Platinum-Based Compounds for the Treatment of Metastatic Breast Cancer

Abstract

The role of platinum-based compounds (PBCs) in the treatment of metastatic breast cancer (MBC) has been extensively studied. As single agents, high response rates have been observed in first-line therapy, while results in pretreated patients were discouraging. Regimens containing cisplatin/carboplatin together with taxanes showed the highest efficacy and safety as both first-line and second-line therapy. When administered with vinorelbine, the combination was also active and well tolerated in anthracycline- and taxane-pretreated patients. Combining PBCs with etoposide or nucleoside analogues showed moderate activity, yet high toxicity in the case of etoposide. The overall results for the combination with anthracyclines were disappointing. Addition of trastuzumab to PBC combinations showed remarkable activity and good tolerability in patients with HER2/neu overexpression. The use of cisplatin or carboplatin alongside novel targeted therapeutics for patients with triple-negative MBC seems promising and is being further evaluated. The use of PBCs against MBC requires careful patient selection and combination with the right chemotherapeutic agent.

Cisplatin (CDDP) triggers cell death of MCF-7 cells following disruption of intracellular calcium ([Ca²⁺]_i) homeostasis

“…Recent efforts target new treatments to make BC sensitive to chemotherapy (Prabhakaran et al, 2013) while some platinum salts are promising drugs for future BC therapies (Biersack et al, 2012). Furthermore, using combinations of these compounds with docetaxel has been proven to be effective in advanced triple-negative BCs (Hurley et al, 2013;Shamseddine and Farhat, 2011;Eckstein and Haas, 2012) and the combinations of CDDP/carboplatin/taxanes showed the highest efficacy and safety in first-line and second-line therapy (Shamseddine and Farhat, 2011).…”

JNK implication in adipocyte-like cell death induced by chemotherapeutic drug cisplatin

“…Myo cell differentiation into adipocyte-like cells (ADC) was achieved by adding γ-linolenic acid to confluent cells in serum-containing medium. Our model involved the use of cis-diamminedichloroplatinum (II) (cisplatin) as an apoptosis inducer, cisplatin being one of the most commonly used anticancer drugs for treatment of a wide variety of tumors including metastatic breast cancer (Shamseddine and Farhat, 2011). Cisplatin forms intrastrand and interstrand crosslinks in DNA helix thus inhibiting DNA replication and transcription.…”

Methyl Sulfone Manifests Anticancer Activity in a Metastatic Murine Breast Cancer Cell Line and in Human Breast Cancer Tissue - Part 2: Human Breast Cancer Tissue

“…For example, treatment of breast cancer patients with capecitabine can cause cardiovascular toxicity [1], and treatment with platinum-based compounds can cause nephrotoxicity [for a review, see [2]].…”