The Need for Improvement of the Treatment of Advanced and Metastatic Cervical Cancer, the Rationale for Combined Chemo-Immunotherapy
Helene van Meir, Gemma G. Kenter, Jacobus Burggraaf, Judith R. Kroep, Marij J.P. Welters, Cornelis J.M. Melief, Sjoerd H. van der Burg and Mariette I.E. van Poelgeest
Affiliation: Department of Gynecology, Leiden University Medical Center, Leiden, the Netherlands.
The prognosis of patients with metastatic cervical cancer is poor with a median survival of 8-13 months. Despite the potency
of chemotherapeutic drugs, this treatment is rarely curative and should be considered palliative only. The last decades, targeted therapies
such as immunotherapy have emerged as an attractive option for the treatment of these patients. Immunotherapy can consist of different
modalities such as monoclonal antibodies, adoptive lymphocyte transfer and vaccines, which all are intended to augment the antitumor
immune responses in cancer patients. The available evidence indicates that both active and adoptive immunotherapeutical strategies are
quite effective against small tumor burdens, but are usually insufficient to eradicate the disease in patients with advanced stages of
different kinds of cancer, despite strong induction of tumor-specific immune responses. Although chemotherapy and immunotherapy
have not shown to be curative as single modalities, accumulating evidence suggests that combinations of these treatments hold potential
for improved clinical outcomes in advanced stages of cancer. Therefore, the combination of chemotherapy and immunotherapy is no
longer considered incompatible, because of the emerging insight that certain chemotherapy-based cancer treatments may activate the
immune system against the tumor through several molecular and cellular mechanisms. Chemotherapeutic agents and immunotherapy may
thus be synergistic and enhance the clinical response.
In this review, we show the rationale for combined chemo-immunotherapeutic strategies, and summarize recent data from clinical trials
performed in patients with different types of cancer. Challenges such as the selection of the optimal dose and treatment schedule, will be
discussed as well as the identification of immune-specific biomarkers. Furthermore, we evaluated the long-term clinical outcomes of
patients with advanced cervical cancer treated with HPV16 E6/E7 SLP vaccination with or without chemotherapy. Finally, the future of
vaccination therapy in combination with chemotherapy for the treatment of cervical cancer is discussed.
Keywords: Anti-cancer immunotherapy, cervical cancer, chemotherapy, combined chemo-immunotherapy, immune modulation.
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