Cutaneous metastasis (CM) occurs in 20% of patients with breast carcinoma (BCA), and is extremely difficult to treat.
These CM are relatively resistant to chemotherapy, generally responding only to ionizing radiation (IR). Multiple rounds
of IR, however, lead to debilitating fibrosis and radiation dermatitis. An alternative to IR is needed for better
management of BCA/CM. In our laboratory, we have developed differentiation-enhanced combination PDT (cPDT), a
concept in which a pro-differentiating agent (methotrexate; vitamin D; or 5-fluorouracil, 5FU) is used as a neoadjuvant
prior to PDT. After using these neoadjuvants, levels of protoporphyrin IX (PpIX) were elevated in animal tumor models
of skin, prostate, and BCA, leading to better PDT efficacy. However, all the agents have toxicity issues. Here, we use a
nontoxic 5FU precursor called Capecitabine (CPBN) for cPDT. CBPN is a standard chemotherapeutic for metastatic
BCA, and is metabolized to 5FU specifically within tumor tissue. Murine (4T1) and human (MCF-7) BCA cell lines
were injected into breast fat pads of nude mice. After tumor nodules appeared, CPBN (400-600 mg/kg/day) was
administered by oral gavage for five days followed by intraperitoneal ALA administration on day 6. Mice were
sacrificed and tumors harvested. CPBN pretreatment led to a 4-fold elevation of PpIX levels in tumors, relative to
vehicle control. Not only did PpIX levels increase, but also PpIX distribution became more homogeneous after CPBN
pretreatment. In summary, the use of non-toxic CPBN as a neoadjuvant prior to PDT is a combination approach with
significant potential for translation into the clinic.