Vincristine project Kenya

 

Background

Vincristine is a type of chemotherapy that is often used in children with cancer. It is affordable, effective and widely available, which makes it attractive for use in low-income countries such as Kenya (1). Research has shown that children with cancer who are being treated in a low- or middle income country have lower survival rates compared to children in high-income countries (2, 3). This is due to multiple factors,  such as treatment abandonment or not starting treatment at all. Other possible causes are differences in ethnic and thus genetic background. It is well-known that ethnicity influences the metabolism of diverse medications. There is evidence that black children may metabolize chemotherapy such as vincristine faster than white children. In addition, black children appear to experience less side-effects of vincristine compared to white children (4-8). However, the downside of this seemingly positive finding, is most likely vincristine has a lower therapeutic effectiveness on cancer cells due to suboptimal exposure (1). The aim of the vincristine project in Kenya is to determine the optimal dose in black, Kenyan children with cancer. We will measure the vincristine blood concentrations at multiple time points during treatment, while simultaneously assessing the occurrence of side-effects. If there are no or little side-effects and the vincristine concentrations in the blood are too low, we want to increase the vincristine dosage. The overarching aim of this study is to contribute to the improvement of survival rates of Kenyan children with cancer.

 

Challenges
  • To perform reliable measurements of the vincristine concentration in blood. Currently, there is no laboratory in Kenya that can perform these measurements.

  • There is no treatment protocol specifically designed for Kenyan children with cancer that are treated with vincristine.

  • To develop a tailored treatment approach for each child: to determine the optimal dosage of vincristine, based on genetic differences.

  • Due to poverty there is a high rate of treatment abandonment.

  • Children often live far away from the hospital where they are treated.

 

Facts & figures
  • The chance of survival for a Kenyan child with cancer is 30%, whereas Dutch children have a 75% survival rate;

  • Almost all children with cancer can be included in this study, because most children receive vincristine as a part of their treatment.

  • All included children in this study will be treated in the Moi Teaching and Referral Hospital in Eldoret, Kenya.

  • We will start including the first children with cancer in 2021.

  • Project leader in Eldoret, Kenya is dr. Festus Njuguna (pediatrician).

  • Project leader in the Prinses Máxima Centre in the Netherlands is prof. Gertjan Kaspers (pediatrician-oncologist);

  • The vincristine project will be performed by drs. Aniek Uittenboogaard (physician-researcher), under direct supervision of drs. Mirjam van de Velde (postdoc).

 

Activities
  • To include Kenyan children with cancer in this study.

  • To measure the vincristine concentration in the blood.

  • To assess the presence of side-effects of vincristine.

  • To optimize the vincristine dosage based on these measurements.

  • To keep track of ‘events’: such as refractory disease, relapsed disease, or death of the patient.

 

Impact

The aim of this study is to lower the number of deaths due to cancer in children, by optimizing the dosage of vincristine. This information can be used for black children all over the world. This will help us close the gap between the survival rates of Kenyan and Dutch children with cancer.

Furthermore, this information is useful for the treatment of Dutch children as well. Possibly, they receive a dosage that could either be too high or too low. Optimizing their dosage will prevent under- and overtreatment with vincristine.

 

Literature list

1. Skiles JL, Chiang C, Li CH, Martin S, Smith EL, Olbara G, et al. CYP3A5 genotype and its impact on vincristine pharmacokinetics and development of neuropathy in Kenyan children with cancer. LID - 10.1002/pbc.26854 [doi]. Pediatr Blood Cancer. 2018;65(3):e26854.

2. Jemal A, Thomas A, Murray T, Thun M. Cancer statistics, 2002. CA Cancer J Clin. 2002;52(1):23-47.

3. Pollock BH, DeBaun MR, Camitta BM, Shuster JJ, Ravindranath Y, Pullen DJ, et al. Racial differences in the survival of childhood B-precursor acute lymphoblastic leukemia: a Pediatric Oncology Group Study. J Clin Oncol. 2000;18(4):813-23.

4. van de Velde ME, Kaspers GL, Abbink FCH, Wilhelm AJ, Ket JCF, van den Berg MH. Vincristine-induced peripheral neuropathy in children with cancer: A systematic review. Crit Rev Oncol Hematol. 2017;114:114-30.

5. Anghelescu DL, Faughnan LG, Jeha S, Relling MV, Hinds PS, Sandlund JT, et al. Neuropathic pain during treatment for childhood acute lymphoblastic leukemia. Pediatric Blood and Cancer. 2011;57(7):1147-53.

6. Diouf B, Crews KR, Lew G, Pei D, Cheng C, Bao J, et al. Association of an inherited genetic variant with vincristine-related peripheral neuropathy in children with acute lymphoblastic leukemia. JAMA - Journal of the American Medical Association. 2015;313(8):815-23.

7. Kishi S, Cheng C, French D, Pei D, Das S, Cook EH, et al. Ancestry and pharmacogenetics of antileukemic drug toxicity. Blood. 2007;109(10):4151-7.

8. Renbarger JL, McCammack KC, Rouse CE, Hall SD. Effect of race on vincristine-associated neurotoxicity in pediatric acute lymphoblastic leukemia patients. Pediatr Blood Cancer. 2008;50(4):769-71.

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