Current strategies to minimize toxicity of oxaliplatin

Abstract

Oxaliplatin is an anticancer drug routinely used to treat colorectal, gastroesophageal, ovarian, breast, head/neck, and genitourinary cancers. Discontinuation of oxaliplatin treatment is mostly because of peripheral neuropathy, more often than for tumor progression, potentially compromising patient benefit. Several strategies to prevent neurotoxicity have so far been investigated. To overcome this life-threatening side effect, while taking advantage of the antineoplastic activities of oxaliplatin, we describe in detail recent findings on the underlying mechanisms of genetic variants associated with toxicity and resistance to oxaliplatin-based chemotherapy in colorectal cancer. A comprehensive panel of eight polymorphisms, previously validated as significant markers related to oxaliplatin toxicity, is proposed and discussed. In addition, the most common available strategies or methods to prevent/minimize the toxicity were described in detail. Moreover, an early outline evaluation of the genotyping costs and methods was taken in consideration. With the availability of individual pharmacogenomic profiles, the oncologists will have new means to make treatment decisions for their patients that maximize benefit and minimize toxicity. With this purpose in mind, the clinician and lab manager should cooperate to evaluate the advantages and limitations, in terms of costs and applicability, of the most appropriate pharmacogenomic tests for routine incorporation into clinical practice.

An albumin-based tumor-targeted oxaliplatin prodrug with distinctly improved anticancer activity in vivo

“…4 Nevertheless, the low selectivity of platinum( ii ) drugs towards cancer cells and cancerous tissue, together with severe adverse effects are still major disadvantages. 5,6 An approach to enhance the selectivity are platinum( iv ) prodrugs, which are chemically more inert and thus less cytotoxic. After entering the hypoxic, reductive conditions of the cancerous tissue, they are reduced and release their active, highly cytotoxic Pt( ii )-core (activation by reduction).…”

Chemotherapy Alone for Patients With Stage II/III Rectal Cancer Undergoing Radical Surgery

“…Our results compared favorably with pCR rates of 8%-15% among historical controls treated with fluoropyrimidine-based CRT in patients with locally advanced rectal cancer [6,[18][19][20][21][22][23][24][25][26][27][28]. Based on its role in resected stage III colon cancer and its radiosensitizing properties, the addition of oxaliplatin to the standard fluoropyrimidine-based CRT was tested in many studies [1].…”

“…The Food and Drug Administration reported that more than 70% of patients receiving oxaliplatin had some degree of peripheral neuropathy [20], which is often the cause for treatment discontinuation. Despite these adverse life-altering side effects, oxaliplatin therapy is a treatment choice in a large group of cancer patients, including those with colorectal cancer [21]. In this study, this approach (preoperative fluorouracil, leucovorin, and oxaliplatin withnoradiotherapy [RT])inpatients with locally advanced rectal cancer was tested in a prospective pilot study.…”

Targeting DNA Repair Pathways for Cancer Treatment: what’s new?

“…Modulation of DNA repair elements to treat CIPN is an emerging field. Ongoing studies are investigating diagnostic markers, molecular mechanisms, drug comparisons and potential treatments for CIPN [116–118]. Development of an effective small-molecule DNA repair inhibitor would be a first-in-class drug for neuropathic pain, which could change both survival and quality-of-life outcomes for many cancer patients.…”