1. www.***.com PHASE I TRIAL OF CONCURRENT CHEMORADIOTHERAPY USING DOXIFLURIDINE AND PACLITAXEL IN ADVANCED BREAST CANCER H.Hirowatari 1, K. Karasawa 1,2, K. Ito 1,2, T. Takada 1, H. Izawa 1, T. Furuya 1,2, S.Ozawa 1,2,C.Kurokawa 1,2 １ Department of Radiology, School of Medicine Juntendo University, 2 Department of Medical Physics for Advanced Radiotherapy, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 Japan

2. 2 Backgrounds Radiotherapy with concurrent chemotherapy has been used to increase local control in patients with advanced tumor. A variety of anti-cancer agents have been used, the optimal drug combinations, doses, and schedules have not yet been established. Concurrent chemoradiotherapy for breast cancer has been not popular.

3. Purpose We conducted phase I trial of concurrent chemoradiotherapy using Doxifluridine (5'- DFUR) and Paclitaxel (TAL) for advanced or recurrent breast cancer, which could admit the induction of d-ThdPase peculiarly only in the tumor for a radiation sensitizer. 3

4. Patients Eligibility Histologically documented cancer of the breast. Locally advanced inoperable breast tumor or a recurrent tumor requiring localized radiotherapy. Bone marrow function tolerance: WBC >4000/µL and 100000,Hb>9.5g/dl Expected prognosis:who will live more than 3 months. No infections. No severe respiratory complications. Pretreatment staging:CT or MRI of head, neck,chest abdomen and bone scintigraphy.

5. Treatment Methods Radiotherapy 60Gy/30f/6week (4-MV photon beam) 5’-DFUR 600mg/body five days/week TAL 20-35mg/m 2 twice/week Adjuvant therapy TAL 60mg/m 2 /week 5 5’-DFUR TAL Radiation MonTueWedThuFri

6. Patients Characteristics of the16 cases ( 2002.11-2005.5 ) Age 37-74y.o.(median 57) Menopausal status Pre3 Post13 Pathology IDC 15 ILC 1 Untreated fresh13 Pervious chemotherapy3 6

7. Unresectable advance primary tumor13 with axillary lymph nodes (Bilateral tumor1) Local recurrence3 Regional lymph node recurrence2 Chest wall recurrence1 Patients Status of the 16 cases ( 2002.11-2005.5 )

8. TAL Cases Level 120mg/m 2 6 Level 225mg/m 2 4 Level 330mg/m 2 3 Level 435mg/m 2 3 8 The Dosage Level of TAL

9. Adverse effects Hematological grade 01234 Leukocytes 45610 Neutrophils 74410 Lymphopenia 51730 Hb31000 Platelets 160000 Others Dermatitis 00880 Hair loss85120 Neuropathy100510 NCI CTCAEv3.0 9

10. Case:55y.o. T4cN1M0 TAL level:20mg/m 2 She died after 58 months because of metastatic disease from other primary, otherwise breast tumor had been controled. CR Pretherapy 4 months after treatment 10

11. Treatment Responses Irradiated siteCR10 PR 6 Overall CR6 PR 9 PD 1 11 Follow up period :10 to 53 months. (median 24)

12. Local Control Rate 61% 50% years provability

13. Overall Survival Rate 69% 60% years provability

14. 14 Summary Sixteen cases of inoperable advanced breast cancer had been treated with concurrent chemoradiotherapy. The treatment regimen consisting of TAL, 5’-DFUR and local radiotherapy. The dose of TAL 35mg/m 2 twice a week and 5'-DFUR of 600mg/body five times a week was tolerable. The treatment response of irradiated site, CR and PR were 10 and 6 case, respectively. Local control rates at 2 and 3 years after treatment were 61% and 50%, overall survival rates at 2 and 3 years after treatment were 69% and 60%, respectively.

15. Conclusions 15 The regimen consisting of concurrent dose of 600 mg of 5'-DFUR and doses of 35mg/m 2 twice a week of TAL was tolerable and effective in the local control of advanced or recurrent breast cancer.