the 5-FU dose by 20% was necessary in the three arms during the first or second cycle.The response rate was significantly higher for patients who received arm A (44%), especially in patients without previous adjuvant chemotherapy (48%).The median survival time for all patients was 15.1 months.A good result may be due in part to the selection of patients: 95% of the patients had Karnofsky performance status 80 to 100 at inclusion.Unfortunately, the article contains no data on quality of life (QL), although QL was measured in this study using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30), according to results presented at different meetings. 2,3 In an interim analysis based on the results of 194 patients, none of the 15 dimensions of QL improved during the course of treatment in any of the three study arms.The authors reported a significant deterioration of the following dimensions at week 8: physical functioning (arms B and C), social functioning (arm C), role functioning (arms A, B, and C) and global QL (arms A and C).Symptoms (anorexia, fatigue, nausea/vomiting, and diarrhea) worsened in all arms.To our knowledge, these are the first data indicating that 5-FU-based chemotherapy can deteriorate QL.Until now, literature has indicated that palliative chemotherapy in patients with ACC maintains or improves QL.Three randomized studies comparing chemotherapy and best supportive care have concluded that chemotherapy improves survival with maintained QL. [4][5][6] Data from at least eight prospective studies indicate that a high proportion (27% to 56%) of patients treated with chemotherapy have improved QL. 7 Improvement of QL was also recently proven with irinotecan as second-line chemotherapy in comparison to best supportive care. 8However, these studies included a mixture of symptomatic and asymptomatic patients.Asymptomatic patients are more likely than those with symptoms to show reduced QL because of the toxicity of therapy.This may be the case in the present study with high-dose infusional 5-FU.Moreover, the EORTC QLQ-C30 asks patients about the previous week, and patients receiving weekly treatment are more likely to report symptoms and toxicities.However, the weekly administration of chemotherapy has been associated with decreased QL in randomized studies compared with 3-times-a-week treatment in other tumors, such as breast cancer and small-cell lung cancer. 9-11QL seems to be an essential efficacy end point usefully supplementing toxicity outcome.We hope that the complete QL data will be published in another article, and we regret that the patients' point of view was not taken into account in this report.