The Use of Localised Vaginal Drug Delivery as Part of a Neoadjuvant Chemotherapy Strategy in the Treatment of Cervical Cancer

Christopher McConville

DOI: https://doi.org/10.17140/goroj-2-106 · Published 2015-03-03 · Licence: https://creativecommons.org/licenses/by/4.0 · © 2015 The Author(s)

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Opinion The Use of Localised Vaginal Drug Delivery * *Corresponding author as Part of a Neoadjuvant Chemotherapy Christopher McConville, PhD Senior Lecturer Pharmaceutics Strategy in the Treatment of Cervical Faculty of Science and Engineering School of Pharmacy University of Wolverhampton Cancer Wolverhampton, WV1 1LY, UK Tel. 01902 322615 * E-mail: c.mcconville@wlv.ac.uk Christopher McConville* Volume 2 : Issue 1 Senior Lecturer Pharmaceutics, Faculty of Science and Engineering, School of Pharmacy, University of Wolverhampton, Wolverhampton, WV1 1LY, UK Article Ref. #: 1000GOROJ2106 Article History Cervical cancer is the third most prevalent cancer in women globally, with 529,000 th Received: February 13th, 2015 diagnosis and 275,000 deaths each year. It is especially prevalent in developing countries where nd Accepted: March 2nd, 2015 approximately 85% of cases arise due to the lack of cervical cancer prevention and control pro- rd Published: March 3rd, 2015 grams. In developed countries, where women have access to resources capable of detecting and treating precancerous lesions, the number of cases is reduced by approximately 80%.1 Cervical cancer can be characterised, depending on how far it has spread, from stage 0 (precancerous), Citation also called Cervical Intraepithelial Neoplasia (CIN), where abnormal cells are found in the McConville C. The use of localised vaginal drug delivery as part of a neo- innermost lining of the cervix and have the potential to become cancerous, through to stage adjuvant chemotherapy strategy in 4, where the cancer has spread to the bladder, rectum or other parts of the body, such as the the treatment of cervical cancer. Gy- lungs. In developed countries, there are currently two methods used to prevent cervical cancer necol Obstet Res Open J. 2015; 2(1): from developing to an advanced stage: (1) the distribution of HPV vaccines that are mainly 26-28. doi: 10.17140/GOROJ-2-106 directed against HPV types 16 and 18 and (2) screening methods, such as Papanicolaou test (Pap smear), which involves the collection of exfoliated cells from the cervix, which are then examined for cellular abnormalities. This enables identification of CIN before they begin to develop into cervical cancer.3 Strategies for cervical cancer treatment will depend on the women’s general health as well as the type, stage and grade of the cancer and usually involve a combination of surgery, 4,5 chemotherapy and radiotherapy.4,5 Increasing numbers of women of reproductive age are being diagnosed with cervical cancer, with approximately 15% of all cervical cancers and 45% of stage IB cancers treated using surgery occurring in women under the age of 406 The two main surgical procedures in fertility sparing treatment are Vaginal Radical Trachelectomy (VRT) and Abdominal Radical Trachelectomy (ART). A review of fertility sparing surgery by Rob et al. demonstrated that radical trachelectomy is safe with similar risk of recurrence to that of radical hysterectomy in selected cases of small volume tumours measuring less than 2 cm in diameter.7 Fertility sparing treatment is only offered to those women that meet a certain criteria such as a diagnosis of early stage cervical cancer where the tumour is limited to the cervix with no evidence of pelvic lymph node metastasis and/or other distant metastasis and a tumour size of less than 2 cm.8 Adherence to these criteria is important in reducing the risk of recurrence, 9-11 which is significantly higher in tumours greater than 2 cm.9-11 The recurrence rate in women with tumours greater than 2 cm is 20.8% after VRT and 20% after ART compared to 2.9% and 1.9% respectively in tumours less than 2 cm.7 Copyright ©2015 McConville C. This is an Systemic administration of Neoadjuvant chemotherapy (NAC) can be used to down- open access article distributed un- stage the tumour before fertility sparing surgery, thus decreasing the tumour volume and al- der the Creative Commons Attribu- tion 4.0 International License (CC lowing for a much smaller tumour to be removed. A review of three clinical trials investigating BY 4.0), which permits unrestricted NAC and fertility sparring surgery involving 33 women (24 with tumours greater than 2 cm) use, distribution, and reproduction demonstrated that 26 of the women had their fertility spared, which resulted in 18 conceptions in any medium, provided the origi- and 16 deliveries, 4 of which were premature, while only 1 of the women had a recurrence nal work is properly cited.

of the cancer.7 The response rate of advanced cervical cancers to NAC has been shown to be 12-14 between 60 and 95% and a recent Cochrane review on NAC improve the patients overall quality of life both during and after plus surgery (radical hysterectomy and radical trachelectomy) treatment allowing for the patient to recover much quicker re- versus surgery alone demonstrated that both the overall survival sulting in reduced hospital presentations and admissions, which and progression-free survival where significantly improved, could have a cost saving effect on the global healthcare system.

while local recurrence was reduced with the use of NAC.15 How- With an increase in the number of NAC clinical studies being ever, parenteral administration of chemotherapeutic drugs has an performed, albeit using systemic delivery of chemotherapeutic adverse effect on patients due to systemic side effects. Localised drugs, the benefits of NAC in conjunction with fertility sparring delivery of chemotherapeutic drugs offers a number of advan- surgery and standard surgery are being recognised. Therefore, tages over parenteral administration such as direct delivery to within the next five to ten years NAC in conjunction with either the site of action resulting in a lower dose being required as well fertility sparing surgery or a standard treatment regimen will be as a reduction in systemic side effects and increased drug stabil- the main cervical cancer treatment protocol, especially for those ity as it remains in the delivery device until released.16 The loca- women who have a tumour size greater than 2 cm, to both pre- tion of the cervix makes it easily accessible through the vagina serve fertility and reduce recurrence. This will lead to the re- and allows for the non-invasive implantation of a localised drug alisation that when it comes to the treatment of cervical cancer delivery device adjacent to the cancerous tissue either before re- localised drug delivery is much more beneficial than systemic section, to reduce tumour size, or after resection to reduce the drug delivery, due to an improved quality of life for the patient risk of recurrence.

during treatment, faster recovery times, reduced recurrence and better patient compliance. Therefore, over the next 5 to 10 years The vagina has been used to deliver drugs for a range of there will be a rise in the number of NAC clinical trials which clinical and research applications, including contraception, vagi- compare localised delivery to systemic delivery in reducing tu- nal infections and HIV prevention, with many different vagi- mour size, which will lead to an increase in the development, nal formulations such as gels, creams, pessaries, suppositories, testing and regulatory approval of vaginal dosage forms for the 17-23 rings, films and tablets available. Furthermore, a number of localised delivery of chemotherapeutic drugs to the cervix.

these delivery systems have already been investigated for the 24-30 localised delivery of chemotherapeutic drugs to the cervix.

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