Phase I/II Trial of Partial Breast Irradiation With Concurrent Dose-Dense Doxorubicin and Cyclophosphamide (ddAC) Chemotherapy in Early Stage Breast Cancer: Report of Skin Toxicity and Cosmetic Outcome

Article Outline

• Purpose/Objective(s)
• Materials/Methods
• Results
• Conclusions
• Copyright

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Purpose/Objective(s) 

Anthracyclines are commonly used in the adjuvant setting for breast cancer, but prohibitive skin toxicity is observed when concurrently administered with radiation therapy (40% grade 4 radiation dermatitis-Fiets et al., Eur J Cancer, 2003). Potential benefits of adjuvant concurrent chemo-radiation include: shorter duration of overall therapy, greater efficacy from the delivery of therapy closer to surgery, and better local control via the radiation sensitizing effects of chemotherapy. With the advent of partial breast irradiation (PBI) and the associated limited radiation exposure, we hypothesized that the previously reported prohibitive toxicities of anthracycline-based chemotherapy and concurrent breast irradiation may no longer exist. Thus we conducted a single arm feasibility trial to evaluate the toxicity of PBI with concurrent chemotherapy and to generate preliminary local control data as background for a larger randomized efficacy trial.

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Materials/Methods 

Women with T1-2, N0-1 breast cancer with 3 mm lumpectomy margins were enrolled. Patients received PBI to the lumpectomy bed plus margin to a total dose of 40.5 Gy (2.7 Gy delivered daily for 15 fractions). The PBI was concurrent with the first 2 of planned 4 cycles of dd AC (60 and 600 mg/m² respectively delivered every 14 days with colony-stimulating factor support). The primary endpoints of skin/soft tissue toxicities were graded by the treating physician and nurse according to the Common Terminology Criteria for Adverse Events manual (version 3.0). The cosmetic outcomes were graded by a panel of 8 healthcare professionals using the commonly accepted Harvard Cosmetic scale. Digital photographs at baseline, during and q 3–6 months after PBI were obtained for comparison. Additional, systemic therapy after dd AC was given at the physician's discretion. A frequency of grade 4 radiation dermatitis ≥20% was considered unacceptable and would prompt early closure of the trial.

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Results 

Twenty-two patients enrolled between 11/04 and 1/07 and have completed radiation and chemotherapy. Median tumor size was 1.8 cm (range 0.4–3.0 cm), 62% were pN0 and 50% had ER positive disease. With a median f/u of 16 months (range 3–29 months), there have been no local or systemic recurrences. Eighty-one percent of the patients developed Grade 1 radiation dermatitis. None developed radiation dermatitis > Grade 1 (one-sided 95% CI [0%,13%]) or radiation recall. The cosmetic outcome at the completion of radiation and at the 6 month follow-up was graded good to excellent in 95% and 100% of the patients respectively, when compared to pre-treatment images. There has been no late soft tissue or skin toxicity thus far.

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Conclusions 

These preliminary results suggest that PBI with concurrent dd AC is tolerable. There is strong evidence that the rate of grade 2, 3, or 4 radiation dermatitis is less than 15% (one-sided p = 0.03) and the cosmetic outcome is acceptable. Further follow-up is needed to determine the risk of late toxicity and the long term cosmetic outcome.

(Funded by The Breast Cancer Research Foundation)