Reintroduction of Oxaliplatin: A Viable Approach to the Long-Term Management of Metastatic Colorectal Cancer

Abstract

Oxaliplatin-based chemotherapy is an effective first-line treatment option for patients with metastatic colorectal cancer (mCRC), which, in combination with targeted therapies and a sequential treatment approach using all active agents, has extended median overall survival to 2 years and beyond. Prolonged survival brings into focus the burden of treatment, in terms of associated toxicities and quality of life, and attention is now being paid to lowering the toxicity burden for patients receiving chemotherapy for mCRC without compromising efficacy. The use of oxaliplatin can lead to the development of sensory neuropathy, which commonly limits the dose and/or duration of treatment that can be administered. Temporary withdrawal of oxaliplatin (treatment holidays) has been shown to be an effective strategy for the management of this adverse effect. Data from randomized controlled trials indicate that a formalized stop-and-go approach to the delivery of oxaliplatin does not compromise efficacy, and indeed for some patients may prove beneficial by allowing them to continue treatment for longer periods. This paper presents a critical review of the evidence to support the utility of treatment interruption and reintroduction of oxaliplatin for the long-term management of mCRC.

Drug rechallenge and treatment beyond progression—implications for drug resistance

“…17,18 Consequently, incorporating chemotherapy-free intervals into treatment algorithms has become important for the management of patient quality of life, particularly with regard to oxaliplatin treatment, which can cause an accumulation of neurological toxic effects. 19 Retrospective data indicate a benefit of interrupting FOLFOX therapy and reintroducing it at relapse, typically with a different regimen, with a high rate of response or disease stabilization at reintroduction. 19,20 Compared to other follow-up therapies, rechallenge with FOLFOXIRI (FOLFOX plus irinotecan) was shown to yield a significantly longer progression-free survival (PFS; 8.2 months rechallenge versus 6.3 months for other therapies, P = 0.003) and overall survival (19.3 versus 14.0 months, respectively, P = 0.02).…”

“…19 Retrospective data indicate a benefit of interrupting FOLFOX therapy and reintroducing it at relapse, typically with a different regimen, with a high rate of response or disease stabilization at reintroduction. 19,20 Compared to other follow-up therapies, rechallenge with FOLFOXIRI (FOLFOX plus irinotecan) was shown to yield a significantly longer progression-free survival (PFS; 8.2 months rechallenge versus 6.3 months for other therapies, P = 0.003) and overall survival (19.3 versus 14.0 months, respectively, P = 0.02). 21 …”

“…27 Overall, oxaliplatin rechallenge demonstrates similar efficacy to continuous regimens, but rechallenge might be preferred for the long-term management of CRC given its improved tolerability. 19 …”

Prechemotherapy Touch Sensation Deficits Predict Oxaliplatin-Induced Neuropathy in Patients with Colorectal Cancer

“…Oxaliplatin, in combination with 5-fluorouracil, leucovorin, capecitabine, and/or irinotecan, is a common chemotherapy regimen for CRC that confers significant clinical benefit in terms of progression-free survival and response rates [2–4]; however, oxaliplatin is also neurotoxic [5]. …”

HOCl Oxidation-modified CT26 Cell Vaccine Inhibits Colon Tumor Growth in a Mouse Model

“…For patients with metastatic colorectal cancer (mCRC), oxaliplatin-based first line chemotherapy has been demonstrated to extend median overall survival to 2 years and beyond. However, adverse effects such as neurotoxicity brings the poor quality of life for patients receiving chemotherapy (Grothey, 2010).…”