Saving the Children — Improving Childhood Cancer Treatment in Developing Countries Saving the Children — Improving Childhood Cancer Treatment
in Developing Countries
Raul C. Ribeiro, M.D., and Ching-Hon Pui, M.D.
Unprecedented gains have been made in the cure rus infection and AIDS remain a critical health pri-rates for childhood cancer during the past four de- ority in sub-Saharan Africa, cancer is emerging ascades. This progress reflects steady improvement in a major cause of childhood death in developingtreatment protocols, a multidisciplinary approach regions of Asia, South and Central America,to patient care, adequate hospital infrastructure, and northwest Africa, and the Middle East, as a resultpsychosocial and economic support for affected of reduced mortality from preventable infectiousfamilies. Perhaps the greatest success has been the diseases.3 For example, in 1960, the rate of death80 percent cure rate among children with acute lym- among infants in China was 150 per 1000 live births;phoblastic leukemia who are treated in a modern among children under five years of age, the deathcenter. Most of these survivors have long, produc- rate was 225 per 1000 live births. By 2002, the ratestive lives, are well integrated into their communities, had decreased to 31 per 1000 and 39 per 1000, re-and make substantial contributions to society.1 But spectively. As the population of Chinese childrenthis story of medical achievement is tempered by nears 300 million, a conservative projection ofthe harsh reality that more than 60 percent of the 45,000 new cases of pediatric cancer each year canworld’s children with cancer have little or no access be made.
to effective therapy, and their survival rates are pre- At the Shanghai Children’s Medical Center, dictably inferior to those in countries with advanced which serves the only Chinese city in which healthhealth care systems. The geographic inequality in insurance for catastrophic diseases is offered, 234cancer treatment poses challenges that have only children with acute lymphoblastic leukemia werebegun to be addressed.2,3 admitted for treatment between October 1998 and Perhaps the most compelling case to be made June 2003. According to Dr. J.Y. Tang of the medi- against investing in better cancer treatment for cal center, therapy for 66 of these children (most ofchildren in poor countries is that millions of deaths whom did not live in Shanghai) had to be aban-may be prevented by focusing instead on relatively doned, apparently for financial reasons, and anoth-inexpensive strategies for combating infectious dis- er 52 children died of leukemia or treatment-relatedeases. Indeed, the World Health Organization and complications, leaving only 116 in continuous com-many international charities have committed their plete remission. This problem is much worse else-resources to reducing mortality from infectious dis- where in the country, especially in rural areas: onlyeases by two thirds during the next decade. Not sur- about 10 percent of Chinese children under 14 yearsprisingly, noncommunicable diseases and chronic of age who have acute leukemia receive protocol-childhood disorders are not among the priorities of based therapy, according to Dr. L.J. Gu, also of thethese organizations. Although the marshaling of re- Shanghai center.
sources to fight infectious diseases clearly has the What, if anything, can be done to bring the ben- potential to save the most children in developing efits of modern cancer treatment to more children?countries, we would argue that alternative support The most immediate and substantial results willmechanisms are also needed to ensure wider ac- probably come from expanded access to treatment,cess to effective cancer treatment. This argument the elimination of reasons for abandoning treat-is not grounded solely in humanitarian consider- ment, and better control of complications of infec-ations; it also addresses the rapidly changing pro- tions. Possible approaches to achieving these goalsfile of causes of illness and death among children are admirably covered in the recent book Cancer inin countries with limited resources.
Developing Countries: The Great Challenge for Oncology in Although pediatric human immunodeficiency vi- the 21st Century. One strategy, described in the chap- ters by Masera et al. and Cavalli, emphasizes a part- Dr. Ribeiro is director of the International Outreach Pro- nership (“twinning”) between institutions in de- gram and Dr. Pui is director of the Leukemia/Lymphoma veloped countries and those in underdeveloped Division at St. Jude Children’s Research Hospital inMemphis, Tenn. Dr. Pui is also a clinical research profes- countries, an approach that seems most likely to Downloaded from on June 21, 2005 . For personal use only. No other uses without permission. Copyright 2005 Massachusetts Medical Society. All rights reserved. Saving the Children — Improving Childhood Cancer Treatment in Developing Countries Percentage of Patients
Death from
Event-free Survival
of Treatment
Toxic Effects
Frequency of Treatment Failure during the First Year after Diagnosis and Two-Year Event-free Survival Rates
among Children with Acute Lymphoblastic Leukemia Treated in a Public Hospital in Recife, Brazil.

Before the establishment of a twinning program with St. Jude Children’s Research Hospital in 1994, the abandonment of treatment and the rate of relapse were major causes of failure. With the introductions of intensive, protocol-based che-motherapy and a private community support group that provides transportation, housing, and job opportunities for pa-tients and their parents, the relapse rate has decreased markedly, and the rate of treatment abandonment has decreased from 16 percent to less than 1 percent. The use of more aggressive therapy has resulted in more deaths from infection and hemorrhage, but refinements in patient care have begun to ameliorate these complications. The most recent analy-sis of event-free survival shows rates similar to those in some highly developed countries. There are no data for 1990 through 1993 because the pediatric oncology unit at the Recife Hospital was closed during that period. An overlap in re-porting periods occurred because the study protocol changed on April 1, 1997. Examples of the twinning approach to childhood their expertise with other oncologists in the devel- cancer treatment have been in place in Central and oping regions of Latin America, by developing jointSouth America, northwest Africa, and southeast treatment protocols and consulting about problemsAsia for as long as 10 years.3,4 These programs have in the management of childhood cancer.
reduced the rates of abandonment of treatment, re- Can twinning be effective in countries that lack lapse, and death due to toxic effects of treatment even rudimentary health care systems? We believe(see graph), and the investments they have attract- that a low level of development does not pose an in-ed have led to improvements in access to treatment surmountable obstacle to a productive partnership.
and hospital infrastructure.
In parts of Africa, for example, it may be possible to Briefly, twinning fosters interactions between cure children of Burkitt’s lymphoma by treating public hospitals in developing countries and estab- them with cyclophosphamide alone, and there islished cancer treatment centers, with the goal of evidence from Malawi that even a simplified twin-improving survival rates among children with can- ning program can save lives.5 Thus, a modifiedcer. The best results have been obtained when local program concentrating on education, training, andoncologists were recruited as program directors and the treatment of the most responsive cancers couldasked to promote the idea of a strong pediatric on- be quite effective.
cology unit among their peers and coordinate the Most progress in pediatric cancer treatment has training of providers. Although at first the partner been stimulated by research involving children ininstitution in the more affluent country may subsi- Western countries. Since the susceptibility to anddize the costs of treatment, these and other expens- pathogenesis of cancer are heavily influenced byes are eventually met with funds raised by charitable genetic background, environmental exposure, andgroups in the community. Such alliances have gen- lifestyle, we must broaden research to include cas-erated sufficient momentum to allow some hospi- es in developing countries. It will be easier to do sotals in Central and South America to begin sharing if the development of pediatric-cancer units in poor Downloaded from on June 21, 2005 . For personal use only. No other uses without permission. Copyright 2005 Massachusetts Medical Society. All rights reserved. Saving the Children — Improving Childhood Cancer Treatment in Developing Countries velopment of curative treatment for children withcancer is a benchmark for medical progress, andsuch treatment must not be sequestered within theborders of a few countries. The strategy we describeis only a start, but it could ignite a spirit of achieve-ment that may ultimately reach even the least privi-leged nations.
Cancer in Developing Countries: The Great Challenge for Oncology inthe 21st Century, edited by S. Tanneberger, F. Cavalli, and F. Pannu-ti, was published by Zuckschwerdt, Munich, 2004.
Pui CH, Cheng C, Leung W, et al. Extended follow-up of long- term survivors of childhood acute lymphoblastic leukemia.
N Engl J Med 2003;349:640-9. [Erratum, N Engl J Med 2003;349: Pui CH, Schrappe M, Masera G, et al. Ponte di Legno Work- ing Group: statement on the right of children with leukemia to A Patient with Acute Lymphoblastic Leukemia at the Shanghai Children’s
have full access to essential treatment and report on the Sixth In- Medical Center.
ternational Childhood Acute Lymphoblastic Leukemia Workshop.
Pui CH, Ribeiro RC. International collaboration on childhood leukemia. Int J Hematol 2003;78:383-9.
countries leads to the evolution of international 4. Howard SC, Pedrosa M, Lins M, et al. Establishment of a pe-
diatric oncology program and outcomes of childhood acute lym- banks of cells and tissue and of cancer registries phoblastic leukemia in a resource-poor area. JAMA 2004;291: that collect long-term follow-up data.
It has been said that if we are to preserve civiliza- 5. Kazembe P, Hesseling PB, Griffin BE, Lampert I, Wessels G.
Long term survival of children with Burkitt lymphoma in Malawi tion, we must make certain its benefits are avail- after cyclophosphamide monotherapy. Med Pediatr Oncol 2003; able to the many, not reserved for the few. The de- 40:23-5.
Gag Clauses in Clinical-Trial Agreements
Robert Steinbrook, M.D.
Related article, page 2202
Gag clauses in clinical-trial agreements prevent in- sible author of a study state in writing that he or shevestigators from examining the data independently accepted full responsibility for the conduct of the tri-or submitting a manuscript for publication without al, had access to the data, and controlled the deci-first obtaining the consent of the sponsor. Sponsors sion to publish.2 Subsequently, researchers at Dukewith a financial interest in the outcome of clinical University (Durham, N.C.) surveyed the provisionsresearch can suppress negative results. They can in clinical-trial agreements between medicalalso interfere with the publication of unfavorable schools and industry sponsors and found that “aca-data on safety, as it was recently alleged that Merck demic institutions routinely engage in industry-officials did in the company-sponsored “Advan- sponsored research that fails to adhere to ICMJEtage” study of rofecoxib for the treatment of os- guidelines regarding trial design, access to data, andteoarthritis published in 2003.1 Some of the hidden publication rights.”3 In response, the researchersdata, like those related to cyclooxygenase-2 inhibi- and others proposed that there should be standardtors and the use of antidepressants in children, may contract provisions for industry-sponsored researcheventually become public, but other studies are nev- conducted at academic medical centers.4er reported.
In 2005, has anything changed? The short an- In 2001, the International Committee of Medical swer is no. Dr. Robert M. Califf, the director of the Journal Editors (ICMJE), which then represented 11 Duke Clinical Research Institute, noted recently,general medical journals, including the New England “I do not see any evidence that the average contractJournal of Medicine, began to require that the respon- of a site participating in a multicenter study is any better now than when we wrote the article.” Accord- Dr. Steinbrook is a national correspondent for the Journal.
ing to Dr. Steven E. Nissen, the director of the Cleve- Downloaded from on June 21, 2005 . For personal use only. No other uses without permission. Copyright 2005 Massachusetts Medical Society. All rights reserved.


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