Metronomic chemotherapy and treatment selection in metastatic breast cancer

Abstract

Treatment for metastatic breast cancer (MBC) aims to relieve cancer-related symptoms and prolong survival without causing excessive toxicity. The cornerstone is sequential systemic oncologic therapies throughout most of the patient´s remaining life. Treatment selection is complex, as multiple options exist, including endocrine therapy, chemotherapy, and targeted agents, and is guided by breast cancer subtype, patient related factors and preferences. Traditionally, chemotherapy has been given at the maximum tolerated dose but in the early 2000s, metronomic chemotherapy (MCT), using continuous low-dose oral administration, emerged as an alternative treatment strategy.

This thesis investigated the role of MCT with capecitabine and cyclophosphamide in MBC, and treatment selection in late-line. In paper I, MCT was retrospectively evaluated, demonstrating a median time on treatment of nine months, with limited toxicity. In Paper II, a clinical phase II trial, MCT demonstrated a clinical benefit rate of 45% (complete or partial response, or stable disease for more than 24 weeks) with preserved quality of life. Paper III was a qualitative study where patients described MCT as convenient, helping them maintain a normal life, while also expressing concerns about the potentially insufficient dosing. Paper IV was a qualitative study interpreting how oncologists approach late-line treatment selection as active stakeholders in a value-driven process. In their view, decisions were ideally made through collaborative dialogue with patients, but they were also prepared to use their professional knowledge to decide or allow patient influence, while continuously also seeking collegial support to maintain integrity.

In conclusion, this thesis suggests that MCT can provide clinical benefit and help patients maintain a life close to normal despite living with MBC. However, rather than using the term MCT as an isolated concept, chemotherapies should be investigated individually by comparing the minimally effective dose with the maximum tolerated dose. Further, it is essential for oncologists to articulate the rationale behind their treatment recommendation to patients, to foster person-centred care.