Treating IIA/B Seminoma With Combination Carboplatin and
Transcrição
Treating IIA/B Seminoma With Combination Carboplatin and
VOLUME 27 䡠 NUMBER 12 䡠 APRIL 20 2009 JOURNAL OF CLINICAL ONCOLOGY Study of Newspaper Reports Regarding Clinical Trials in Japan C O R R E S P O N D E N C E A E a ch P a pe r T otal 450, 000 1, 600, 000 TO THE EDITOR: Clinical trials are necessary for the development 400,000 1,400,000 of new drugs and treatment methods. To conduct clinical trials smoothly, it is essential to improve public awareness of clinical trials. Accordingly, information regarding clinical trials must be disclosed and provided to the public in an understandable form. However, in Japan, 50% of patients in general and 70% of all participants in clinical trials have stated that the amount of information regarding clinical trials is scarce,1 and people perceive the information services related to clinical trials to be deficient. The mass media, including newspapers and television broadcasts, are effective means of providing information to the public. In Japan, 8.3% of the television audience is equivalent to approximately 3 million people,2 and the circulation of major newspapers ranges from 2.2 million to 10 million per day. Therefore, the use of mass media facilitates the provision of information to a large number of people at once. On the other hand, cooperation from mass media is necessary to improve public awareness of medical care.3-5 However, many physicians appear to be dissatisfied with the media reports regarding medical care.2 Therefore, it cannot be said that the relationship between these two parties is favorable. To conduct clinical trials effectively, cooperation from mass media is essential. However, there have not been any studies that have systematically investigated mass media reports regarding clinical trials, so the situation thereof is unknown. We used the most up-to-date newspaper database to examine the situation of reports on clinical trials in the major Japanese newspapers. Our study was directed at the five major newspapers in Japan (ie, Asahi, Mainichi, Yomiuri, Sankei, and Nihon Keizai). The total number of subscribers to these newspapers is 27 million per day. The largest newspaper database in Japan, Nikkei Telecom, was used to obtain article information. This database incorporates articles from almost all newspapers that are issued in Japan, including every article in the five major newspapers since 1992. First, using a thesaurus search of Igaku Chuo Zasshi (Japan Medical Abstracts), we extracted words related to clinical trials to define the following words as keywords: investigational agent, preclinical study, drug screening, nonclinical test, clinical trial, sponsored study, clinical protocol, prospective study, comparative test, blind study, phase I study, phase II study, phase III study, phase IV study, postmarketing surveillance, randomized clinical trial, Good Clinical Practice, Good Laboratory Practice, clinical research coordinator, institutional review board, and clinical investigator. To investigate the number of articles related to clinical trials and the reported content, the articles published by the five major Japanese newspapers from 1992 to 2007 were then examined for the number of articles that contained these keywords, annual change, and content. 350,000 Journal of Clinical Oncology, Vol 27, No 12 (April 20), 2009: pp 2099-2108 1,200,000 M 300,000 1,000,000 A Y 250,000 800,000 200,000 S 600,000 150,000 N 100,000 400,000 50,000 200,000 0 06 20 02 04 20 20 00 20 98 19 96 19 94 19 19 92 0 B 400 1, 600 350 1,400 300 1,200 250 1,000 200 800 150 600 100 400 50 200 0 06 20 04 20 02 20 00 20 98 19 96 19 94 19 19 92 0 Fig 1. (A) Total number of articles in five major newspapers. (B) Number of clinical trial–related articles in five major newspapers. Bar, five newspapers taken together; A, Asahi; M, Mainichi; Y, Yomiuri; S, Sankei; N, Nihon Keizai. Figure 1A shows the annual change in the total number of articles in the five major newspapers. Although the total number of articles had been increasing from the early 1990s, there was almost no change after 2000. After 2000, the total number of articles in the Yomiuri, Asahi, and Mainichi newspapers was approximately three times that in Nihon Keizai and Sankei. Figure 1B shows the change in the number of clinical trial–related articles in the five major newspapers. The proportion of the number of clinical trial–related articles among the total number for all five major newspapers temporarily increased to 0.167% in 1996 (Fig 2). The number of such articles in Nihon Keizai increased after 2000. The number of such articles in Sankei reached a slight peak in 2002. Most of the articles in Nihon Keizai were related to the performance of pharmaceutical companies, such as the development of new drugs. For the four other papers, the proportion of the number of articles in the other periods remained constant at about 0.07%. Figure 3 shows the peak year for the appearance of each keyword. The major keywords appeared most frequently in 1994 and © 2009 by American Society of Clinical Oncology Downloaded from ascopubs.org by 78.47.27.170 on January 20, 2017 from 078.047.027.170 Copyright © 2017 American Society of Clinical Oncology. All rights reserved. 2099 No. of Clinical Trial-Related Articles (%) Correspondence 0.30 Y 0.25 N 0.20 S 0.15 0.10 0.05 A M 0.00 1992 1994 1996 1998 2000 2002 2004 2006 Year Fig 2. Ratio of clinical trial–related articles to the total number of articles. Bar, five newspapers taken together; A, Asahi; M, Mainichi; Y, Yomiuri; S, Sankei; N, Nihon Keizai. 1996. The peak year for the appearance of words related to the methodology of clinical trials, such as phase and protocol, was 1994. The peak year for the appearance of words such as the Ministry of Health, Labour and Welfare; lawsuit; Pharmaceutical Affairs Law; clinical trial; ethics; and others was 1996. Our study revealed that in the newspapers, clinical trial–related articles occupied a certain space but accounted for a small proportion of total articles. In the five major newspapers, the percentage of clinical trial–related articles among all articles was approximately 0.07%, 0.1000 10 15 14 11 13 1 12 12 5 Percent 0.0100 2 3 4 7 9 16 0.0010 8 20 06 20 04 20 02 00 20 19 98 19 96 19 94 19 92 0.0001 Fig 3. Peak year of the ratio of articles containing each keyword to the total number of articles. (yellow circle) phase-related words; (blue square) procedurerelated words; (red ⫻) political words; (blue triangle) others. 1, phase I study; 2, phase II study; 3, phase III study; 4, phase IV study; 5, preclinical test; 6, randomization; 7, protocol; 8, Good Clinical Practice; 9, coordinator; 10, Ministry of Health, Labour and Welfare; 11, Pharmaceutical Affairs Law; 12, guideline; 13, ethics; 14, investigational drug; 15, lawsuit; 16, doctor-led model clinical trials. 2100 which means that two or three articles were disseminated per day. As the aging of Japanese society progresses, public awareness of medical care has been increasing. Many clinicians seem to think that this has resulted in an increasing number of clinical trial–related reports in the major newspapers. However, despite these anticipations, the proportion of such articles remained substantially unchanged in the four newspapers other than Nihon Keizai, except for a temporary peak in 1996. That is, despite the efforts of the medical community, the number of clinical trial–related articles did not increase in the general readership newspapers. Considering the fact that many people obtain medical information from newspapers, it would be difficult to believe that there have been recent improvements in public awareness of clinical trials. Significant differences were observed in the percentage of clinical trial–related articles by newspaper company. In particular, it is interesting that Nihon Keizai recently showed an increasing percentage of clinical trial–related articles. From 2002 to 2007, the percentage of clinical trial–related articles became more than double the percentage in the 1990s. Nihon Keizai is an economic paper, so it regards pharmaceutical companies as a growing field in Japan, and thus reports on clinical trials from the perspective of investment and pharmaceutical industry performance. Health care professionals rarely view clinical trials from the perspective of investment and economic growth. Therefore, there may be some discrepancies between their perspective and that of the public. The number of clinical trial–related articles increased sharply in 1996. This was because in the same year, HIV-tainted blood scandals6 and cases of drug-induced Jacob’s disease7 became social problems. Furthermore, in 1994, misconduct in a clinical trial for sorivudine8 led to a social problem, resulting in an increased number of related articles. These facts conform to the tendency of mass media to prefer to deal with incidents and new events. In 1994 and 1996, there was an increased appearance of words related to the methodology of clinical trials such as phase II and phase III as well as keywords such as the Ministry of Health, Labour and Welfare; lawsuit; Pharmaceutical Affairs Law; clinical trial; and ethics. Therefore, it is believed that people were exposed to information regarding the methodology of clinical trials and the administrative role of pharmaceutical affairs via news reports on medication scandals and misconduct in clinical trials. It is undeniable that the reports of major newspapers on clinical trials in relation to medication scandals and misconduct could possibly have an influence on the formation of negative public impressions regarding clinical trials. On the other hand, in Japan, the system of clinical trials has developed greatly since 2000, and the Pharmaceutical Affairs Law was amended considerably in 2002.9,10 Our study found that the appearance of certain keywords reached a peak during that time: coordinator in 2002, and doctor-led model clinical trials in 2005. During this period, there were no major medication scandals or incidents of misconduct. These keywords were used in articles regarding amendments of the system of clinical trials. It should be noted here that the number of reports with these keywords (coordinator and doctor-led model clinical trials) was approximately 10% that of reports on medication scandals in 1996. This fact means that the administration of pharmaceutical affairs and discussions regarding the system of clinical trials may be reported in the newspapers, but only with a small amount of text. Therefore, in comparison with the topics of medication scandals and misconduct, it may be difficult to promote public understanding © 2009 by American Society of Clinical Oncology Downloaded from ascopubs.org by 78.47.27.170 on January 20, 2017 from 078.047.027.170 Copyright © 2017 American Society of Clinical Oncology. All rights reserved. JOURNAL OF CLINICAL ONCOLOGY Correspondence regarding the systemic reform of clinical trials. Taking these facts into consideration, to enhance public understanding regarding clinical trials, it may be important to utilize means of providing information other than newspapers, which often emphasize medication scandals and misconduct. Our study shows that clinical trials are topics that the major newspapers report. However, many of the newspaper reports emphasize the performance of pharmaceutical companies and incidents of misconduct, such as medication scandals, while providing insufficient information regarding the system of clinical trials. It is recommended that health care professionals fully understand these characteristics of the major newspapers. Morihito Takita Division of Social Communication System for Advanced Clinical Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan Hiroto Narimatsu Division of Social Communication System for Advanced Clinical Research, The Institute of Medical Science, The University of Tokyo; Division of the Strategic Outcome Research Program for Cancer Control, Ministry of Health, Labour and Welfare Commission, Japan Cancer Society, Tokyo, Japan Tomoko Matsumuira and Yukiko Kishi Division of Social Communication System for Advanced Clinical Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan Tamae Hamaki, Yuko Kodama, Koichiro Yuji, Yuji Tanaka, and Masahiro Kami Division of Social Communication System for Advanced Clinical Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES 1. Saito K, Kodama Y, Ono S, et al: Current status of quality in Japanese clinical trials. Contemp Clin Trials 26:503-509, 2005 2. Matsumura T, Yuji K, Nakamura T, et al: Possible impact of the NHK special questioning cancer treatment in Japan on clinicians’ prescriptions of oxaliplatin. Jpn J Clin Oncol 38:78-83, 2008 3. Grilli R, Ramsay C, Minozzi S: Mass media interventions: Effects on health services utilisation. Cochrane Database Syst Rev 1:CD000389, 2002 4. Tian Y, Robinson JD: Media use and health information seeking: An empirical test of complementarity theory. Health Commun 23:184-190, 2008 5. Bala M, Strzeszynski L, Cahill K: Mass media interventions for smoking cessation in adults. Cochrane Database Syst Rev 1:CD004704, 2008 6. Swinbanks D: Documents confirm delays in Japanese HIV blood scandal. Nature 379:760, 1996 7. Dillner L: BSE linked to new variant of CJD in humans. BMJ 312:795, 1996 8. Swinbanks D: Deaths bring clinical trials under scrutiny in Japan. Nature 369:697, 1994 9. Saito K, Kodama Y, Ono S, et al: Quality of Japanese clinical trials estimated from good clinical practice audit findings. Am J Ther 13:127-133, 2006 10. Saito K, Kodama Y, Ono S, et al: Reliability of Japanese clinical trials estimated from GCP audit findings. Int J Clin Pharmacol Ther 46:415-420, 2008 Naoko Murashige DOI: 10.1200/JCO.2008.21.3967; published online ahead of print at www.jco.org on March 16, 2009 Ministry of Health, Labour and Welfare, Aide of the Minister, Health Sector Reform Office, Tokyo, Japan ■ ■ ■ Treating IIA/B Seminoma With Combination Carboplatin and Radiotherapy TO THE EDITOR: Garcia-del-Muro et al1 recently reported results from treating 72 patients with IIA/B seminoma with combination chemotherapy, giving a 5-year progression-free survival of 90% (95% CI, 82% to 98%) and overall survival of 95% (95% CI, 89% to 100%). Concluding that combination chemotherapy avoided long-term risks associated with radiotherapy (RT) they suggested this as an alternative treatment. While accepting these results, we remain unconvinced that this is a significant step forward in treating this patient group. In addition to the significant acute toxicity, combination chemotherapy for testicular cancer leads to a well-documented two-fold increased risk of cardiovascular disease.2-4 Chemotherapy is also (as for RT) associated with significant increases in second malignancy. Overall the odds ratio favors RT: subdiaphragmatic RT increases the risk of major late complication (second malignancy or cardiovascular disease) by 1.8-fold (95% CI 1.3- to 2.4-fold), whereas chemotherapy increases this risk by 1.9-fold (1.4- to 2.5-fold).5 Further the risk of second malignancy after subdiaphragmatic RT may be reduced by as much as half if treatment is restricted to the para-aortic region.6 Historically, the main stay of treatment has been RT to the paraaortic and ipsilateral pelvic lymph nodes. A review of 313 patients from seven studies with IIA/B seminoma treated with RT alone sugwww.jco.org gested 22 relapses: a crude relapse rate of 7%,7 though the risks may be higher in stage IIB disease and after relapsing on surveillance; 5-year relapse-free survivals (RFSs) from our previous report of 80 patients treated with RT alone were 84.9% for IIA and 69.4% for IIB.8 We agree that improving outcomes achieved by RT is a worthwhile goal, but believe this can be achieved without resorting to initial combination chemotherapy. We have previously published a series of 33 patients with seminoma stage IIA/B treated with carboplatin (one or two cycles) and RT between 1989 and 1997, achieving a 5-year RFS of 96.9%.8 Subsequently, since 1997, we have treated a further 29 patients (13 IIA and 16 IIB, including three patients who had relapsed while on surveillance for stage I disease). Twenty-eight patients received carboplatin dosed at area under curve (AUC) 7, one patient AUC6. With respect to RT, all patients received 30Gy in 15# MPD administered with 6 MV photons, over 3 weeks, commencing 4 weeks after administration of the carboplatin. RT fields treated the para-aortic (from D10/11 interspace to L5/S1) lymph nodes. The first five patients treated in this series received a boost to the involved node of 5Gy in 3 fractions over 3 days. No relapses have been observed with a median follow-up of 3.4 years (range, 0.6 to 7.5 years), giving a 3-year RFS of 100% (95% CI, 75.3% to 100%). One patient required surgical removal of residual radiological abnormality via retroperitoneal lymph node dissection. Histology from this tissue revealed elements of differentiated teratoma and histological review of the original orchidectomy specimen in the light of this revealed differentiated teratoma in the primary tumor. In stage I disease, the efficacy of carboplatin in safely eliminating clinically undetectable metastatic disease has been demonstrated in a © 2009 by American Society of Clinical Oncology Downloaded from ascopubs.org by 78.47.27.170 on January 20, 2017 from 078.047.027.170 Copyright © 2017 American Society of Clinical Oncology. All rights reserved. 2101