Critical Reviews in Oncology/Hematology 36 (2000) 9–12

Originality benefit and difficulty of clinical research in the WestJapan Lung Cancer Group

Masaaki Kawahara a*, Yutaka Ariyoshi b, Masahiro Fukuoka c, Kiyoyuki Furuse d

a Department of Medicine, National Kinki Central Hospital for Chest Diseases, Nagasone, Sakai, Osaka, 591-8555, Japanb Aichi Prefecture Hospital, Nagasone, Sakai, Osaka, 591-8555, Japan

c Kinki Uni6ersity, Nagasone, Sakai, Osaka, 591-8555, Japand Osaka General Hospital, Nagasone, Sakai, Osaka, 591-8555, Japan

Accepted 13 April 2000

Contents

1. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

2. Aims . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

3. Group structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

4. Originality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

5. Benefits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

6. Difficulties. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

7. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Reviewers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Biographies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

Abstract

The West Japan Lung Cancer Study Group (recently renamed the West Japan Thoracic Oncology Group) is a non-government,non-profit regional scientific organization whose objectives are to conduct clinical research and treatment of lung cancer, and topromote lung cancer expertise among thoracic physicians and radiologists in west Japan. Since 1990, a total of 46 institutes havejoined and established the rules of a society. Our major interests are phase II and III trials of chemotherapy in lung cancer. Wealso have participated in activities with the Japan Clinical Oncology Group (JCOG), which is supported by the National CancerCenter in Tokyo. Additionally, we have conducted phase II and III trials with the support of Japanese pharmaceutical companies.This support allows us to conduct reliable, large-scale randomized trials. Our organization’s main problems are unrefined datamanagement and few qualified statisticians, due in part to a lack of funding. © 2000 Elsevier Science Ireland Ltd. All rightsreserved.

Keywords: Lung cancer; Cooperative groups

www.elsevier.com/locate/critrevonc

* Corresponding author. Tel.: +81-722-523021; fax: +81-722-504034.E-mail address: kawahara@kinchu.hosp.go.jp (M. Kawahara).

1040-8428/00/$ - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved.PII: S 1 0 4 0 -8428 (00 )00094 -9

M. Kawahara et al. / Critical Re6iews in Oncology/Hematology 36 (2000) 9–1210

1. Introduction

Clinical trials undertaken by cooperative groups havebeen responsible for most of the major advances incancer treatment over almost four decades [1]. Clinicaltrials operated outside of the cooperative group systemlack a record of major accomplishments and the organi-zations that undertake them do not have the experience,expertise, or broad base of scientific resources to carryout landmark studies. Our group, established in 1988 asa small group located in the southern Osaka area, hasgreatly expanded. From 1990, 46 institutions in westernJapan joined together and established the rules of ourcooperative society. Our group is a non-profit, non-gov-ernment, regional scientific organization. Here, we ana-lyze and discuss the organization and working issues ofour group for the study of lung cancer.

2. Aims

The aims for the West Japan Lung Cancer StudyGroup are to conduct and develop clinical research forthe treatment of lung cancer, and to promote lungcancer expertise among thoracic physicians and radiolo-gists. Our major interests are phase I, II, and III studiesof chemotherapy and combined modality and relatedtreatments. Also, we conduct supporting care trials andnon-therapeutic investigation such as biological re-search.

3. Group structure

Last year, our group name was changed to the WestJapan Thoracic Oncology Group (current president: Y.Ariyoshi, MD; headquarters: Aichi Prefecture Hospi-tal). Our Data Management Center is located at KinkiUniversity, Osaka, where Dr M. Fukuoka is the Headof the Department of Medicine. The DMC is composedof one data manager, two assistants and a part-timestatistician. This center was established from April lastyear, and is limited to phase I and II studies at this time;large-scale randomized studies are not possible.

We currently have 46 participating institutes. At theadministrative level, our group consists of a steeringcommittee, executive committee, protocol reviewingcommittee, monitoring committee and fund raisingcommittee. Concerning the establishment of group pro-tocol, prior to the actual writing of first drafts, membersof the group must submit the study concept sheet to theprotocol committee. This sheet includes the establisheditems concerning trials in the group. The committeediscusses issues as follows:1. Is the study innovative, or does it repeat studies

done by other groups?

2. Is the study feasible for the group to pursue?3. Is there interest among the group members?4. How many patients are needed to complete the

study and what is the estimated accrual rate?Also, the protocol committee chairman should be in

close contact with the bio-statistician. If the protocolcommittee decides to develop the protocol, it does soaccording to the group’s guidelines for protocol asshown above. The next step is for the protocol-reviewcommittee to make revisions to the protocol draft. Thesteering committee then sends the protocol to investiga-tors and coordinators in the participating institutions.The coordinator submits the protocol to the IRB (Insti-tutional Review Board) in each institution, and finally,each institution’s chairman decides whether or not toparticipate in the study.

4. Originality

We started a large-scale phase III study of concurrentversus sequential thoracic radiotherapy and chemother-apy in stage III non-small cell lung cancer in 1992, and320 patients were enrolled. Study entry was completedin 1994. The preliminary results were presented at theASCO meeting in 1997, with final results published inthe Journal of Clinical Oncology in 1999 by Dr Furuse[2]. Data management and limited funding of the studywas supported by the JCOG (Japan Clinical OncologyGroup).

Our group also participated in a large-scale phaseIII study of irinotecan plus cisplatin versus vindesineplus cisplatin versus irinotecan alone for stage IIIB orIV non-small cell lung cancer, which included 450patients [3]. The aim of this study was to receiveevaluation after approval from the Japanese govern-ment. A pharmaceutical company supported this study,but funds were directly distributed to each participatinginstitution.

Other reports published to date: ‘Dose escalationstudy of carboplatin with fixed-dose etoposide plusgranulocyte-colony stimulating factor in patients withsmall cell lung carcinoma’ by Katakami [4]; ‘Phase IIstudy of irinotecan combined with cisplatin in patientswith previously untreated small-cell lung cancer’ byKudoh [5]; ‘Phase II study of 3-h infusion of paclitaxelin patients with previously untreated stage III and IVnon-small cell lung cancer’ by Furuse [6]; phase II studyof Amrubicin by Yana [7], CPT-11+etoposide forsmall-cell lung cancer by Nakamura [8]. On-going trialsinclude a randomized phase II trial of irinotecan+ tax-otere versus irinotecan+cisplatin for non-small celllung cancer, and a randomized phase II trial of carbo-platin+ irinotecan versus taxotere for relapsed non-small-cell lung cancer.

M. Kawahara et al. / Critical Re6iews in Oncology/Hematology 36 (2000) 9–12 11

5. Benefits

Benefits in cooperative research conducted by ourgroup include the ability to conduct large-scale ran-domized study with a high level of data reliance, theimprovement of overall study quality, and the develop-ment of new and effective treatments. Also, the addi-tional educational role of the cooperative group willensure that high standards of patient care are main-tained in participating institutions.

In Japan, there is a government founded cooperativegroup named JCOG [9,10]. The number of institutionswhich belong to this group and receive funding fromthe Japanese government is relatively small. Manyother institutions join JCOG studies as a cooperatingpartner, but they do not receive research funding fromthe government except for the expenses required fortheir transportation. These institutions may not belisted as co-authors. Because of this and other reasons,we decided to establish and newly organize our group,despite the fact that our resources are severely limited.Institutions in our group are now restricted to those inwestern Japan defined as the area west of Nagoya.

6. Difficulties

Our group established a Data Management Center inKinki University only recently (April 1998) because ofa lack of funding. The DMC is composed of one datamanager, two assistants and a part-time statistician. Atthis time, the function of this center is limited to phaseI and II studies, and it will require more time before wecan conduct large-scale randomized trials without aidfrom other resources. For example, as mentionedabove, we recently conducted two large-scale random-ized phase III trials of chemotherapy and combinedmodality treatment for non-small cell lung cancer. Inone trial, data management was supported by theJCOG, and limited financial support was given by theJapanese government. The other study of irinotecanwas supported by a pharmaceutical company.

We established a fund raising body in an attempt tocombat our weak financial position. Main financialsupport comes from the participating institutions them-selves, but this support is very small ($40 000 per year).Resources from new drug investigation conducted inour group is paid by pharmaceutical companies. How-ever, contracts are between the companies and individ-ual participating institutions, not the West Japan LungCancer Study Group itself, nor the participating physi-cians. This precludes our group from directly receivingfinancial resources. A few institutions receive researchfunding from the government because of participatingin trials conducted by the JCOG. However, this supportis very restricted.

Moreover, most physicians in our group are national,state or city employees, and therefore cannot conductfund raising activity, as per Japanese employee regula-tions. Other non-profit and non-government coopera-tive groups, such as the Japan Adult Leukemia StudyGroup, face similar problems with fund raising activity.To remedy this situation, a stable financial supportbody, which aims to obtain adequate funding for studyand members consisting of non-profit employees, mustbe established.

The West Japan Thoracic Oncology Group facesother difficulties. First, we have too few radiation on-cologists. Second, we do not have a full-time statisti-cian. There are few qualified statisticians in Japan, withone reason being Japanese universities don’t teach thesubject of bio-statistics. Third, our group does notinclude pathologists or thoracic surgeons; currently, weare encouraging their participation.

7. Conclusion

In conclusion, the main problem facing our relativelynew group in the field of clinical research is weakfinancial support, which has lead to, among otherthings, unrefined data management. Recently, theSWOG (Southwest Oncology Group, United States)lung cancer group has proposed an international coop-erative study of chemotherapy for lung cancer. Webelieve that international cooperative study such as thismay be the most effective way to overcome problemsassociated with conducting studies in Japan. We fullyrealize that our ability to become a better workingpartner for our international colleagues will be to theadvantage of all parties concerned.

Reviewers

This paper was reviewed by Prof. Jean-Paul Sculier,Institut Jules Bordet, Clinique de Reanimation Med-icale, Cancerologie Pulmonaire, Rue Heger-Bordet 1,B-1000 Brussels, Belgium, and Prof. Jean Klastersky,Institut Jules Bordet, Service de Medecine interne &Laboratoire d’Investigation, Clinique et d’OncologieExperimentale H.J. Tagnon, Rue Heger-Bordet 1, B-1000 Brussels, Belgium.

References

[1] Comis RL. The cooperative groups: past and future. CancerChemother Pharmacol 1998;42(suppl):S85–7.

[2] Furuse K, Fukuoka M, Kawahara M, et al. Phase III study ofconcurrent versus sequential thoracic radiotherapy in combina-tion with mitomycin, vindesine, and cisplatin in unresectable stageIII non-small-cell lung cancer. J Clin Oncol 1999;17:2692–9.

M. Kawahara et al. / Critical Re6iews in Oncology/Hematology 36 (2000) 9–1212

[3] Masuda N, Fukuoka M, Negoro S, et al. Randomized trialcomparing cisplatin (CDDP) and irinotecan (CPT-11) versusCDDP and vindesine (VDS) versus CPT-11 alone in advancednon-small cell lung cancer (NSCLC), a multicenter phase IIIstudy. Proc Am Soc Clin Oncol 1999;18:459a.

[4] Katakami N, Takada M, Negoro S, et al. Dose escalation studyof carboplatin with fixed-dose etoposide plus granulocyte-colonystimulating factor in patients with small cell lung carcinoma.Lung Cancer Study Group of West Japan. Cancer 1996;77:63–70.

[5] Kudoh S, Fujiwara Y, Takada Y, et al. Phase II study ofirinotecan combined with cisplatin in patients with previouslyuntreated small-cell lung cancer. West Japan Lung CancerGroup. J Clin Oncol 1998;16:1068–74.

[6] Furuse K, Naka N, Takada M, et al. Phase II study of 3-hinfusion of paclitaxel in patients with previously untreated stageIII and IV non-small cell lung cancer. West Japan Lung Cancer.Oncology 1997;54:298–303.

[7] Yana T, Negoro S, Takada Y, Yokota S, Fukuoka M. The WestJapan Lung Cancer Group: phase II study of amrubicin(SM-5887), a 9-amino-anthracycline, in previously untreatedpatients with extensive stage small-cell lung cancer (ES-SCLC):A West Japan Lung Cancer Group Trial. Proc Am Soc ClinOncol 1998;17:1734.

[8] Nakamura S, Kudoh S, Komuta K, et al. Phase II study ofirinotecan (CPT-11) combined eith etoposide (VP-16) forpreviously untreated extensive-disease small-cell lung cancer(ED-SCLC): A study of the West Japan Lung Cancer Group.Proc Am Soc Clin Oncol 1999;18:470a.

[9] Fukuda H, Niimi M. Current issue and perspectives in JapanClinical Oncology Group. Gan to Kagaku Ryoho 1999;26(suppl2):204–11.

[10] Shimoyama M, Fukuda H, Saijo N, Yamaguchi N. JapanClinical Oncology Group (JCOG). Jpn J Clin Oncol 1998;28:158–62.

Biographies

Masaaki Kawahara (Born: Wakayama, Japan; March3, 1948) Dr Kawahara is a medical oncologist andHead of the Division of Medicine at National Kinki

Central Hospital for Chest Diseases. He is an activemember of the American Society of Clinical Oncology,has been working on clinical research of diagnosis andtreatment of lung cancer for many years, and is theauthor of several articles and research reports in thisfield.

Yutaka Ariyoshi (Born: Nagano, Japan; September 8,1938) Dr Ariyoshi, a medical oncologist, is the Directorof Aichi Prefecture Hospital, and currently serves asvice president of West Japan Lung Cancer Group. Heis an active member of the American Society of ClinicalOncology. He has been working on clinical research ofdiagnosis and treatment of lung cancer and hematolog-ical diseases for many years, and is the author ofseveral articles and research reports in this field.

Masahiro Fukuoka (Born: Nara, Japan; August 151940) Dr Fukuoka is a medical oncologist and profes-sor of the 4th Department of Internal Medicine, KinkiUniversity School of Medicine. He is a member of theAmerican Society of Clinical Oncology and of theAmerican Association for Cancer Research. He hasbeen working on clinical research of anticancer newdrug and treatment of lung cancer, and is the author ofseveral articles and research reports in this field.

Kiyoyuki Furuse (Born: Shimane, Japan; January 14,1933) Dr Furuse is a medical oncologist and served asHead of the Division of Medicine at National KinkiCentral Hospital for Chest Diseases. He was the firstpresident of the West Japan Lung Cancer Group, andis an active member of the American Society of ClinicalOncology. He is also a Secretary General of this year’sWorld Conference of Lung Cancer (Tokyo). He has along and distinguished career in the field of clinicalresearch for the diagnosis and treatment of lung cancer,and his work has been widely published.

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