Radiation 5-fluorouracil

Adjuvant therapy consisting of 5-fluorouracil-based chemotherapy in combination with radiation therapy should be offered to patients with stage II or III cancer of the rectum. 

RT = radiation, EF = extended fields, C = cisplatin, 5FU = 5 fluorouracil, TAH = extrafascial hysterectomy, HU = hydroxyurea. 

Cummings B J, Keane TJ, O Sullivan B, et al. Epidermoid anal cancer treatment by radiation alone or by radiation and 5-fluorouracil with and without mitomycin C. Int J Rad One Biol Phys 1991 21(5) 115-125. 

An ideal radiosensitizer would be the one that can maximize radiation therapy benefit, can be easily administered, can be optimally sequenced with radiation therapy for best effects, and have no overlapping toxicities with radiation. Although falling short in certain of these characteristics, 5-fluorouracil (5-FU) has become the most promising clinical radiosensitizer in combined chemoradiotherapy regimens. 

The mechanisms of interaction between fluorouracil and radiation are not clearly understood. Different hypotheses have been postulated to explain the synergistic or potentiated effect of 5-FU with radiation including redistribution of cells to a more radiosensitive cell cycle phase, deranged pyrimidine pools with reduced capacity for repair of DNA damage, and activation of apoptosis. The effect of 5-FU on radiation damage also appears to vary in different cell lines, thus complicating the extrapolation of laboratory results into clinical practice. 

The feasibility of concomitant chemoradiotherapy has been evaluated in numerous studies in esophageal cancer, given either as preoperative treatment or as primary therapy. In most of these studies, fluorouracil was an integral part of the chemotherapy regimen. Byfield et al. (74) evaluated the efficacy of 5-FU infusion (for 5 d) and 10 Gy of radiation... 

In another GITSG study, patients with locally unresectable pancreatic cancer were randomized to multidrug chemotherapy (streptozocin, CMT, and fluorouracil) or to 54 Gy of radiation plus fluorouracil followed by the same three-drug chemotherapy regimen. Overall survival for the combined chemoradiotherapy group was superior, i.e., 41% at one year vs 19% for the chemotherapy group (79). 

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. 

Byfield JE, Sharp TR, Tang S, et al. Phase I and II trial of cyclical 5-day infused 5-fluorouracil and coincident radiation in advanced cancer of the head of neck. J Clin Oncol 1983 2 406-413. 

Byfield JE. Theoretical basis and clinical applications of 5-fluorouracil used as a radiosensitizer. In Rosenthal CJ, Rothman M (eds) Clinical Applications of Continuous Infusion Chemotherapy and Concomitant Radiation Therapy, Plenum Publishing Corp. New York, 1986, pp. 113-125. 

Flam MS, John JM, Pajak T, et al. Radiation (RT) and 5-fluorouracil (5-FU) vs radiation, 5-FU, mitomycin-C (MMC) in the treatment of anal carcinoma results of a phase III randomized RTOG/ ECOG intergroup trial. Proc Annu Meet Am Soc Clin Oncol 1995 14 191. Abstract A443. 

Martenson JA, Lipitz S, Wagner H, et al. Phase II trial of radiation therapy, 5-fluorouracil and cisplatin in patients with anal cancer. Int J Radiat Oncol Biol Phys 1995 32(suppl 1) 158. 

The earliest combination chemotherapy and radiation trials in nonsmall-cell lung cancer included cisplatin and 5-fluorouracil and concurrent radiation therapy and found survival results comparable to those for sequential chemotherapy and radiation or to daily cisplatin and radiation therapy without surgery (119,121). Phase II studies of stage Ilia and Illb nonsmall-cell lung cancer patients treated with the combination of cisplatin with etoposide and 5 -fluorouracil and either single daily radiation fractionation or twice daily radiation fractionation prior to surgery produced similar clinical results (119,121). Complete surgical resection was accomplished in 70% of the patients, the median survival was 22 mo and the 2-yr survival rate was 45%. 

Weiden PL, Piantodosi S. Preoperative chemotherapy cisplatin and fluorouracil and radiation therapy in stage III non-small cell lung cancer A phase II study of the Lung Cancer Study Group. JNatl Cancer Oust 1991 83 266-272. 

Kaufman DS, Winter KA, Shipley WU, et al. The initial results in muscle-invading bladder cancer of RTOG 95-06 phase Ell trial of transurethral surgery plus radiation therapy with concurrent cisplatin and 5-fluorouracil fohowed by selective bladder preservation or cystectomy depending on the initial response. The Oncologist 2000 5 471 —476. 

Wright et al. from the Massachusetts General Hospital reported interesting results from their intensive trial of preoperative paclitaxel, cisplatin, and 5-fluorouracil with hyperfractionated radiation (total tumor dose of 58.5 Gy and 45 Gy to the mediastinum)... 

Meluch AA, Hainsworth JD, Gray JR, et al. Preoperative combined modality therapy with paclitaxel, carboplatin, prolonged infusion 5-fluorouracil, and radiation therapy in localized esophageal cancer preliminary results of a Minnie Pearl Cancer Research Network phase II trial. Cancer J Sci Am 1999 5 (2) 84-91. 

Kies ME, Haraf D, Rosen F, Stenson K, List M, Brockstein B, Chung T, Mittal B, Pelzer H, Portugal L, Rademaker A, Weichselbaum R, Vokes EE. Concomitant Infusional Paclitaxel and Fluorouracil, Oral Hydroxyurea, and Hyperfractionated Radiation for Locally Advanced Squamous Head and Neck Cancer. J Clin Oncol 2001 19 1961-1969. 

Table 1 Factors Affecting 5-FU (5-fluorouracil) and CPT-11 (Irinotecan) Radiation Sensitization ...

Rich TA. Irradiation Plus 5-Fluorouracil Cellular Mechanisms of Action and Treatment Schedules. Semin Radiat Oncol 1997 7(4) 267-273. 

Lo TC, Wiley AL, Ansfield FJ, et al. Combined radiation therapy and 5-fluorouracil for advanced squamous cell carcinoma of the oral cavity and oropharynx a randomized study. Am J Roentgenol 1976 126 229-235. 

Keane TJ, Cummings B J, O Sullivan B, et al. A randomized trial of radiation therapy compared to split course radiation therapy combined with mitomycin C and 5 fluorouracil as initial treatment for advanced laryngeal and hypopharyngeal squamous carcinoma. Int J Radiat Oncol Biol Phys 1993 25 613-618. 

Adelstein DJ, Adams GL, Li Y. A phase III comparison of standard radiation therapy (RT) versus RT plus concurrent cisplatin (DDP) versus split-course RT plus concurrent DDP and 5-fluorouracil (5FU) in patients with unresectable squamous cell head and neck cancer (SCHNC), ProcAnnu Meet Am Soc Clin Oncol 2000 19 A 1624. 

Byfield JE, Calabro-Jones P, Klisak I, et al. Pharmacologic requirements for obtaining sensitization of human tumor cells in vitro to combined 5-Fluorouracil or Florafur and X rays. Int J Radiat Oncol Biol Phys 1982 8 1923-1933. 

Kies MS, Haraf DJ, Rosen F, etal. Concomitant infusional paclitaxel and fluorouracil, oral hydroxyurea, and hyperfractionated radiation for locally advanced squamous head and neck cancer. J Clin Oncol 2001 19 1961-1969. 

Taylor SG, Murthy AK, Vannetzel JM, et al. Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer. J Clin Oncol 1994 12 385-395. 

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