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PHASE I TRIAL OF CONCURRENT CHEMORADIOTHERAPY

USING DOXIFLURIDINE AND PACLITAXEL IN ADVANCED BREAST

CANCER

H.Hirowatari1, K. Karasawa1,2, K. Ito1,2, T. Takada1, H. Izawa1, T. Furuya1,2, S.Ozawa 1,2,C.Kurokawa 1,2

１ Department of Radiology, School of Medicine Juntendo University,2Department of Medical Physics for Advanced Radiotherapy, Graduate School of Medicine, Juntendo

University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 Japan

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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.

PurposePurpose

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.

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Patients EligibilityPatients 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 <10000/µL , Plt>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.

Treatment MethodsTreatment Methods

Radiotherapy 60Gy/30f/6week (4-MV photon beam)

5’-DFUR 600mg/body five days/week TAL 20-35mg/m2 twice/week

Adjuvant therapyTAL 60mg/m2/week

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5’-DFUR

TAL

RadiationMon Tue Wed Thu Fri

Patients Characteristics of the16 cases (2002.11-2005.5)

Patients Characteristics of the16 cases (2002.11-2005.5)

Age 　 　　　 　　　　　　　　　　　　　 37-74y.o.(median 57)Menopausal status Pre 3

Post 13

Pathology IDC 15 ILC 1

Untreated fresh 13Pervious chemotherapy 3 6

Unresectable advance primary tumor 13 with axillary lymph nodes (Bilateral tumor 1)

Local recurrence 3Regional lymph node recurrence 2Chest wall recurrence 1

Patients Status of the 16 cases (2002.11-2005.5)

Patients Status of the 16 cases (2002.11-2005.5)

TAL Cases

Level 1 20mg/m2

6

Level 2 25mg/m2

4

Level 3 30mg/m2 3

Level 4 35mg/m2

3

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The Dosage Level of TALThe Dosage Level of TAL

Adverse effectsAdverse effects

Hematological grade 0 1 2 3 4

Leukocytes 4 5 6 1 0Neutrophils 7 4 4 1 0Lymphopenia 5 1 7 3 0Hb 3 1 0 0 0Platelets 16 0 0 0 0

OthersDermatitis 0 0 8 8 0Hair loss 8 5 1 2 0Neuropathy 10 0 5 1 0

NCI CTCAEv3.0

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Case:55y.o. T4cN1M0Case:55y.o. T4cN1M0

TAL level:20mg/m2

She died after 58 months because of metastatic disease from other primary, otherwise breast tumor had been controled.

CRPretherapy 4 months after treatment

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Treatment Responses Treatment Responses

Irradiated site CR 10PR 6

Overall 　　　　 CR 6PR 9PD 1

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Follow up period :10 to 53 months. (median 24)

Local Control Rate Local Control Rate

61%50%

years

provability

Overall Survival RateOverall Survival Rate

69%60%

years

provability

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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/m2 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.

ConclusionsConclusions

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The regimen consisting of concurrent dose of 600 mg of 5'-DFUR and doses of 35mg/m2 twice a week of TAL was tolerable and effective in the local control of advanced or recurrent breast cancer.