Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

Abstract

Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis.

Exosomes from Macrophages Exposed to Apoptotic Breast Cancer Cells Promote Breast Cancer Proliferation and Metastasis

“…Additionally, nude mice treated with MCF-7 Co-exo cells had a lower body weight (Figure 7C) and had difficulty breathing, phenotypes that are similar to patients with clinically advanced tumors with metastasis. Clinically, breast cancer patients that relapse after chemotherapy often have a poor prognosis 65, which is consistent with our experimental results.…”

P-MAPA immunotherapy potentiates the effect of cisplatin on serous ovarian carcinoma through targeting TLR4 signaling

“…Cis-Diamminedichloroplatinum (cisplatin or “CIS”) is a potent antitumor agent, which is active against a variety of cancers, including OC [ 16 , 17 ]. Notably, the antineoplastic properties of CIS have been fully ascribed to its radiosensitizing effect and immunomodulatory ability [ 18 ].…”

A Phase I Trial of High-Dose Chemotherapy Combining Topotecan plus Cyclophosphamide with Hematopoietic Stem Cell Transplantation for Ovarian Cancer: The ITOV 01bis Study

“…Indeed, HDCT with hematopoietic stem cell support for solid tumors is currently used only in the setting of testicular germ cell tumors within structured trials conducted essentially in specialized referral centers [32]. However, even in this setting, the superiority of high doses over conventional chemotherapy as the first salvage treatment is still debated and a randomized phase III trial is in progress to address this issue [33].…”