Abstract
BackgroundNew chemotherapy regimens for patients with colorectal cancer have improved survival, but at the cost of clinical toxicity. Oxaliplatin, an agent used in first-line therapy for metastatic colorectal cancer, causes acute and chronic neurotoxicity. This study was performed to carefully assess the incidence, type and duration of oxaliplatin neurotoxicity.MethodsA detailed questionnaire was completed after each chemotherapy cycle for patients with metastatic colorectal cancer enrolled in a phase I trial of oxaliplatin and capecitabine. An oxaliplatin specific neurotoxicity scale was used to grade toxicity.ResultsEighty-six adult patients with colorectal cancer were evaluated. Acute neuropathy symptoms included voice changes, visual alterations, pharyngo-laryngeal dysesthesia (lack of awareness of breathing); peri-oral or oral numbness, pain and symptoms due to muscle contraction (spasm, cramps, tremors). When the worst neurotoxicity per patient was considered, grade 1/2/3/4 dysesthesias and paresthesias were seen in 71/12/5/0 and 66/20/7/1 percent of patients. By cycles 3, 6, 9, and 12, oxaliplatin dose reduction or discontinuation was needed in 2.7%, 20%, 37.5% and 62.5% of patients.ConclusionOxaliplatin-associated acute neuropathy causes a variety of distressing, but transient, symptoms due to peripheral sensory and motor nerve hyperexcitability. Chronic neuropathy may be debilitating and often necessitates dose reductions or discontinuation of oxaliplatin. Patients should be warned of the possible spectrum of symptoms and re-assured about the transient nature of acute neurotoxicity. Ongoing studies are addressing the treatment and prophylaxis of oxaliplatin neurotoxicity.
Highlights
New chemotherapy regimens for patients with colorectal cancer have improved survival, but at the cost of clinical toxicity
The standard chemotherapy regimen used as first-line treatment of colorectal cancer for many years was bolus 5FU modulated by (LV), but this has recently been superseded by newer combination regimens involving LV-modulated 5-FU given as a mixed bolus and continuous infusion with the addition of either oxaliplatin or irinotecan
A randomized trial comparing sequential administration of biweekly LV-modulated mixed bolus and infusional 5-FU combined with either oxaliplatin (FOLFOX 4) or irinotecan (FOLFIRI) followed by the other regimen at the time of disease progression showed equivalent survival of about 21 months for both sequences [5]
Summary
New chemotherapy regimens for patients with colorectal cancer have improved survival, but at the cost of clinical toxicity. A Phase III trial in patients with metastatic colorectal cancer comparing oxaliplatin and biweekly LV-modulated mixed bolus and infusional 5-FU (FOLFOX 4) to bolus 5-FU/LV given daily for five days every month demonstrated superiority in both response rate and progression-free survival [3]. Another Phase III trial demonstrated a significant survival advantage with FOLFOX-4 compared to irinotecan and bolus 5-FU/LV (median survival 19.5 vs months, p = 0.0001) [4]. A randomized trial comparing sequential administration of biweekly LV-modulated mixed bolus and infusional 5-FU combined with either oxaliplatin (FOLFOX 4) or irinotecan (FOLFIRI) followed by the other regimen at the time of disease progression showed equivalent survival of about 21 months for both sequences [5]. Oxaliplatin has shown activity in other platinum-sensitive tumors, including in some cancer patients with documented cisplatin-refractory disease [6,7,8]
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