Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Closed	18 and over	NCI	RTOG-8313 RTOG-83-13

Objectives

I.  Evaluate tumor control, patterns of failure, effect on the therapeutic 
ratio, and normal tissue effects of twice daily fractionation radiotherapy in 
patients with locally advanced squamous cell carcinoma of the upper 
respiratory and digestive tracts (URDT).
II.  Evaluate the influence of any region of origin of primary tumor on tumor 
control probability in patients undergoing this treatment.
III.  Evaluate the acute and chronic tolerance of URDT mucosa, cervical spinal 
cord, and salivary glands to twice daily fractionation.

Entry Criteria

Disease Characteristics:

See General Eligibility Criteria

Patient Characteristics:

See General Eligibility Criteria

General Eligibility Criteria:

Patients at least 18 years of age 
with histologically proven AJC Stage III or IV (Stage II base of tongue, 
hypopharynx, nasopharynx, or maxillary sinus) inoperable squamous cell 
carcinoma (or one of its histologic subtypes, including 
lymphoepithelioma/anaplastic) arising in the head/neck region (determination 
of specific site of origin within eligible areas is not a prerequisite).  
Patients must be medically able to withstand a course of definitive 
radiotherapy and have a Karnofsky performance status of at least 50%, adequate 
renal and hematologic function, and serum calcium within normal range.  There 
may be no prior surgery for the tumor under study except biopsy obtained from 
the primary or regional lymph nodes.  Patients treated in planned combined 
pre- or postoperative programs are excluded; however, neck dissections are 
allowed if lymph nodes become resectable (if tumor persists at the primary 
site six weeks following completion of irradiation, surgery may be performed). 
 Prior radiotherapy to the head and neck is not allowed, nor is prior 
chemotherapy.  Patients with any of the following conditions are ineligible:  
prior malignancy (other than skin cancer) unless the previous cancer was 
successfully treated surgically five years or more before the current tumor; 
clinical or radiographic evidence of metastases below the clavicle; or 
simultaneous primaries (unless both tumors are squamous in type, located 
within the head and neck area, and meet all criteria for eligibility).

Expected Enrollment

The total number of patients required for study will depend on the dose at 
which toxicity is the limiting factor.  A maximum of 254 patients will be 
accrued over 26 to 35 months.  As of an April 1987 notification, accrual 
objectives have been revised to require at least 100 patients entered per arm. 
 As of June 1987, the accrual to Arms I to IV is 70, 119, 127, and 104, 
respectively.  Assuming 141 patients are needed and using the current 1:2 
randomization to Arms II and IV, a total accrual of 196 patients is necessary. 
 Using the average monthly accrual of 10.25 since the activation of Arm IV, 
this study is expected to achieve its accrual goals by November 1987.  Once 
accrual is achieved, an additional 12 months of followup will be needed to 
evaluate late complications.

Outline

Randomized study.  All patients are treated to a dose of 50.4 Gy on Regimen A; 
patients are randomized to one of the open arms for a boost dose to a reduced 
field (randomization subsequent to the start of irradiation is permitted if 
Radiotherapy has been administered for no more than 3 days and all treatment 
has been administered according to protocol specifications).  An escalating 
dose design will be used, with initial randomization to Arms I, II, and III 
with a 1:1:2 weighting in favor of Arm III.  If evaluation shows the higher 
dose to have acceptable toxicity, the lowest dose arm will be closed, the next 
arm opened, and patients randomized with a 1:1:2 weighting in favor of the 
highest dose arm.  The process of escalation will continue until unacceptable 
toxicity levels are reached or until a dose of 86.40 Gy has been tested and 
found acceptable.  As of February 1986, Arms I and III are closed, and 
patients are randomized to Arms II and IV with a 1:2 weighting in favor of Arm 
IV; Arm V is not yet open.
Regimen A:  Radiotherapy.  Irradiation of the primary and regional nodes using 
Co60 or greater energy equipment with effective photon energies of 1.25 to 45 
MeV or electron energies of 4 to 25 MeV.
Arm I:  Radiotherapy.  Boost irradiation of the primary tumor to a total of 
67.20 Gy. Arm II:  Radiotherapy.  Boost irradiation of the primary tumor to a 
total of 72.00 Gy. Arm III:  Radiotherapy.  Boost irradiation of the primary 
tumor to a total of 76.80 Gy. Arm IV:  Radiotherapy.  Boost irradiation of the 
primary tumor to a total of 81.60 Gy. Arm V:  Radiotherapy.  Boost irradiation 
of the primary tumor to a total of 86.40 Gy.

Cox JD, Pajak TF, Marcial VA, et al.: Dose-response for local control with hyperfractionated radiation therapy in advanced carcinomas of the upper aerodigestive tracts: preliminary report of radiation therapy oncology group protocol 83-13. Int J Radiat Oncol Biol Phys 18 (3): 515-21, 1990.[PUBMED Abstract]

Cooper JS, Farnan NC, Asbell SO, et al.: Recursive partitioning analysis of 2105 patients treated in Radiation Therapy Oncology Group studies of head and neck cancer. Cancer 77 (9): 1905-11, 1996.[PUBMED Abstract]

Fu KK, Cox JD, Pajak TF: In response to bentzen and thames: regarding dose-response relationships for late radiation effects in the head and neck; an analysis of RTOG 83-13 trial. Int J Radiat Oncol Biol Phys 34(2): 524-525, 1996.

Cooper JS, Farnan NC, Asbell SO, et al.: A comparison of RPA-derived and AJC staging in head and neck cancers based on RTOG data. [Abstract] Int J Radiat Oncol Biol Phys 32 (suppl 1): A-2026, 275, 1995.

Fu KK, Cox JD: Late effects of hyperfractionated-radiotherapy for head and neck cancer--in response to Drs. Withers and Taylor, IJROBP 32:887-888; 1995. Int J Radiat Oncol Biol Phys 32 (4): 1266, 1995.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Radiation Therapy Oncology Group

James Cox, MD, Protocol chair		Ph: 713-563-2316; 800-392-1611