Background and purpose: Cervical cancer is the fourth commonest cancer in women in the world with the highest regional incidence and mortality seen in Southern, Eastern and Western Africa. It is the commonest cause of cancer morbidity and mortality among Zimbabwean women. Most patients present with locally advanced disease that is no longer amenable to surgery. Definitive concurrent chemoradiation (CCRT), which is the use of external beam radiotherapy (EBRT) and weekly cisplatin, includes use of intracavitary brachytherapy, as the standard treatment. In the setting of this study, cobalt-60 (Co60)-based high dose rate brachytherapy (HDR-BT) has been in use since 2013. This study sought to review practices pertaining to use of brachytherapy in Zimbabwe, including timing with external beam radiotherapy, adverse effects and patient outcomes. Methods: A retrospective analysis of data from records of patients with histologically confirmed cervical cancer treated with HDR-BT at the main radiotherapy centre in Zimbabwe from January 2013 to December 2014 was done. Outcome measures were local control, overall survival as well as gastro-intestinal and genito-urinary toxicity. Results: A total of 226 patients were treated with HDR-BT during the study period, with a 97% treatment completion rate. All patients received between 45-50Gy of pelvic EBRT. Seventy-four percent received concurrent platinum-based chemotherapy. In 52% of the patients, HDR-BT was started when they were still receiving EBRT. The commonest fractionation schedule used was the 7Gy × 3 fractions, once a week (87%). Clinical complete tumour response was achieved in 75% at 6 weeks post treatment, 23% had partial response. Follow-up rates at 1 year and 2 years were 40 and 19% respectively. Disease free survival at 1 year and 2 years was 94 and 95% respectively. Vaginal stenosis was the commonest toxicity recorded, high incidence noted with increasing age. Four patients developed vesico-vaginal fistulae and two patients had rectovaginal fistulae. Conclusion: One hundred and seventeen patients patients started HDR-BT during EBRT course, with a treatment completion rate of 97%. The overall treatment duration was within 56 days in the majority of patients. Early local tumour control was similar for all the HDR-BT fractionation regimes used in the study, with a high rate (75%) of complete clinical response at 6 weeks post-treatment. Prospective studies to evaluate early and long-term outcomes of HDR-BT in our setting are recommended.
27 January 2023 in British Journal of Clinical Pharmacology
O(on behalf of Consortium for Genomics and Therapeutics in Africa (CGTA)
on behalf of Consortium for Genomics and Therapeutics in Africa (CGTA)
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Fluoropyrimidines are commonly used in the treatment of colorectal cancer. They are, however, associated with adverse events (AEs), of which gastrointestinal, myelosuppression and palmar-plantar erythrodysesthesia are the most common. Clinical guidelines are used for fluoropyrimidine dosing based on dihydropyrimidine dehydrogenase (DPYD) genetic polymorphism and have been shown to reduce these AEs in patients of European ancestry. This study aimed to evaluate, for the first time, the clinical applicability of these guidelines in a cohort of cancer patients on fluoropyrimidine standard of care treatment in Zimbabwe. DNA was extracted from whole blood and used for DPYD genotyping. Adverse events were monitored for six months using the Common Terminology Criteria for AEs (CTCAE) v.5.0. None of the 150 genotyped patients was a carrier of any of the pathogenic variants (DPYD*2A, DPYD*13, rs67376798, or rs75017182). However, severe AEs were high (36%) compared to those reported in the literature from other populations. There was a statistically significant association between BSA (p = 0.0074) and BMI (p = 0.0001) with severe global AEs. This study has shown the absence of the currently known actionable DPYD variants in the Zimbabwean cancer patient cohort. Therefore, the current pathogenic variants in the guidelines might not be feasible for all populations hence the call for modification of the current DPYD guidelines to include minority populations for the benefit of all diverse patients.
Trends in gastrointestinal cancer burden in Zimbabwe: 10-year retrospective study 2009–2018 Tinashe Adrian Mazhindu1,2,3, Ntokozo Ndlovu1,2, Margaret Borok
3 April 2026 in Clinical Pharmacology & Therapeutics
The World Health Organization Model Essential Medicines List and African national essential medicines lists (EMLs) detail drugs intended to be consistently available within national health systems, thereby supporting clinicians and pharmacists in making evidence‐based treatment decisions. At present, these EMLs do not account for pharmacogenomics, despite known drug‐gene interactions and the considerable genetic diversity found throughout Africa. In the absence of pharmacogenomic considerations, the medicines lead to sub‐optimal treatment outcomes, especially across a continent such as Africa which represents more genetic variation that the rest of the world combined. Herein, we review EMLs from the WHO, and from 52 African countries, highlighting systemic medicines for which actionable pharmacogenomic‐biomarker testing recommendations exist. Furthermore, we assess the feasibility of PGx‐guided dosing in eight African countries by examining the availability of registered drug formulations that facilitate dose adjustment. The 2023 WHO EML comprised 447 unique systemic medicines, with 58 (13%) categorized as medicines with actionable pharmacogenomic biomarkers. African country EMLs collectively featured 774 such medicines, with an average of 294 per country (range: 125–465). On average, for each country one in every eight medicines in the Essential Medicines List was associated with established pharmacogenomic guidance. PGx recommendation. Cumulatively in African EMLS the most frequent drug classes with this designation are anti‐infectives (25.6%), immunomodulators/antineoplastics (16.7%), and medicines for mental and behavioral disorders (14.1%). Analysis of eight African countries determined that implementability ranged from 75% to 96% based on product formulation and strength availability to enable drug or dose modification. We provide data that contributes towards a foundation of increasing evidence showing that integrating pharmacogenomic knowledge into the selection processes for essential medicines and ensuring the availability of appropriate drug formulations can enhance treatment safety and efficacy across Africa.