Eduardo Gharzouzi , MD, surgical oncologist at the Instituto de Cancerología, Guatemala City and one of the 2015 Global Health Week speakers
In 2012, there were an estimated 14.2 million cases of cancer worldwide. More than half of this cancer burden comes from developing countries.
By 2030, 60% of new cancer cases and 70% of cancer deaths are expected to be in the least developed countries. Yet, despite this growing cancer burden, less than 7% of global cancer resources were allocated to developing countries. (1)
Radiotherapy is an enormous problem. Unfortunately, only 20-25% of patients can access radiotherapy treatment today. In developing countries, the only centers that may offer radiotherapy are located in the more important cities; often in only the capital city. Most developing countries can only afford radiotherapy with telecobalt (Co60) machines that for the most part are extremely old machines. (3) Most developing countries have very low ratios of machines per population, often one machine for several million people, versus a ratio of one machine per 250,000 inhabitants, which is typical of most developed countries. In general there is a lack of preventive maintenance, so machine down-time is usually high. There is also a lack of well-trained staff, which translates in underutilization, and inappropriate utilization of even the existing scarce radiotherapy facilities in developing countries. (4) The waiting list for this enormous population of cancer patients needing radiotherapy with not enough machines to treat them, usually translates to as much as 6 to 12 months delay in treatment; time in which cancers only do one thing: Grow!
The cost of chemotherapy is another factor affecting cancer care in developing countries. Most developing countries have high rates of poverty and extreme poverty, with family incomes ranging from $1 to $5 a day. Many of these families are large; having four or more children is not uncommon at all. You can add to this, cultural issues such as “machista” husbands leaving their wives with cervical or breast cancer, because they are not “whole” women anymore, since the disease has affected the organs that “make” her a woman. These women are then left on their own with 4 or 5 children to provide for.
How is a breast cancer patient, under these circumstances, supposed to pay for the neoadjuvant chemotherapy she needs, and later for her mastectomy, and later on for radiotherapy and hormone therapy? The cheapest chemotherapy regimen (with generic drugs) she will find is no less than $1,350 (5FU+Adriamicin+Cyclophosphamide x 6). Forget about taxanes, and don’t even mention targeted therapy. At our Institution, more than 60% of our patients never begin or never finish their neoadjuvant treatment. We can just assume that they go home and wait for a long painful death.
If you google “standard of care,” the first definition from Wikipedia you will find is: A medical treatment guideline, which can be general or specific. It specifies appropriate treatment based on scientific evidence and collaboration between medical professionals involved in the treatment of a given condition. (5) In developing countries, this condition involves a lot more than just a bunch of cells growing and spreading out of control. How appropriate can this “standard” treatment be, if 60-70% cannot have access to it?
Treatment protocols and equipment modeled on the best-developed countries can seldom be applied directly to developing countries, due to all these reasons. So where standard therapy is either not available or difficult to reproduce, it is highly desirable to have treatment options with potential to save lives that otherwise would be lost due to lack of treatment. Here are two examples:
For our breast cancer patient with locally advanced disease mentioned above, neoadjuvant hormone therapy (NHT) can be a great alternative. Hormone receptor positive (HR+) breast cancer is quite sensible to NHT. Almost 70% of all breast cancers are HR+. Objective response rates for neoadjuvant Tamoxifen (TMX) have been reported of up to 40%. (6) Aromatase Inhibitors do even better, with over 60% objective response rates. (7) Costs of tamoxifen are very cheap. Four months of treatment will cost around $150 in Guatemala. This treatment has the advantage that tumor response can be assessed as soon as 2 to 4 weeks into treatment through KI-67 suppression measurements. If this proliferation marker is suppressed to less than 10% expression, the tumor is considered hormone sensitive. If it is not, the patient can be switched immediately to chemotherapy. (6) This means that for non-responders the time delay for receiving “standard” NACT would be only 2 to 4 weeks, which, by all standards, is quite acceptable. In a small study that included 32 HR+ breast cancer patients, we saw a 46.9% response rate (15 patients) by KI-67 with neoadjuvant TMX. Fourteen continued 4 months of treatment, and later had a mastectomy done (6.7% drop out rate). In contrast, of the 17 non-responders who went on to receive conventional chemotherapy, 23.5% did not receive or did not finish their treatment. Responders saved on average $1,165, which is money most of them used for their adjuvant TMX and radiotherapy (not published).
For locally advanced cervical cancer, a patient could wait as much as 6 to 12 months for her “standard” chemo-radiotherapy. Several studies have shown that “radiation-sparing” treatments, such as NACT followed by radical surgery can be as good as chemo-radiotherapy. Response rates vary from 47-88% depending on the combination of drugs used. (8) In an on-going study at our institution on Stage IIB cervical cancer patients that receive NACT based on relatively cheap drugs (cisplatinum+5FU: $145/cycle), 20 of 47 patients (42.6%) have shown an objective response rate, and have gone on to radical hysterectomy. Of these 20, five (25%) had a complete pathological response. Adjuvant radiotherapy was considered necessary only for 5 patients (25%). At an average follow-up of 14.8 months, none of these patients has recurred so far.
We cannot agree more with this statement from the Global Health Council Report on the Cancer Advocacy and Learning Initiative: “Countries need to develop programs and guidelines that are more efficient for their disease burden and resources, rather than focusing on programs that have the best and latest technologies. Prevention (and treatment) plans need to focus on what is feasible and realistic in each country and region, including training needs. These plans also need to develop a strategy for action.” (9)
Most governments in developing countries invest very little on health care, often assigning less than 2% of their national budget to their health ministries. Even worse, chronic diseases like cancer never get the attention they deserve. Prevention strategies are basically non-existing in developing countries. Sadly, we don’t expect this to change any time soon. So it is up to us in the trenches to find viable alternatives of treatment for our growing number of cancer patients, and establish, through our own research, what “standard of care” should be.
(1) Excerpt From: Bernard W. Stewart; Christopher P. Wild. “World Cancer Report 2014.”, IARC Publication, 2014. WHO Press
(2) Goss PE et al. Planning cancer control in Latin America and the Caribbean. Lancet Oncol 2013; 14: 391–436
(3) Bhadrasain V. Radiotherapy for Developing Countries. J Can Res Ther 2005;1:7-8
(4) Zubizarreta EH, Pointevin A, Levin CV. Overview of radiotherapy resources in Latin America: a survey by the International Atomic Energy Agency (IAEA). Radiother Oncol 2004; 73:97-100.
(6) Charehbili A, Fontein DB, Kroep JR et al. Neoadjuvant Hormonal Therapy for Endocrine Sensitive Breast Cancer: A Systematic Review. Cancer Treat Rev 2014;40(1):86-92
(7) Ellis MJ, Suman VJ, Hoog J et al. Randomized Phase II Neoadjuvant Comparison Between Letrozole, Anastrozole, and Exemestane for Postmenopausal Women With Estrogen Receptor–Rich Stage 2 to 3 Breast Cancer: Clinical and Biomarker Outcomes and Predictive Value of the Baseline PAM50-Based Intrinsic Subtype—ACOSOG Z1031. J Clin Oncol. 2011;29(17):2342-9
(8) NACCCMA Collaboration. Neoadjuvant Chemotherapy for Locally Advanced Cervix Cancer. Cochrane Database Syst Rev. 2004;(2):CD001774
(9) A Global Health Council Report on the Cancer Advocacy and Learning Initiative. The Burden of Cancer in Developing Countries. June, 2010. http://issuu.com/globalhealthcouncil/docs/rr_2010_cancer/1?e=3822300/5986553