Capecitabine (Xeloda) enhanced photodynamic therapy for treatment of breast cancer and its metastases in a murine breast tumor model (Conference Presentation)

Sanjay Anand; Anton Yasinchak; Taylor Bullock; Mukul Govande; Edward Maytin

doi:10.1117/12.2525564

14 August 2019 Capecitabine (Xeloda) enhanced photodynamic therapy for treatment of breast cancer and its metastases in a murine breast tumor model (Conference Presentation)

Sanjay Anand, Anton Yasinchak, Taylor Bullock, Mukul Govande, Edward Maytin

Author Affiliations +

Proceedings Volume 11070, 17th International Photodynamic Association World Congress; 110702E (2019) https://doi.org/10.1117/12.2525564
Event: 17th International Photodynamic Association World Congress, 2019, Cambridge, Massachusetts, United States

Abstract

Breast cancer (BCA) in women is a leading cause of mortality and morbidity with distant metastases occurring in ~40% of cases. Here, as an alternative to ionizing radiation therapy and chemotherapy and their associated side effects, we explored a new combination approach using capecitabine (CPBN) and aminolevulinate-based photodynamic therapy (PDT). We have recently shown that a combination PDT approach in which 5-fluorouracil (5FU), a differentiation-promoting agent, increases the levels of PpIX in cancer cells when given as a neoadjuvant prior to ALA. However, 5FU can be toxic when administered systemically at high levels. We reasoned that CPBN, a known chemotherapeutic drug for BCA and less toxic than 5FU (because CPBN is metabolized to 5FU specifically within tumor tissues), might work equally well as a PDT neoadjuvant. Murine 4T1 BCA cells harboring a luciferase transgene were injected into breast fat pads of female nude mice. CPBN (600 mg/kg/day) was administered by oral gavage for 3 days followed by intraperitoneal ALA administration and PDT with red light (633 nm) on day 4. Tumor growth and regression were monitored in vivo using bioluminescence imaging. Histological changes in primary tumors and metastases were assessed after necropsy. CPBN pretreatment of 4T1 tumors increased cellular differentiation, reduced proliferation, raised PpIX levels, enhanced tumor cell death, and reduced metastatic spread (incidence and tumor load) of 4T1 cells post-PDT, relative to vehicle-only controls. The use of CPBN as a non-toxic PDT neoadjuvant for treatment of BCA represents a novel approach with significant potential for translation into the clinic.

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Sanjay Anand, Anton Yasinchak, Taylor Bullock, Mukul Govande, and Edward Maytin "Capecitabine (Xeloda) enhanced photodynamic therapy for treatment of breast cancer and its metastases in a murine breast tumor model (Conference Presentation)", Proc. SPIE 11070, 17th International Photodynamic Association World Congress, 110702E (14 August 2019); https://doi.org/10.1117/12.2525564

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KEYWORDS

Photodynamic therapy

Tumors

Breast

Breast cancer

Tumor growth modeling

Cancer

In vivo imaging

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