Hyperfractionated radiotherapy

The RTO G trial R0102 is no w open for patient accrual and will be a randomized Phase II comparison of 5-FU infusion plus irinotecan and conventionally fractionated radiotherapy to a dose of 50.4 Gy (Table 2). This will be compared to a hyperfractionated radiotherapy arm given in conjunction with protracted venous infusion of 5-FU. Readers interested in participating should contact the radiotherapy oncology group headquarters in Philadelphia, PA. 

Based on this initial study by Rischin et al., the University of Chicago is currently accruing for a phase I trial of previously irradiated patients. Patients will receive standard daily radiotherapy and tirapazamine (wk 1-3) combined with cisplatin (wk 3 and 5), converting to hyperfractionated radiotherapy for wk 4—6. 

Wright CD, Wain JC, Lynch TJ, et al. Induction therapy for esophageal cancer with paclitaxel and hyperfractionated radiotherapy a phase I and II study. J Thorac Cardiovasc Surg 1997 114(5) 811-815. 

Kinsella, T. J., Collins, J., Rowland, J. et al. 1988. Pharmacology and phase I/II study of continuous intravenous infusions of iododeoxyuridine and hyperfractionated radiotherapy in patients with glioblastoma multiforme. J. Clin. Oncol., 6, 871-9. 

Payne DG, Simpson WJ, Keen C, Platts ME. Malignant astrocytoma hyperfractionated and standard radiotherapy with chemotherapy in a randomized prospective clinical trial. Cancer 1982 50 2301-2306. 

The median follow-up was 23 mo for the 1073 evaluable patients. Patients that received hyperfractionated or accelerated radiation therapy with boost had increased locoregional control (p = 0.045 and p = 0.05, respectively) and a trend toward improved disease-free survival (DFS) (p = 0.067 and p = 0.054, respectively) in comparison to conventional radiation therapy. However, there was no improvement in overall survival(s). Patients given accelerated split-course fractionation had similar outcomes to those who had received conventional radiotherapy. Hyperfractionated radiation therapy is the method of choice for combined chemoradiotherapy in current investigative approaches for head and neck cancer. 

We are also currently conducting a phase I/II trial in patients with unresectable, advanced, or locally recurrent HNC with potential benefits from reirradiation (Table 4). We chose to evaluate the promising radio sensitization effects of irinotecanby combining it with our FHX regimen (79). Patients were given five cycles of irinotecan (5-15 mg/m2, d 1-5), continuous infusion 5-FU (600 mg/m2, d 1-5), hydroxyurea (500 mg BID for 11 doses), and hyperfractionated twice-daily radiotherapy. Preliminary analysis of patients in the phase I setting established a MTD of irinotecan at 10 mg/m2. 

Horiot JC, Le Fur R, N Guyen T, et al. Hyperfractionation versus conventional fractionation in oropharyngeal carcinoma final analysis of a randomized trial of the EORTC cooperative group of radiotherapy. Radiother Oncol 1992 25 231-241. 

Fu KK, Pajak TF, Trotti A, et al. A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas first report of RTOG 9003. lnt J Radiat Oncol Biol Phys 2000 48 7-16. 

Saunders MI, Dische S, Barrett A, et al. Continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy in non-small cell lung cancer. A randomized multicentre trial. Lancet 1997 350 161-165. 

Bonner JA, McGinnis WL, Stella PJ, et al. The possible advantage of hyperfractionated thoracic radiotherapy in the treatment of locally advanced non-small cell lung carcinoma Results of the North Central Cancer Treatment Study Group Phase III trial. Cancer 1998 82 1037-1048. 

Eberhardt W, Wilke H, Stamatis G, et al. Preoperative chemotherapy followed by concurrent chemoradiation therapy based on hyperfractionated accelerated radiotherapy and definitive surgery in locally advanced non-small cell lung cancer. Mature results of a phase II trial. J Clin Oncol 1998 16 622-634. 

Glisson B, Scott C, Komaki R, et al. Cisplatin, Ifosfamide, prolonged oral etoposide and concurrent accelerated hyperfractionated thoracic radiotherapy for patients with limited small-cell lung cancer results of RTOG 93-12 (abstract 1733). Proc Am Soc Clin Oncol 1998 17 450a. 

Budach V, Stuschke M, Budach W, et al (2005) Hyperfraction-ated accelerated chemoradiation with concurrent fluo-rouracil-mitomycin is more effective than dose-escalated hyperfractionated accelerated radiation therapy alone in locally advanced head and neck cancer final results of the radiotherapy cooperative clinical trials group of the German Cancer Society 95-06 Prospective Randomized Trial. J Clin Oncol 23 1125-1135... 

Awwad HK, Lotayef M, Shouman T, et al (2002) Accelerated hyperfractionation (AHF) compared to conventional fractionation (CF) in the postoperative radiotherapy of locally advanced head and neck cancer influence of proliferation. BrJ Cancer 86 517-523... 

Budach W, Hehr T, Budach V, et al (2006) A meta-analysis of hyperfractionated and accelerated radiotherapy and combined chemotherapy and radiotherapy regimens in unresected locally advanced squamous cell carcinoma of the head and neck. BMC Cancer 6 28... 

Bourhis J et al. (2006) Hyperfractionated or accelerated radiotherapy in head and neck cancer a meta-analysis. Lancet... 

Buffa FM et al. (2004) Molecular marker profiles predict locoregional control of head and neck squamous cell carcinoma in a randomized trial of continuous hyperfractionated accelerated radiotherapy. Clin Cancer Res 10(ll) 3745-3754... 

Sheldon PW et al. (1974) The incidence of lung metastases in C3H mice after treatment of implanted solid tumors with X-rays or surgery. Br J Cancer 30(4) 342 348 SRC Trial Group (1997) Improved survival with preoperative radiotherapy in resectable rectal cancer. Swedish Rectal Cancer Trial. N Engl J Med 336(14) 980-987 Stausbol-Gron B, Overgaard J (1999) Relationship between tumor cell in vitro radiosensitivity and clinical outcome after curative radiotherapy for sqiuimous cell carcinoma of the head and neck. Radiother Oncol 50(l) 47-55 Stuschke M, Thames HD (1999) Fractionation sensitivities and dose-control relations of head and neck carcinomas analysis of the randomized hyperfractionation trials. Radiother Oncol 51(2) 113-121... 

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