6. Lara PN Jr, Natale R, Crowley J, et al: Phase III trial of irinotecan/cisplatin compared with etoposide/cisplatin in extensive-stage small-cell lung cancer: Clinical and pharma- cogenomic results from SWOG S0124. J Clin Oncol 27:2530-2535, 2009 7. Gandara DR, Kawaguchi T, Crowley J, et al: Japanese-US common-arm analysis of paclitaxel plus carboplatin in advanced non-small-cell lung cancer: A model for assessing population-related pharmacogenomics. J Clin Oncol 27:3540-3546, 2009 8. Iwasaki M, Kasuga Y, Yokoyama S, et al: Comparison of postmenopausal endogenous sex hormones among Japanese, Japanese Brazilians, and non- Japanese Brazilians. BMC Med 9:16, 2011 DOI: 10.1200/JCO.2012.45.9693; published online ahead of print at www.jco.org on January 22, 2013 ■■■ Inclusion of Patients With Advanced Cancer in Phase I Trials: Is This a Tool for Improving Optimism and Emotional Well-Being? TO THE EDITOR: Fu et al 1 recently published an article concern- ing the advance care planning for patients with cancer who are referred to early clinical trials. Via an investigator-designed survey, the authors assessed the attitudes of patients who were included in phase I clinical trials at the point of end-of-life planning. This study revealed that despite the severity of illness and lack of proven benefit from aggressive care in a phase I trial, a minority of these patients (49%) wanted to address advance care planning. Many of them avoided discussing this topic, with strong feelings in opposi- tion to considering advance care planning. Confronting the subject of planning for death was extremely traumatic for them because they remained hopeful that they could beat their cancer. Compared with similar patients with cancer, those who choose to be enrolled onto a phase I trial tend to be more optimistic than might be expected. 2,3 However, this result contrasts with the results of the recent study of Fang et al, 4 who reported that patients with cancer have an increased risk of suicide, particularly after a cancer diag- nosis, especially in those with a poor prognosis. On the other hand, two recent studies 5,6 hypothesized that depression was associated with worse survival in patients with metastatic cancer and that improvement in depression mediated a survival benefit. Therefore, how can we explain that, despite a short life expec- tancy, patients who choose to pursue treatment in phase I clinical trials remain optimistic? Critically, the authors hypothesized that this high degree of optimism could be generated by denial mechanisms in response to diagnosis and misconceptions about the therapeutic ob- jectives of phase I trials. In this way, the study reported by Fu et al 1 is of major interest and suggests the need for a fine balance between phase I trial patients’ optimism and the qualified chance of success of the protocol therapy. We previously reported the evaluation of sexuality, health- related quality of life (HRQoL), and depression in 63 patients with advanced cancer who were treated in phase I trials in the Gustave Roussy Institute Drug Development Unit. 7 To our knowledge, we reported the first prospective study evaluating sexuality, HRQoL, and depression in patients with advanced cancer who were treated in early clinical trials of predominantly targeted anticancer drugs. All of the patients enrolled onto phase I trials had advanced or metastatic cancer that was refractory to classic lines of chemother- apy. Interestingly, the prevalence of major depression was only 2%, respectively, at baseline and after 1 month of treatment. This result contrasts with the reported prevalence of major depression in the general healthy population of 5% 7 and in the cancer population of 10% to 25%. 8 In principle, we agree with the authors, 1 but we suggest that the disparity between patients’ optimism and the poor expectancy for success of the phase I trials could be explained in more detail. Arguably, patients who are eligible for entry in a phase I protocol have several specific characteristics, including good performance status, despite the failure of conventional chemotherapy and their progressing disease. Given that the key aim of phase I trials is to investigate toxicity and determine a recommended phase II dose, patients enrolled onto phase I trials are usually those for whom there is no standard therapy. Therefore, potential candidates for phase I trials are enrolled at a specific point along their disease trajectory when they may feel hopeless and experience fear of death. Moreover, participants have high expectations regarding the success of experimental therapy, with the hope for disease regression, and may discount potential toxicity. Available data on motivations and expectations of patients who are enrolled onto phase I clinical trials show that hope of a personal clinical benefit is the main reason patients agree to be included. 3 However, a central issue to be addressed is that most of the patients who are treated in a phase I trial for advanced cancer feel less depressed, with HRQoL scores that are comparable with those of the general healthy pop- ulation. Additional studies are needed to investigate the psycholog- ical impact of inclusion in early-phase clinical trials and the changes in depression symptoms from baseline to trial exit. Mathieu Rouanne Institut Gustave Roussy, Universite ´ Paris XI, Villejuif; Ho ˆ pital Foch, Suresnes; Universite ´ Versailles, Saint-Quentin-en-Yvelines, France Elodie Jacquelet and Antoine Hollebecque Institut Gustave Roussy, Universite ´ Paris XI, Villejuif, France Thierry Lebret Ho ˆ pital Foch, Suresnes; Universite ´ Versailles, Saint-Quentin-en-Yvelines, France Jean-Charles Soria and Christophe Massard Institut Gustave Roussy, Universite ´ Paris XI, Villejuif, France AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES 1. Fu S, Barber FD, Naing A, et al: Advance care planning in patients with cancer referred to a phase I clinical trials program: The MD Anderson Cancer Center experience. J Clin Oncol 30:2891-2896, 2012 2. Daugherty C, Ratain MJ, Grochowski E, et al: Perceptions of cancer patients and their physicians involved in phase I trials. J Clin Oncol 13:1062- 1072, 1995 3. Agrawal M, Grady C, Fairclough DL, et al: Patients’ decision-making process regarding participation in phase I oncology research. J Clin Oncol 24:4479-4484, 2006 Correspondence www.jco.org © 2013 by American Society of Clinical Oncology 817 Downloaded from jco.ascopubs.org on April 30, 2016. For personal use only. No other uses without permission. Copyright © 2013 American Society of Clinical Oncology. All rights reserved.