Systemic treatment of vulvar cancer

Abstract

Squamous cell carcinoma of the vulva is a rare disease, accounting for approximately 5% of cancers of the female genital tract. Standard therapy for early-stage vulvar cancer mainly comprises of surgery of the vulva and groins. In locally advanced or metastatic vulvar cancer, neoadjuvant or definitive chemoradiation is often considered as an alternative treatment option. Given its rarity, the level of evidence for different treatment modalities is poor and few clinical trials have been performed on this disease. Therefore indication criteria for systemic treatment in advanced stage vulvar cancer vary widely among countries and institutions. This review focuses on the different systemic treatment options for patients with locally advanced, recurrent or metastatic vulvar cancer, and highlights the need for an international multicenter approach to identify the most effective therapeutic options.

Keywords:

• chemotherapy
• metastatic
• neoadjuvant
• targeted treatment
• vulvar cancer

Financial & competing interests disclosure

S Mahner has received research support, honoraria and travel support from Roche, Astra Zeneca, MSD, PharmaMar, GSK, Janssen-Cilag, MEDAC, Debiopharm. V Mueller has received speaker honoraria from Amgen, Celgene, Eisai, GlaxoSmith Kline, Pierre-Fabre, Roche, Jannsen-Cilag. L Woelber has received research support, honoraria and travel support from MEDAC, MSD. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• In the last two decades, no improvement in survival could be achieved for locally advanced, recurrent or metastatic vulvar cancer.

• Neoadjuvant chemoradiation achieves high rates of resectability.

• Systemic therapy is a treatment option for patients that are otherwise only candidates for ultra-radical surgery.

• Due to small study populations and variation of inclusion criteria, determination of the best chemotherapy/radiation regimen with the least toxicity is difficult.

• Cisplatin or a combination of cisplatin and 5-fluorouracil (5-FU) are the most commonly used agents for chemoradiation.

• Neoadjuvant chemotherapy is a relatively new approach to improve operability while avoiding increased morbidity of radiation plus surgery.

• Erlotinib (a selective epidermal growth factor receptor (EGFR) inhibitor) treatment in primary, recurrent or metastatic vulvar squamous cell carcinoma (VSCC) showed promising results with an overall clinical benefit rate of 67.5% in a first controlled clinical Phase II trial. However, responses were short and toxicities significant.

• A key problem treating a rare disease like vulvar cancer is the lack of large randomized prospective multi-center clinical trials.