Cancer leucovorin

Fluorouracil (5-FU) is the most widely used chemotherapeutic agent for colorectal cancer. Leucovorin (folinic acid) is usually added to 5-FU as a biochemical modulator to improve response rates. 

Breast cancer leucovorin 20 mg/m, days 1-5, every 4-5 weeks myelosuppression... 

MTX is part of curative therapeutic schedules for acute lymphoblastic leukemias (ALL), Burkitt s lymphoma, and choriocarcinoma. It was also used in adjuvant therapy of breast cancer. High dose MTX with leucovorin rescue can induce about 30% remissions in patients with metastatic osteogenic sarcoma. MTX is one of the few antineoplastic drugs that can be safely administered intrathecally for the treatment of meningeal metastases and leukemic infiltrations (routine prophylaxis in ALL). In addition, MTX can be used as an immunosuppressive agent for the treatment of severe rheumatoid arthritis and psoriasis. 

The clinical trial that resulted in FDA approval of bevacizumab (February 2004) was a randomized, double-blind, phase III study in which bevacizumab was administered in combination with bolus-IFL (irinotecan, 5FU, leucovorin) chemotherapy as first-line therapy for previously untreated metastatic colorectal cancer [3]. Median survival was increased from 15.6 months in the bolus-IFL + placebo arm to 20.3 months in the bolus-IFL + bevacizumab arm. 

Flurouracil-based chemotherapy is the standard regimen used in adjuvant treatment of colon cancer. It is usually given for 6 months with leucovorin, and based on recent clinical trials, oxaliplatin also may be added to the combination. 

Andre T, Boni C, Mounedji-Boudiaf L, et al. Oxaliplatin, fluo-rouracil, leucovorin as adjuvant treatment for colon cancer. New Engl J Med 2004 350 2243-2351. 

Goldberg RM, Sargent DJ, Morton RF, et al. A randomized, controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 2004 22 23-30. 

Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. New Engl J Med 2004 350 2335-2342. 

Saltz LB, Cox JV, Blanke C et al. Irino-tecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med 2000 343 905-914. 

Leichman CG, Lenz HJ, Leichman L et al. Quantitation of intratumoral thymidylate synthase expression predicts for disseminated colorectal cancer response and resistance to protracted-infusion fluoro-uracil and weekly leucovorin. J Clin Oncol 1997 15 3223-3229. 

The answer is c. (Katzung, pp 608-609, 932-9.13.) Methotrexate is classified as an anti metabolite with therapeutic uses in cancer chemotherapy and as an immunosuppressive agent indicated in the treatment of severe active classical rheumatoid arthritis. Leucovorin is related to methotrexate in that it is an antagonist of its actions. It can supply a source of reduced folate for the methylation reactions that are prevented by methotrexate. 

Calcium leucovorin is also identified by the National Cancer Institute number NSC 3590. 

Porschen, R. et al., Fluorouracil plus leucovorin as effective adjuvant chemotherapy in curatively resected stage III colon cancer Results of the trial adjCCA- 01, J Clin. Oncol., 19, 1787, 2001. 

Giacchetti, S. et al. Phase III multicenter randomized trial of oxaUplatm added to chronomod-ulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer,. Clin. Oncol, 18, 136-147, 2000. 

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). 

Minsky BD, Cohen AM, Kemeny N, et al. Enhancement of radiation-induced downstaging of rectal cancer by fluorouracil and high-dose leucovorin chemotherapy. J Clin Oncol 1992 10 79-84. 

Hoff PM, Pazdur R, Benner SE, Canetta R. UFT and leucovorin a review of its clinical development and therapeutic potential in the oral treatment of cancer. Anticancer Drugs 1998 9 479 490. 

Hoff PM, Janjan N, Saad Ed, et al. Phase I study of preoperative oral uracil and tegafurplus leucovorin and radiation therapy in rectal cancer. J Clin Oncol 2000 18 3529-3534. 

Vanderbilt University Medical Center has recently completed accruing patients to a Phase II study of neoadjuvant chemoradiation, which consists of preoperative paclitaxel (175 mg/m2,3-h infusion) followed by cisplatin 75 mg/m2 d 1 and 21. Concurrent radiation was given to a total dose of 3000 cGy, in 200 cGy/fraction. Patients who are resectable go on to surgery 4 wk after completion of chemoradiation, whereas those who are unresectable (i.e., cervical esophageal cancer) continue to a total dose of 60 Gy without treatment interruptions. One month following surgery, patients receive two cycles (q 21-28 d) of postoperative chemotherapy, which consists of paclitaxel 175 mg/m2 over 3 h d 1,5-FU 350 mg/m2, d 1-3, and leucovorin 300 mg d 1-3. Preliminary analysis of this... 

Blanke CD, Chiappori A, Epstein B, et al. A Phase II Trial of Neoadjuvant Paclitaxel (T) and Cisplatin (P) with Radiotherapy, Followed by Surgery (S) and Postoperativve T with 5-Fluorouracil (F) and Leucovorin (L) in Patients (pts) with Locally Advanced Esophageal Cancer (LAEC). ProcAnnu Meet Am Soc Clin Oncol 1997 16 A1006. 

Berlin J, Kubba S, Blanke CD, et al. Phase II Study of Neoadjuvant Cisplatin (P), and Taxol (T) with Concomitant Radiotherapy Followed by Surgery and then Taxol and 5FU, Leucovorin (L) in Patients with Locally Advanced Esophageal Cancer. ASCO 2000 Abstract 1246. 

Based on the successful experience in colon carcinoma, the most recent Intergroup trial (INT-0114) explored the role of biomodulation of 5-FU in rectal cancer. This four-arm trial randomized patients to pelvic irradiation and 6 mo of bolus 5-FU vs bolus 5-FU and levamisole, leucovorin, or both (30). There was no significant difference in disease-free survival and overall survival (78-80%) among the four treatment arms in a prelimi-... 

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