Platinum drugs in the treatment of non-small-cell lung cancer

Abstract

The use of chemotherapy is considered standard therapy in patients with locally advanced non-small-cell lung cancer that cannot be treated with radiotherapy and in those with metastatic non-small-cell lung cancer and good performance status. This approach is also accepted in patients with earlier stage disease, when combined with radiotherapy in those with nonresectable locally advanced disease, or in the preoperative setting. Randomised clinical studies and meta-analyses of the literature have confirmed the beneficial survival effect of platinum-based chemotherapy. Cisplatin and carboplatin have been successfully used with other drugs in a wide variety of well-established two-drug combinations while three-drug combinations are still under investigation. Cisplatin and carboplatin use is limited by toxicity and inherent resistance. These considerations have prompted research into new platinum agents, such as the trinuclear platinum agent BBR3464, the platinum complex ZD0473 and oxaliplatin. These compounds could be developed in combination with agents such as paclitaxel, gemcitabine or vinorelbine in patients with advanced and/or refractory solid tumours.

Hierarchical involvement of Bak, VDAC1 and Bax in cisplatin-induced cell death

“…After an initial, pyrrhic success leading to partial therapeutic responses or stabilization of the disease, chemotherapy-resistant tumor cells are selected, imposing successive changes in the chemotherapeutic regimen. Almost invariably, chemotherapy becomes ineffective and the patient eventually succumbs to the disease (Cosaert and Quoix, 2002;Seve and Dumontet, 2005). Thus, the comprehension of CDDP-induced cell death mechanisms may have direct clinical implications for the design of therapeutic regimens that overcome CDDP resistance.…”

Ex Vivo Explant Cultures of Non–Small Cell Lung Carcinoma Enable Evaluation of Primary Tumor Responses to Anticancer Therapy

“…A number of mechanisms have been reported to render cells resistant to cisplatin including reduced drug uptake, enhanced export, drug deactivation, increased repair of DNA damage, or alterations in apoptosis (33,34). To examine drug uptake/export, we investigated Pt ion distribution across explant tissue using LA-ICP-MS (see Supplementary Fig.…”

An ERK-dependent pathway to Noxa expression regulates apoptosis by platinum-based chemotherapeutic drugs

“…Cisplatin therapy is effective for the treatment of many cancer types including testicular cancer, non-small-cell lung cancer, head and neck cancers, advanced cervical carcinomas and ovarian cancers (Cosaert and Quoix, 2002;Hao et al, 2006;Pectasides et al, 2008;Muggia, 2009). In particular, testicular cancers are highly responsive to cisplatin treatment and this chemotherapeutic agent efficiently eradicates early stage testicular tumors (Kollmannsberger et al, 2006).…”