5-fluorouracil recurrent

Colorectal cancer is the third most common cancer and the second leading cause of cancer-related deaths in the United States. (77). The incidence is approx. 40 per 100,000 in men and 25-30 per 100,000 in women (78). For those with stage 111 disease with presumed micrometastatic disease, adjuvant chemotherapy is used, typically 5-fluorouracil (5-FU) and leucovorin for 6-8 mo, with a 30% reduction in disease recurrence and 22-32% reduction in mortality (79,80). 

Mahjoubi M, Sadek H, Francois E, et al. Epidermoid anal canal carcinoma (EACC) activity of cisplatin and continuous 5 -fluorouracil in metastatic and/or local recurrent disease. Proc Annu Meet Am Soc Clin Oncol 1990 9 114. 

Kish JA, Weaver A, Jacobs J, et al. Cisplatin and 5-fluorouracil infusion in patients with recurrent and disseminated epidermoid cancer of the head and neck. Cancer 1984 53 1819-1824. 

Schrijvers D, Johnson J, Jiminez U, et al. Phase III trial of modulation of cisplatin/fluorouracil chemotherapy by interferon alfa-2b in patients with recurrent or metastatic head and neck cancer. Head and Neck Interferon Cooperative Study Group. J Clin Oncol 1998 16 1054-1059. 

Murphy B, Li Y, Celia D, et al. Phase III study comparing cisplatin (C) and 5-Fluorouracil (F) versus cisplatin and paclitaxel (T) in metastatic/recurrent head and neck cancer (MHNC). ProcAnnu Meet Am Soc Clin Oncol 2001 20 A894. 

Khuri FR, Nemunaitis J, Ganly I, et al. A controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer. Nat Med 2000 6 879-885. 

Landoni F, Maneo A, Zanetta G, et al. Concurrent preoperative chemotherapy with 5-fluorouracil and mitomycin C and radiotherapy (FUMIR) followed by limited surgery in locally advanced and recurrent vulvar carcinoma. Gynecol Oncol 1996 61 321-327. 

Clinical Use. Levamisole (Ergamisol) is primarily used to treat colorectal carcinoma. Specifically, this drug is administered with fluorouracil (see Chapter 36) to prevent recurrence of colorectal cancer after surgical removal of the primary tumor.1... 

Levamisole was first synthesized for the treatment of parasitic infections. Later studies suggested that it increases the magnitude of delayed hypersensitivity or T cell-mediated immunity in humans. In immunodeficiency associated with Hodgkin s disease, levamisole has been noted to increase the number of T cells in vitro and to enhance skin test reactivity. Levamisole has also been widely tested in rheumatoid arthritis and found to have some efficacy. However, it has induced severe agranulocytosis (mainly in HLA-B27-positive patients), which required discontinuation of its use. The drug may also potentiate the action of fluorouracil (5-FU) in adjuvant therapy of colorectal cancer, and this combination has been approved for clinical use in the treatment of Dukes class C colorectal cancer after surgery. Its use in these cases reduces recurrences, and the mechanism... 

The neurotoxicity is usually reversible by withdrawing fluorouracil. Since there is no cumulative effect, therapy can be resumed later if desired, usually with either a lower dose or a less frequent dosing schedule to prevent recurrence. 

Ankyloblepharon (adherence of the eyelids resulting in narrowing of palpebral apertures) was reported in a 59-year-old man during fluorouracil therapy for metastatic adenocarcinoma of the stomach (74). It appeared that bilateral conjunctival ulcers, secondary to fluorouracil and ulcerative blepharitis, resulted in ankyloblepharon. Withdrawal of chemotherapy resulted in improvement and re-initiation of therapy resulted in recurrence of ocular lesions. 

QUASAR was a study of the effects of a higher dose of leucovorin or the addition of levamisole to 5-fluorouracil and leucovorin on survival in 4927 patients with colorectal cancer with no evidence of residual disease after resection (14). High-dose leucovorin was not associated with a survival or recurrence benefit compared with low-dose leucovorin. The addition of levamisole had no apparent survival benefit compared with placebo, with slightly more deaths in patients assigned to levamisole than placebo. Tumor recurrences were also higher in those who took levamisole. Dermatological adverse effects were significantly more frequent in those who took levamisole compared with placebo. 

Fluorouracil (370 mg/m ) plus high-dose (175 mg) or low-dose (25 mg) folinic acid and either active or placebo levamisole has been evaluated in 4927 patients with colorectal cancer (23). Levamisole produced a significant excess of adverse dermatological events. Serious unexpected adverse events were rare. The authors concluded that the inclusion of levamisole in chemotherapy regimens for colorectal cancer does not delay recurrence or improve survival. 

There is currently no definitive role for adjuvant XRT in colon cancer because most recurrences are extrapelvic and occur in the abdomen. Although local recurrence and debilitating pelvic pain are uncommon, a subset of patients with T3 or T4 tumors located in the cecum, hepatic and splenic flexures, and sigmoid are at increased risk of local recurrence and may benefit from postoperative XRT and chemotherapy. Early trials using effective doses of whole abdominal XRT were limited by considerable toxicity. However, results from studies combining abdominal XRT plus fluorouracil are promising. To date, postoperative local XRT may reduce the risk of local recurrence and improve survival compared to adjuvant chemotherapy alone, but should only be considered for select patients with colon cancer. ... 

Investigational Approaches. Despite the significant reduction in cancer recurrence and increased survival afforded with fluorouracil-based adjuvant chemotherapy, the results obtained thus far indicate need for continued improvement. Several strategies are underway, including protracted fluorouracil infusion, oral fluorinated pyrimidines, irinotecan, oxaliplatin, and immunotherapy-based therapies. ... 

The Mayo/NCCTG trial compared postoperative XRT alone, postoperative XRT with concurrent fluorouracil plus semustine chemotherapy, and pre- and postirradiation chemotherapy in a similar population of 204 patients with rectal cancer. This was the first randomized trial in which one cycle of combination chemotherapy was given before and after XRT in addition to the administration of fluorouracil during XRT. The use of combined chemotherapy and XRT significantly affected local recurrence, relapse-free survival, and OS as compared to XRT alone. Patients receiving combined therapy experienced an overall relative reduction of recurrence of 34% at... 

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