ES5-3: Novel Approaches to Breast Cancer Management in Low-Income Countries.
Authors: Kerr DJ 
Published: June 2012

Abstract
There is clear evidence that the global burden of cancer is increasingly affecting low and middle - income countries, effectively those nations who have least health infrastructure to deal with complex diseases like cancer. A new approach to cancer therapy is required that combines efficacy, reduced side effects, cost-effectiveness with a delivery mechanism that does not rely on access to distant and expensive regional cancer centres. To this end we propose to develop a combination oral chemotherapy formulation which is likely to offer a clinically useful advantage to patients suffering from breast cancer For almost half a century, systemic therapy of cancer has been dominated by the use of cytotoxic chemotherapeutics. Most of these drugs are DNA damaging agents or microtubule inhibitors that are designed to inhibit or kill rapidly dividing cells, often administered in single doses or short courses of therapy at the highest doses possible, with prolonged breaks (generally of 2–3 weeks in duration) between successive cycles of therapy. A reappraisal of the optimal way of administering chemotherapy is underway. Instead of using short bursts of toxic chemotherapy interspersed with long breaks to allow recovery from the harmful side effects, there is now a shift in thinking towards the view that more chronic or decelerated schedules of drug administration using much smaller individual doses than the MTD may be more effective — not only in terms of reducing certain toxicities, but perhaps also improving anti-tumour efficacy with an additional anti-endothelial cell effect, so-called ‘metronomic’ chemotherapy. We propose development of a flat dose, combination, oral chemotherapy formulation which will contain the following classes of antineoplastic agents, which have been shown to have activity in breast cancer. Fluoropyrimidines eg Capecitabine; Alkylating Agents eg Cyclophosphamide; Antiemetics eg Metoclopramide; administered continuously at doses inducing Grade 1 toxicity.
The drug doses will be carefully selected to provide moderately effective cancer control with reduced toxicity profiles. The clinical development pathway will be conducted in India and SubSaharan Africa with a view to providing a managed package of care which will allow delivery of the MetroPill to women with breast cancer in rural and minor urban settings rather than the regional cancer centres. We will train a cohort of district general hospital doctors/nurses to monitor and deliver the MetroPill, supported by a teaching package app and mobile phone technology to provide symptom support for patients. A phase 1 feasibility and pharmacokinetic study will be performed in 20–30 patients followed by single arm Phase 2 studies(n=40 patients) in breast cancer patients, which will report response rates, progression free survival and quality of life as a prelude to phase 3 trials. We believe that this is the sort of lateral approach we must consider if we are to take elements of cancer therapy to those regions which lie beyond the shadow of conventional cancer centres.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr ES5-3.