Thoracic Oncology Division

Introduction
The number of lung cancer patients is rapidly increasing in Japan, and lung cancer has been the top cause of death in male patients since 1994. The majority of lung cancer patients are found at the advanced stage, and the prognosis of these patients is generally poor. It is extremely important to establish new effective treatments against advanced lung cancer.
The Thoracic Oncology Division has seven staff physicians, including two chiefs and two heads. A total of three chief residents and 13 residents joined the division during 2001. The focus of the division is to develop and to evaluate new treatments against advanced lung cancer and other thoracic malig-nancies. The division organizes a large clinical study group throughout Japan to develop rationally designed novel therapies and to establish the state-of-the-art therapy. The phase I study group was established in 1996, and several members of the Thoracic Oncology Division play a key role in the phase I group.

Routine Activities
The staff physicians of the Thoracic Oncology Division attend outpatient service for thoracic diseases. The division has 70-80 beds in the hospital. Inpatient care is carried out by five subteams. Each subteam consists of one staff physician and one or two residents. Two staff physicians and two residents in the Division are also members of the phase I team.
Protocol and case conferences are scheduled every Monday morning and afternoon, respectively. The journal club for thoracic oncologists is scheduled on Thursday mornings. A chest conference is held on Monday evening to discuss with thoracic surgeons, pathologists, and radiation oncologists.
A total of 378 new patients were admitted in 2001. Backgrounds and initial treatment of these patients in this year are shown in the table.
The treatment strategy for the patients is based on the established evidence and/or the clinical protocols approved by the institutional review board (IRB). Patients with stage IV non-small cell lung cancer are treated with combination chemotherapy with cisplatin plus new agent such as taxane, vinorelbine, gemcitabin or irinotecan. For locally advanced stage III non-small cell lung cancer, combined modality treatment with concurrent cisplatin-based chemotherapy plus thoracic radiotherapy is indicated. Combination chemotherapy with cisplatin plus irinotecan has been established as a new standard treatment against extensive stage small cell lung cancer based on the results of JCOG phase III trial. The standard treatment for patients with limited stage small cell lung cancer is cisplatin-etoposide chemotherapy with early concurrent twice-daily thoracic radiotherapy.

Research Activities
Research activities of the Thoracic Oncology Division can be divided into four diverse yet interrelated subjects: (1) clinical trials to evaluate new treatments against primary lung cancer and other thoracic malignancies; (2) pharmacokinetic and pharmacodynamic (PK/PD) analyses in phase I and II studies; (3) translational research from bench to beds or from beds to bench for the development of new treatment modalities; and (4) molecular and biochemical pharmacology.
Four combination phase I studies were conducted in patients with advanced non-small cell lung cancer to determine the recommended doses for 3-weekly combination regimens with paclitaxel(TXL) plus carboplatin(CBDCA) (Akiyama et al.), gemcitabin (GEM) plus cisplatin(CDDP) (Kusaba et al.), and vinorelbine(VNR) plus CDDP (Hotta et al.) and TXL plus CDDP. Based on the results of these studies, a multiinstitutional 4-arm phase III study in advanced non-small cell cancer (FACS trial) comparing TXL plus CBDCA, GEM plus CDDP, and VNR plus CDDP with irinotecan plus CDDP is now ongoing. In the phase I study of ZD1839, a epidermal growth factor receptor tyrosine kinase inhibitor, the maximum tolerated dose of ZD1839 was determined to be 700 mg/day by 28 days oral administration with dose limiting toxicities of diarrhea and transaminase elevation. A good response rate of 27.5 % was achieved in 102 Japanese patients with CDDP-refractory/resistant non-small cell lung cancer in the phase II study of ZD1839. The recommended doses of CDDP and VNR with concurrent thoracic radiotherapy for unresectable stage-III non-small cell lung cancer were determined to be 80 mg/m2 on day 1 and 20 mg/m2 on day 1 & 8, respectively. A phase II study of this chemoradiotherapy followed by single agent chemotherapy with docetaxel is ongoing. For extensive-stage small cell lung cancer, the results of phase III study of CPT-11 plus CDDP vs. etoposide plus CDDP (JCOG9511) are published in the N Engl J Med. (Noda et al.) Optimal schedule of three-drug combination with CPT-11, etoposide and CDDP is now under evaluation in a randomized phase II study. (JCOG9902) A multiinstitutional phase III study evaluating concurrent etoposide-CDDP chemo-therapy and twice-daily thoracic radiotherapy followed by CPT-11-CDDP chemotherapy for limited-stage small cell lung cancer will start in 2001, based on the promising results of a phase II study. (JCOG9903)

Clinical Trials
Clinical trials carried out in 2001 are shown in the table. Some studies are based on the research program of Japanese Clinical Oncology Group (JCOG), and some are carried out under contract with pharmaceutical companies. Approximately 60-70% of our inpatients are treated in clinical trials.

T. TAMURA

Clinical Trials Carried Out in 2001

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