Capecitabine Leucovorin

Capecitabine is an oral prodrug of 5-FU that also is effective in the adjuvant setting and is being evaluated as a replacement for 5-FU for patient convenience and safety reasons. Data suggest that capecitabine is at least equivalent to 5-FU and leucovorin in efficacy and is better tolerated by patients.24 Consequently, most practitioners feel that capecitabine is an acceptable alternative to IV 5-FU plus leucovorin. However, the role of capecitabine with additional chemotherapy agents such as oxaliplatin requires further study... 

Capecitabine or 5-fluorouracil plus leucovorin with or without bevacizumab... 

FU/leucovorin regimens currently have limited use but are acceptable options in patients who cannot receive oxaliplatin and are unable to tolerate oral capecitabine. 

Capecitabine monotherapy is suitable for first-line therapy in patients not likely to tolerate IV chemotherapy. Capecitabine produced superior response rates and comparable survival compared with 5-FU and leucovorin in a pooled analysis. Capecitabine is being evaluated in combination with irinote-can or oxaliplatin. 

CapOx Fluorouradl plus leucovorin only Oxaliplatin 130 mg/m2 day 1 plus capecitabine 850 mg/m2 twice a day for 14 days, repeat every 3 weeks Diarrhea, hand-foot syndrome, neuropathies... 

This benefit comes at a cost of significant toxicity, particularly neuropathic, and more mature data are necessary to demonstrate the ultimate benefit of adjuvant therapies on improved overall survival. So far irinotecan plus 5-FU based therapy has produced disappointing results in adjuvant treatment. Despite the present lack of data addressing overall survival benefit, oxaliplatin plus 5-FU/leucovorin is widely recommended as the gold standard adjuvant therapy for stage 3 disease. For those whose medical fitness or other contra-indications preclude oxaliplatin based therapy 5-FU/leucovorin on a weekly or monthly schedule is recommended. Oral capecitabine for 6 months has recently been reported to be at least equivalent to 5-FU/leucovorin. 

From Ref. (85). Abbreviations 5-FU/LV (5-fluorouracil plus leucovorin) CapeOx (capecitabine plus oxaliplatin) FOLFIRI (infusional 5-FU/LV plus irinotecan) FOLFOX (infusional 5-FU/LV plus oxaliplatin). 

Van Cutsem E, Twelves C, Cassidy J et al. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer results of a large phase III study. J Clin Onco/2001 19 4097 106. 

Two Phase III clinical studies of orally administered capecitabine in over 1,200 patients with untreated metastatic colorectal cancer demonstrated at least equal efficacy and improved tolerability versus the Mayo Clinic regimen of intravenous 5-fluorouracil/leucovorin administration. The overall response rate for patients taking capecitabine orally was 21%, versus 14% for the intravenous 5-FU/leucovorin regimen. A median 53-month follow-up revealed a three-year disease-free survival rate of 66% for capecitabine versus 63% for 5-FU/leucovorin patients. International Phase II trials also demonstrated therapeutic benefits of capecitabine monotherapy for women with metastatic breast cancer that was either resistant to both paclitaxel and anthracycline therapy. Orally administered at the twice-daily 1,250 mg/m2 regimen (cycles of two weeks of therapy followed by a week of rest), the tumor response rate was in the range of 20-25%. In addition, combination of capecitabine with a taxane yielded a unique survival benefit compared to the previous standard of taxane monotherapy for anthracycline-resistant breast cancer.13,14... 

Warfarin—(major interaction), results in increased anticoagulant effects, increased risk of bleeding monitor coagulation parameters closely phenytoin—may require phenytoin dose reduction monitor phenytoin levels closely leucovorin increases the activity and toxicity of capecitabine... 

Upon disease progression following standard initial therapy, appropriate treatment options may include oxaliplatin plus fluorouracil and leucovorin, irinotecan plus cetuximab, cetuximab, irinotecan, continuous-infusion fluorouracil, capecitabine plus irinotecan or... 

Cassidy J, Dirix L, Bissett D, Reigner B, Griffin T, Allman D, Osterwalder B, Van Oosterom AT. A phase I study of capecitabine in combination widi oral leucovorin in patients with intractable solid tumours. Clin CcmcerRes ( 99 4, 2755-61. 

Capecitabine is a tumor-selective oral fluoropyrimidine. It has been approved by the FDA and NICE for the treatment of colorectal cancer in both the adjuvant and metastatic settings and for patients with breast cancer after anthracycline and taxane therapy [93 ,94 ]. It has also been approved by NICE for advanced gastric cancer as part of platinum-based therapy [95 ]. In a randomized phase III study of adjuvant capecitabine versus fluorouracil -I- leucovorin, efficacy was similar between the groups but grade 3/4 adverse reactions were significantly less common in those who were given capecitabine [96 ]. The starting dose is usually 1000-1250 m m bd for 14 days, followed by 7 days rest. 

Skin Hand-foot syndrome is significantly more common with capecitabine than fluorouracil-I-leucovorin, perhaps because of more prolonged drug exposure [104 ]. It is characterized by painless or painful swelling, erythema, and desquamation of the palms and soles. It affects 54% of patients (any grade) and is severe in 17% [102 ]. Dosage modification may be required. 

Susceptibility factors Age Multivariate analysis from a large safety analysis of two randomized phase III studies of capecitabine versus fluorouracil- -leucovorin showed that any increase in toxicity in older patients is mainly due to an age-related reduction in renal function [102 ]. However, special care should be taken with patients over 80 years of age [104 ]. 

Capecitabine Derivative of 5-fluorouracil Colorectal, pancreatic, metastatic breast, stomach Prodrag form of 5-fluorouracil Acral erythema erythema palmar-plantar keratoderma exfol. dermatitis St CV GI hematolc ic cytopenias Not to be used with leucovorin... 

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