Adjuvant Treatment Of Colorectal Cancer Research Articles

Do nutraceutics play a role in the prevention and treatment of colorectal cancer?

Colorectal cancer is the third most common cancer worldwide with a 5-year survival of 50%. Current chemotherapeutic regimens used for advanced colorectal cancer provide an average survival of approximately 20 months. Non-toxic agents such as nutraceutics and supplements have been shown to aid in the prevention and adjuvant treatment of colorectal cancer. This article will discuss the epidemiology, progression, prevention, treatment, and recurrence of colorectal cancer and the role of nutraceutics and supplements in the treatment process.

Acute Immune-Mediated Thrombocytopenia Due to Oxaliplatin Administration: A Case Report

Drug-induced acute thrombocytopenia is an extremely rare side effect that may occur immediately after oxaliplatin infusion. This potentially fatal reaction is immune mediated and can be anticipated by mild hemorrhagic signs during previous administrations. This is the first report of acute thrombocytopenia occurring during adjuvant treatment of colorectal cancer with oxaliplatin. Clinicians should be aware of this adverse event in order to prevent possible serious consequences and stop further oxaliplatin administration.

Is laparoscopic colorectal cancer surgery equal to open surgery? An evidence based perspective

Laparoscopic colorectal surgery (LCS) is an evolving subject. Recent studies show that LCS can not only offer safe surgery but evidence is growing that this new technique can be superior to classical open procedures. Fewer perioperative complications and faster postoperative recovery are regularly mentioned when studies of LCS are presented. Even though the learning curve of LCS is frequently debated when limitations of laparoscopic surgeries are reviewed, studies show that in experienced hands LCS can be a safe procedure for colorectal cancer treatment. The learning curve however, is associated with high conversion rates and economical aspects such as higher costs and prolonged hospital stay. Nevertheless, laparoscopic colorectal cancer surgery (LCCR) offers several advantages such as less co-morbidity and less postoperative pain in comparison with open procedures. Furthermore, the good exposure of the pelvic cavity by laparoscopy and the magnification of anatomical structures seem to facilitate pelvic dissection laparoscopically. Moreover, recent studies describe no difference in safety and oncological radicalness in LCCR compared to the open total mesorectal excision (TME). The oncological adequacy of LCCR still remains unproven today, because long-term results do not yet exist. To date, only a few studies have described the results of laparoscopic TME combined with preoperative adjuvant treatment for colorectal cancer. The aim of this review is to examine the various areas of development andcontroversy of LCCR in comparison to the conventional open approach.

Abstract B190: Efficacy of the specific ETA receptor antagonist zibotentan (ZD4054) in cancer cells and fibroblasts from colorectal cancer

Abstract Endothelin-1 (ET-1) contributes to growth and progression of solid cancers, mainly through endothelin receptor A (ETAR). Therefore endothelin receptor antagonism is emerging as a potential treatment for neoplasms. We evaluated the efficacy of the specific ETAR antagonist zibotentan (ZD4054) in blocking ET-driven cellular effects in colorectal cancer (CRC). CRC cell lines (HT29, SW620) and primary normal fibroblast strains isolated from human colorectal tissues (CF36, CF56, CF65, CF75) were incubated in ET-1 with/without BQ123, zibotentan (ETAR antagonists), BQ788 (ETBR antagonist). Resultant cell growth was measured by the colourimetric methylene blue assay; migration by a modified monolayer scratch assay; contraction in collagen gels; downstream effectors by western blotting. ET-1 driven growth (18%–45% above control) was significantly inhibited (p<0.01) by ETAR (not ETBR) antagonism (BQ123=zibotentan CRC; fibroblasts). ET-1 driven fibroblast migration and contraction were blocked by ETAR and ETBR antagonism (zibotentan=BQ123). CRC cells did not migrate or contract. ET-1-stimulated expression of downstream effectors was driven by ETAR or ETBR, eg: (1) connective tissue growth factor (CTGF) was blocked by ETAR antagonism (zibotentan>BQ123; CRC and fibroblasts); (2) collagen XI was blocked by ETAR>ETBR antagonism (zibotentan>BQ123; fibroblasts). The specific ETAR antagonist zibotentan is at least as efficacious as BQ123 in blocking ET-1 driven growth, migration and contraction both in CRC cells and colorectal fibroblasts, which form the supporting tumor stroma. Zibotentan is a strong candidate for adjuvant treatment in CRC. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B190.

Involvement of drug transporters in the synergistic action of FOLFOX combination chemotherapy

FOLFOX is a cytostatic drug combination for adjuvant treatment of colorectal cancer (CRC) consisting of 5-fluorouracil (5-FU), leucovorin, and oxaliplatin. The mechanism of synergistic interaction of these drugs is poorly understood and little is known concerning the role of drug transporters and the impact of oxaliplatin metabolites oxalate and dichloro-diaminocyclohexane platinum. We therefore investigated the influence of FOLFOX components on drug transporter expression by quantitative real-time polymerase chain reaction and on the efficacy of each FOLFOX component by proliferation assay in the CRC model cell line LS180. Control experiments with transporter over-expressing cell lines were used to assess the significance of important transporters for the cytostatic activity of FOLFOX components. Moreover, we assessed the pharmacological contribution of the oxalato-ligand to the effect of oxaliplatin. FOLFOX components led to several alterations in expression of drug transporters. For instance, 5-FU significantly suppressed ATP7B and human organic cation transporter 2 and increased multidrug resistance-associated protein (MRP) 2 mRNA expression (5.8-fold). This was accompanied by a significant sensitisation to oxaliplatin. Over-expression of certain ABC-transporters (BCRP/ABCG2, MRP2/ABCC2 or MRP3/ABCC3) was demonstrated to be beneficial for the efficacy of oxaliplatin. The results obtained indicate that both down- and up-regulations of drug transporters could favour synergistic action of this drug combination. Moreover, oxaliplatin metabolite oxalate seems to positively modulate oxaliplatin's action as elucidated by median effect analysis. In conclusion, we propose as one mechanism for FOLFOX synergism the 5-FU mediated suppression of ATP7B, the over-expression of glutathione exporters such as MRP2/ABCC2 and the decrease of glutathione levels by oxalate.

Administration of reduced glutathione in FOLFOX4 adjuvant treatment for colorectal cancer: effect on oxaliplatin pharmacokinetics, Pt-DNA adduct formation, and neurotoxicity

Oxaliplatin is a promising drug for cancer therapy and the oxaliplatin/5-fluorouracil/leucovorin (FOLFOX) regimen has become the standard adjuvant treatment for colorectal cancer. However, the oxaliplatin-induced neurotoxicity still represents a clinical problem leading to a discontinuation of the therapy. Many strategies have been proposed in order to manage the neurotoxicity, but their effect on antitumoral efficacy is still unclear. In this study, we investigated the effect of reduced glutathione administration on neurotoxicity, oxaliplatin pharmacokinetics, and platinum-DNA (Pt-DNA) adduct formation in patients affected by colorectal cancer treated with FOLFOX4 adjuvant regimen. Twenty-seven patients were randomized to receive GSH 1500 mg/m or saline solution before oxaliplatin infusion. Evaluation of neurotoxicity, pharmacokinetics of plasmatic total and ultrafiltered Pt, and determination of Pt-DNA adduct formation on white blood cells was performed during the 5th, 9th, and 12th cycles. At the end of all cycles of therapy, the patients in the GSH arm showed a statistically significant reduction of neurotoxicity (P=0.0037) compared with the placebo arm. There were no significant differences in the main pharmacokinetic parameters between the two arms except a lower area under the plasma concentration-time curve and a smaller apparent steady-state volume of distribution (Vss) when GSH was coadministered. This difference can be explained by the natural function of GSH in the detoxification of oxaliplatin and by its ability to remove the Pt bound to plasma proteins. The determination of Pt-DNA adduct formation shows no statistically significant differences between the two arms. In conclusion, this study indicates that coadministration of GSH is an effective strategy to reduce the oxaliplatin-induced neurotoxicity without impairing neither the pharmacokinetics of oxaliplatin, nor the Pt-DNA adduct formation.

XELOX versus FOLFOX6 as an adjuvant treatment in colorectal cancer: an economic analysis

ABSTRACTObjectives: An economic analysis (based on interim data from a long-term, randomised, multi-centre, controlled, clinical trial) to evaluate chemotherapy with XELOX (capecitabine/oxaliplatin) versus FOLFOX6 (5Fluorouracil/leucovorin/oxaliplatin) as an adjuvant treatment for high risk colorectal cancer patients in Greece.Methods: As survival rate was the same in the two arms, a cost-minimisation analysis was carried out, from the perspectives of the National Health Service (NHS), Social Insurance Funds (SIF) and patients in Greece. Patient data were combined with 2008 unit prices to estimate the total cost of patient care, the patients’ travelling expenditure and their productivity losses. Raw data were bootstrapped 5000 times in order to allow statistical testing.Results: From an NHS perspective, the mean chemotherapy cost was €8762 with FOLFOX6 and €9713 with XELOX; costs of administration and hospitalisations were €5154 and €1050, respectively. Total treatment cost with FOLFOX6 reached €17 480 and with XELOX €12 525, a difference of €4955 (p < 0.001) in favour of the latter therapy. From an SIF perspective, the total cost of treatment was €16 240 with FOLFOX6 and €12 617 with XELOX, a reduction of €3623 (p < 0.001) with the latter therapy. Mean patient travelling cost was €184 with FOLFOX6 and €80 with XELOX, a difference of €104 (p < 0.001). Mean productivity loss was €100 with FOLFOX6 and €31 with XELOX, a difference of €69 (p < 0.001).Conclusions: Chemotherapy combining oral capecitabine and oxaliplatin reduces total treatment cost for the Greek National Health Service and Social Insurance Funds, mainly through a reduction in the cost of administration. From patients’ perspective, it reduces travelling expenditure and productivity losses. Therefore, this combination may be a cost-effective approach for the management of colorectal cancer patients who have had surgery in Greece. This is an analysis alongside a clinical trial, and should be interpreted in this specific context in which it was undertaken.

Hand-foot Syndrome Following Capecitabine (Xeloda®) Monotherapy for Colorectal Cancer

Purpose: Capecitabine (Xeloda), which is a systemic prodrug of 5-fluorouracil, can be used in oral formulation for treatment of advanced colorectal cancer as a 1st line or an alternative modality to I.V. 5-fluorouracil-based chemotherapy. One of the most common side effects of this drug is hand-foot syndrome (HFS), palmar-plantar erythrodysesthesia syndrome. We planned this study to clarify the incidence and the clinical course of severe hand-foot syndrome (WHO classification, grade 3 or 4) following capecitabine monotherapy for adjuvant treatment of colorectal cancer. Methods: From August 2006 to August 2008, 45 colorectal cancer patients were treated with capecitabine, 1,250 mg/m2, orally administered twice daily for 2 wk, followed by 1 wk of rest, given as 3-wk cycles. Seven of them discontinued the drug within 3rd cycle due to poor performance status, gastrointestinal troubles, or other causes. We retrospectively analyzed the remaining 38 patients' medical records and defined the incidence and the clinical course of HFS. Results: Of the 38 patients, 17 (44.7%) suffered severe HFS after capecitabine monotherapy. Of those 17, 5 (29.4%) had severe symptoms after the 1st chemotherapy cycle, and 14 patients (82.4%) had severe symptoms within the 4th cycle. Three of the 14 female and 14 of the 24 male patients complained of severe HFS, showing a statistical male predominance (P= 0.043). Eventually, we had to decrease capecitabine to 75% of the daily dose in 12 patients and to 50% in one patient, and to discontinue its use in 4 patients. Conclusion: Capecitabine monotherapy very frequently provokes severe HFS, especially in the early cycles of chemotherapy and in males.

Adjuvant treatment in colorectal cancer

Adjuvant treatment in colorectal cancer

Fatal pneumonitis induced by oxaliplatin

Oxaliplatin has been approved for adjuvant treatment of colorectal cancer. Toxicity induced by oxaliplatin is moderate and manageable, but some isolated cases of severe pulmonary toxicity associated to oxaliplatin have been reported. Two fatal cases of interstitial pneumonitis rapidly evolving to pulmonary fibrosis are reported here.

Combined Chemotherapy of Hydroxycampothecin with Oxaliplatin as an Adjuvant Treatment for Human Colorectal Cancer

Colorectal cancer (CRC) is a major cause of morbidity and mortality for cancer worldwide, but many patients with CRC are resistant to chemotherapy. We therefore investigated the therapeutic mechanism and clinical effect of combined chemotherapy of hydroxycampothecin (HCPT) with oxaliplatin (L-OHP) on CRC. HCPT represents a potential antitumor agent of Chinese herb. Mice carrying the xenografted human LS174T CRC cells were injected into peritoneal cavities with different drugs: HCPT + L-OHP (OH), HCPT, L-OHP, or saline. Treatment of mice with OH caused the decrease in the volume of tumor and the expression of p53, but increased the apoptotic rate and Fas-L expression, compared to those of animals treated with HCPT or L-OHP, or control animals. Thus, the combination of HCPT with L-OHP could more effectively induce the apoptosis of CRC cells. Furthermore, 56 patients with CRC were treated with HCPT and L-OHP (28 cases, OH group) or L-OHP plus leucovorin plus 5-fluorouracil (28 cases, OFL group), then reviewed the response rate, survival rate and toxicity. The one-year survival rate was 35.07% in OH group and 24.21% in OFL group. However, the occurrence of anemia (51.8%) or diarrhea (60.7%) was higher in OH group than that of 19.6% or 46.4% in OFL group. The clinical results suggest that HCPT plus L-OHP combined chemotherapy could increase the survival time of patients. Taken together, the present study indicates that the combined chemotherapy of HCPT with L-OHP could become a new adjuvant treatment for CRC.

Altered endothelin receptor subtypes in colorectal cancer

The vasoactive peptide endothelin-1 (ET-1) acts via two endothelin receptor subtypes, ETA (ETAR) and ETB (ETBR). ET-1 and ETAR are overexpressed in colorectal cancer tissues. In vitro, ET-1 acting via ETAR, is a mitogen for colorectal cancer cells. To identify other potential stimulatory loops, we investigated the distribution and cell-specific localization of both ETAR and ETBR in tissue sections from patients with colorectal cancer. Frozen sections from specimens of colorectal cancer (n=9) and normal colon (n=9) were cut and subjected to either (i) autoradiography or (ii) a combination of cell type-specific immunohistochemistry, using antibodies against fibroblasts (AS02), endothelial cells (CD31) or nerve fibres (NF200) and in-vitro receptor microautoradiography, using ETAR-specific and ETBR-specific radioligands. ETARs were upregulated in all cell types, apart from nerve, in cancer compared with normal colon (1:1.59 normal to cancer). Specifically, ETAR binding was highest in cancer-associated blood vessels and fibroblasts and to a lesser extent in epithelial cancer cells. In contrast, ETBRs were the predominant receptors in normal colon (1:0.59 normal to cancer) and were markedly down-regulated in cancer-associated blood vessels, fibroblasts and to a lesser extent in epithelial cells. Nerve colocalization was demonstrated, but remained unchanged for all tissues. The shift in ET receptor binding observed in epithelial cancer cells and cancer-associated fibroblasts and endothelial cells may favour ET-1 signals contributing to colorectal cancer growth and neovascularization via ETAR. This may provide the basis for therapeutic use of specific ETAR antagonists as adjuvant treatment of colorectal cancer.

The Effect of Statins in Colorectal Cancer Is Mediated Through the Bone Morphogenetic Protein Pathway

Epidemiological evidence suggests that statins prevent colorectal cancer (CRC), but the biological mechanism remains obscure. Statins induce bone morphogenetic protein (BMP) expression in bone cells. We have previously shown that BMPs act as tumor suppressors in CRC. We hypothesized that the action of statins in CRC involves the induction of BMPs. We investigated the effects of statins on CRC cell lines using immunoblotting, measurements of apoptosis and cell proliferation, and luciferase reporter assays. The effect of statins was confirmed in a xenograft mouse model. CRC cell lines show widely differing sensitivities to statin treatment. Sensitive cell lines show induction of BMP2 protein levels and a BMP2 reporter construct, activation of the BMP pathway, and induction of the BMP target gene ID-2, whereas resistant cell lines do not. The addition of the specific inhibitor of BMPs, noggin, completely prevents lovastatin-induced apoptosis in sensitive cells. Sensitive cell lines express the central BMP pathway element SMAD4, whereas the resistant cell lines do not. Targeted knockout of SMAD4 leads to the loss of statin sensitivity and reconstitution with SMAD4, to the restoration of statin sensitivity. In a xenograft mouse model, tumors from sensitive and insensitive cell lines were treated with oral simvastatin. Significant inhibition of tumor growth using sensitive cells but increased tumor growth when using insensitive cells was observed. Statins induce apoptosis in CRC cells through induction of BMP2. Statin therapy may only be effective in SMAD4-expressing CRCs and may have adverse effects in SMAD4-negative tumors.

Rofecoxib and Cardiovascular Adverse Events in Adjuvant Treatment of Colorectal Cancer

Selective cyclooxygenase inhibitors may retard the progression of cancer, but they have enhanced thrombotic potential. We report on cardiovascular adverse events in patients receiving rofecoxib to reduce rates of recurrence of colorectal cancer. All serious adverse events that were cardiovascular thrombotic events were reviewed in 2434 patients with stage II or III colorectal cancer participating in a randomized, placebo-controlled trial of rofecoxib, 25 mg daily, started after potentially curative tumor resection and chemotherapy or radiotherapy as indicated. The trial was terminated prematurely owing to worldwide withdrawal of rofecoxib. To examine possible persistent risks, we examined cardiovascular thrombotic events reported up to 24 months after the trial was closed. The median duration of active treatment was 7.4 months. The 1167 patients receiving rofecoxib and the 1160 patients receiving placebo were well matched, with a median follow-up period of 33.0 months (interquartile range, 27.6 to 40.1) and 33.4 months (27.7 to 40.4), respectively. Of the 23 confirmed cardiovascular thrombotic events, 16 occurred in the rofecoxib group during or within 14 days after the treatment period, with an estimated relative risk of 2.66 (from the Cox proportional-hazards model; 95% confidence interval [CI], 1.03 to 6.86; P=0.04). Analysis of the Antiplatelet Trialists' Collaboration end point (the combined incidence of death from cardiovascular, hemorrhagic, and unknown causes; of nonfatal myocardial infarction; and of nonfatal ischemic and hemorrhagic stroke) gave an unadjusted relative risk of 1.60 (95% CI, 0.57 to 4.51; P=0.37). Fourteen more cardiovascular thrombotic events, six in the rofecoxib group, were reported within the 2 years after trial closure, with an overall unadjusted relative risk of 1.50 (95% CI, 0.76 to 2.94; P=0.24). Four patients in the rofecoxib group and two in the placebo group died from thrombotic causes during or within 14 days after the treatment period, and during the follow-up period, one patient in the rofecoxib group and five patients in the placebo group died from cardiovascular causes. Rofecoxib therapy was associated with an increased frequency of adverse cardiovascular events among patients with a median study treatment of 7.4 months' duration. (Current Controlled Trials number, ISRCTN98278138 [controlled-trials.com].).

Chronopharmacokinetics of Oral Tegafur and Uracil in Colorectal Cancer Patients

Uracil-Ftorafur (UFT) combines the 5-fluorouracil (FU) prodrug tegafur with uracil (at a 1:4 molar ratio), which is a competitive inhibitor of dihydropyrimidine dehydrogenase (DPD), the limiting enzyme of FU catabolism. As a result, sustained FU concentrations are obtained in both plasma and tumor. UFT is an effective alternative to intravenous FU-Leucovorin (LV) in metastatic and adjuvant colorectal cancer treatment. A circadian rhythm for DPD activity has been shown in both human and animal studies, with consequences on FU plasma concentrations in patients receiving FU as a continuous infusion. The chronopharmacokinetics of FU has stimulated clinical trials of chronomodulated delivery schedules for floxuridine and FU infusions, suggesting that such schedules may improve the fluoropyrimidine therapeutic index. Molecular mechanisms responsible for the circadian dependence of FU pharmacodynamics include circadian rhythms in thymidylate synthase activity and DNA synthesis, as recently reported. Chronopharmacology of FU prodrugs is poorly documented. Recently, a feasibility study of chronomodulated administration of the FU oral prodrug capecitabine was reported. To our knowledge, the only study reporting on the time dependency of UFT pharmacokinetics is a phase I study by Muggia et al.

Choice of adjuvant and first-line metastatic chemotherapy (CT) for colorectal cancer (CRC) treated in the Carolinas

17039 Background: CT choice is influenced by many factors including published evidence, guidelines, cost, reimbursement, patient considerations, key opinion leaders, and anecdote. Substantial locoregional variation in practice patterns can exist, and therefore studies of locoregional practice provide important information on local drivers of care. Methods: Using a population-based strategy, we identified CRC patients who developed metastatic disease since 6/1/03 from 9 Duke Oncology Network community practices and 1 academic practice in North and South Carolina. Demographic, comorbidity, diagnostic, stage, initial treatment, and metastatic treatment data were abstracted by retrospective chart review, double-entered and verified for accuracy. Results: Of the first 743 charts screened, 306 were eligible (mean age 61 (SD 13), 49% male; 65% white; 22% black; 77% colon cancer and 19% rectal; stages II 8%, III 16%, IV 64%). 26 earlier stage rectal cancer patients received neoadjuvant treatment, 50% infusional fluorouracil (5FU) and 42% capecitabine (Cap). 46 colon cancer patients received adjuvant CT, including 5FU/leucovorin (LVN; 54%), 5FU/LVN/oxaliplatin (21%), Cap (9%), and 5FU/LVN/irinotecan (7%). First-line CT for metastatic colon cancer (n=149) included FOLFOX+-bevacizumab (Bev; 42%), Cap/oxaliplatin +- Bev (23%), 5FU/LVN + Bev (9%), FOLFIRI +- Bev (7%), IFL +- Bev (7%), clinical trial (7%), Cap (3%), and unknown (1%). 54% of patients received Bev overall, reflecting 49% usage before 6/05 and 69% after 6/05. CT was not offered for 25 (8%) at initial diagnosis. Conclusion: Locoregional practice patterns in the Carolinas suggest that for adjuvant treatment of CRC, oxaliplatin has been used in 21% of adjuvant and 75% of first-line metastatic colon CT regimens, and that bevacizumab use has increased to 69% of first-line metastatic CRC patients. No significant financial relationships to disclose.

Adjuvant Treatment of Colorectal Cancer

Colorectal cancer is the fourth most common noncutaneous malignancy in the United States and the second most frequent cause of cancer-related death. Approximately three quarters of patients are diagnosed with disease limited to the bowel wall or surrounding lymph nodes. Over the past decade, significant progress has been made in the treatment of localized colorectal cancer due to advances in surgery, radiotherapy, and chemotherapy. For patients with Stage III colon cancer, an overall survival benefit for fluorouracil-based chemotherapy has been firmly established, and recent data have shown further efficacy through the inclusion of oxaliplatin into adjuvant treatment programs. For patients with Stage II colon cancer, the use of adjuvant chemotherapy remains controversial, but may be appropriate in a subset of individuals at high risk for disease recurrence. In the treatment of patients with rectal cancer, improved outcomes have been noted with the use of total mesorectal excision and preoperative concurrent chemoradiotherapy. Current randomized clinical trials in the adjuvant therapy of colorectal cancer are examining the value of adding agents known to be active in metastatic disease, including those that modify specific molecular targets.

A prospective, blinded analysis of thymidylate synthase and p53 expression as prognostic markers in the adjuvant treatment of colorectal cancer

BackgroundDespite previous studies, uncertainty has persisted about the role of thymidylate synthase (TS) and p53 status as markers of prognosis in colorectal cancer (CRC). Patients and methodsA total of 967 patients accrued to a large adjuvant trial in CRC were included in a prospectively planned molecular substudy, and of them, 59% had rectal cancer and about 90% received adjuvant chemotherapy (either systemically or randomly allocated to intraportal 5-fluorouracil infusion or both). TS and p53 status were determined, blinded to any clinical data, by immunohistochemistry using a validated polyclonal antibody or the DO-7 clone, respectively, and their relationships with overall survival were examined. ResultsHigh TS expression was observed in 58% and overexpression of p53 in 60% of tumours. TS expression correlated with tumour stage, and p53 overexpression, with rectal cancers. There was no evidence that either marker was significantly associated with survival by either univariate (TS hazard ratio (HR) = 0.94, 95% CI 0.76–1.18 and P = 0.6 and p53 HR = 0.98, 95% CI 0.78–1.23 and P = 0.9) or multivariate analyses (TS HR = 0.99, 95% CI 0.79–1.25 and P = 0.9 and p53 HR = 0.98, 95% CI 0.78–1.23 and P = 0.8). ConclusionsNeither TS nor p53 expression has significant prognostic value in the adjuvant setting of CRC.

Weekly Fluorouracil at 425 mg/m 2 plus Low-dose Folinic Acid for 24 Weeks as Adjuvant Treatment for Colorectal Cancer: Assessment of Toxicity and Delivery

Aims To assess the toxicity and dose delivery of weekly bolus 5-fluorouracil (5-FU) at 425 mg/m 2 plus low-dose folinic acid (FA) for 24 weeks as adjuvant treatment for colorectal cancer. Materials and methods Data were collected on toxicity and dose reductions, stoppages, delays and intensity from 100 consecutive patients receiving this adjuvant regimen after curative surgery. Results There were 53 men and 47 women (median age: 64 and 65 years, respectively); 77 patients with colon cancer and 23 with cancer of the rectum; 34 patients with Dukes' stage B and 66 with Dukes' stage C. Thirty-seven patients experienced at least one grade 3 or 4 toxicity, mainly diarrhoea (20 patients) or fatigue (14 patients). Only one grade 4 toxicity was noted (diarrhoea). In multivariate analysis, increased grade 3 and 4 toxicity was significantly associated with female gender ( P = 0.001) and age >65 years ( P = 0.046). Forty patients completed the 24 cycles without dose reduction or delay. Forty-one patients required at least one dose reduction. The median ‘conventional’ dose intensity (DI), calculated from the first cycle to the last, was 408 mg/m 2/week (96%). The median DI over 24 weeks was 387 mg/m 2/week (91%). A higher median 24-week DI was delivered to men (407 mg/m 2/week, 96%) than women (361 mg/m 2/week, 85%; P = 0.009). Women older than 65 years showed a significantly reduced median DI over 24 weeks (347 mg/m 2/week, 82%) compared with men aged 65 years or younger (407 mg/m 2/week, 96%; P = 0.049) and men older than 65 years (425 mg/m 2/week, 100%; P = 0.001), although the difference against women aged 65 years or younger (377 mg/m 2/week, 89%) was not statistically significant ( P = 0.09). Conclusion This regimen has shown what might be considered high rates of grade 3 and 4 toxicity for an adjuvant treatment, although the delivered DI was acceptable. Caution is urged in the treatment of elderly female patients who have statistically higher rates of grade 3 and 4 toxicity and lower DI.

Capecitabine: A New Adjuvant Option for Colorectal Cancer

Colorectal cancer continues to pose a major public health threat in the United States. Without postsurgical adjuvant therapy, approximately 50% of patients will have recurrent disease and die within five years. Since 1990, five new chemotherapy agents have been added to the therapeutic armamentarium for management of colorectal cancer, and agents traditionally used to treat metastatic and advanced disease increasingly are being applied in the adjuvant setting. One such treatment, capecitabine, offers patients the benefit of oral dosing and permits at-home self-management. A phase III randomized trial, Xeloda in Adjuvant Colorectal Cancer Treatment, demonstrated that treatment with single-agent capecitabine was equivalent to bolus 5-fluorouracil with leucovorin with respect to disease-free survival and overall survival, with significantly less diarrhea, stomatitis, neutropenia, nausea and vomiting, and alopecia. This article reviews the findings and discusses how oncology nurses can help provide effective education and monitoring for patients using oral treatment in the adjuvant setting.