Untitled

Abstract

The Mayo Clinic regimen of leucovorin 20 mg/m followed immediately by 5-fluorouracil 425 mg/m administered for 5 consecutive days every 4 weeks is commonly used in the treatment of colorectal cancer. This study was aimed at prospectively determining the incidence and pattern of severe toxicity associated with this regimen. We evaluated prospectively 243 patients with colorectal cancer treated in our department with the Mayo Clinic regimen for the incidence of severe toxicity (defined as toxicity requiring hospitalization). Of the 243 patients, 32 (13%) were hospitalized for chemotherapy-related toxicity. Major toxicities included neutropenic fever in 21 (9%), grade III/IV mucositis in 25 (10%) and grade III/IV diarrhea in 20 (8%). There were five (2%) treatment-related deaths. Female patients exhibited a higher incidence of severe toxicity (18%) and toxic death (4/105) than did male patients (9% and 1/138, respectively). Elderly patients (> or =70 years) had a higher incidence of severe toxicity than younger patients did (24% versus 7%, < 0.001). Toxic death occurred in 4 of 89 patients aged 70 years or more compared to 1 of 154 in younger patients. Most episodes of severe toxicity (56%) and toxic deaths (4/5) were observed after the first cycle. We conclude that the Mayo Clinic regimen can be associated with severe toxicity, usually occurring after the first cycle. Female gender and advanced age predict severe toxicity; therefore, dose reduction in high-risk patients should be considered, especially during the first cycle.

Predicting 5-fluorouracil toxicity in colorectal cancer patients from peripheral blood cell telomere length: a multivariate analysis

“…The observed clinical toxicity profiles were consistent with those reported in other patient cohorts with the Mayo schedule inducing significantly greater toxicity than the weekly schedule (Tsalic et al , 2003; Patel et al , 2004). The more aggressive Mayo therapy was characterised by a greater incidence of neutropenia, leukopenia and mucositis, whereas the principal toxicity in the less aggressive weekly schedule was diarrhoea.…”

“…The traditional practice of normalising dose to body surface area (BSA) takes into account only two variables (height and weight). Not surprisingly, patients experience a wide range of toxicities and severities, with the primary dose-limiting complications being neutropenia, leukopenia, mucositis and diarrhoea (Tsalic et al , 2003; Patel et al , 2004). There is clearly a need for better pretreatment markers that can predict for 5FU-induced toxicity in CRC patients well in advance of their chemotherapy.…”

A randomised controlled phase II trial of pre-operative celecoxib treatment reveals anti-tumour transcriptional response in primary breast cancer

“…Dvory-Sobol and colleagues demonstrated that celecoxib induces G2/M arrest associated with cyclin-B1 down-regulation in K-RAS -transformed enterocytes [38], and in the COX-2 expressing murine breast cancer cell line MCa-35, celecoxib induced a G2/M arrest followed by apoptosis [39]. Interestingly, equally treated lung cancer A549 cells lacking COX-2 expression showed increased DNA damage, but low levels of apoptosis in these cells suggested a selective effect of celecoxib on COX-2 expressing cells [39]. Celecoxib seems to increase DNA damage in irradiated cells, enhancing their radiosensitivity [40].…”

The impact of low-grade toxicity in older people with cancer undergoing chemotherapy

“…There are often concerns of increased risk of toxicity in older people ( Lichtman et al , 2007 ; Wedding et al , 2007 ). Some studies indicate increased toxicity with age ( Stein et al , 1995 ; Tsalic et al , 2003 ; Jantunen et al , 2006 ). However, these studies did not control for comorbidities that may equally affect tolerance to chemotherapy.…”