Interpreting the results of clinical trials of cancer chemotherapy: the importance of reporting concurrent supportive care.
Authors: Freedman OC , Zimmermann C , Clemons MJ 
Published: December 2010

Abstract
Abstract #6138
Background: Important outcomes for cancer patients depend not only on anti-cancer treatment, but also on supportive measures that aim to alleviate symptoms of cancer or side effects due to therapy. A comparison of cancer therapies that is evaluated in a randomized clinical trial (RCT) may therefore be significantly confounded by differences in supportive treatments between trial arms.&#x2028; Methods: We performed a systematic review of the past 5 years of randomized, phase III trials evaluating breast cancer chemotherapy to assess the prevalence of confounding effect of differential use of supportive treatments. We identified publications in MEDLINE (OVID: 1996-week 3 2008) using the search terms: exp breast neoplasms/dt; limit to clinical trial, phase III, limit to year 2003-2008. Inclusion criteria were phase III clinical trials with at least one of the following outcomes: nausea, vomiting, febrile neutropenia, infection, diarrhea, pain.&#x2028; Results: We identified 202 studies from the initial search. 62 studies met inclusion criteria; 32 trials involved women with advanced breast cancer, and 30 trials involving women withearly breast cancer. All trials were open-label. Significant differences were reported between trial arms for the incidence of: nausea or vomiting (14 trials, 23%), febrile neutropenia (14 trials, 23%), grade 3-4 diarrhea (7 trials, 11%), and myalgia, arthralgia, or pain ( 5trials, 8%). Fifty-two studies (82%) did not report the antiemetics used, and only 5 studies (8%) reported the type, dose, and frequency of antiemetics. Twenty-four trials (39%) did not report whether prophylaxis growth factors could be used , 24 trials (39%) indicated whether primary or secondary prophylaxis was allowed, and only 5 trials (8%) reported both the dose and the type of growth factor used in all arms of the trial. Twenty-one trials (33%) provided at least minimal guidelines regarding the use of antibiotics for prophylaxis of febrile neutropenia. One trial stated that anti-diarrhea treatment was used according to guidelines established for the anticancer therapy. No trial reported guidelines for treatment of pain, myalgia, or arthralgia.&#x2028; Discussion: Despite substantial differences demonstrated in important outcomes of toxicity, a minority of phase III trials report guidelines for use of supportive medication. Since all of the phase III trials were open-label, patients in one arm of the trial may receive different supportive treatments than those in other arms, leading to potential confounding of the results. Differences in supportive treatment are especially important for trials in advanced breast cancer, where symptom control is a major goal of treatment. In order to minimize confounding in cancer chemotherapy trials, guidelines for the type, dose, and frequency of supportive care drugs should be provided and the percent of patients in each arm of the trial receiving these medications should be reported.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6138.