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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Completed	any age	NCI	SWOG-8892 EST-2388, RTOG-8817, INT-0099

Objectives

I.  Compare, in a multi-institutional Phase III setting, CR rate, time to 
treatment failure, overall survival, and patterns of recurrence among patients 
with Stage III/IV nonmetastatic carcinoma of the nasopharynx randomly assigned 
to treatment with radiotherapy alone vs. radiotherapy with concurrent 
cisplatin followed by cisplatin/fluorouracil.

II.  Compare the qualitative and quantitative toxicities of these two 
treatment regimens.

Entry Criteria

Disease Characteristics:

Histologically proven carcinoma of the nasopharynx
  No prior or concurrent adenocarcinoma

Previously untreated Stage III/IV (M0) disease

At least 1 bidimensionally measurable lesion required, with diagrams made of
primary and nodal metastases by CT or MRI of nasopharynx, base of skull, and
cervical/supraclavicular lymph node-bearing regions with 28 days of entry

No lung, bone, or liver metastases by the following procedures:
  Chest x-ray within 42 days of entry

  Liver and bone scans (if alkaline phosphatase or SGOT is elevated or if
  clinically indicated) within 42 days of entry

Examination of oral cavity, oropharynx, and larynx by a multimodal team
required, including dental care analysis

Concurrent registration on SWOG-8855 (flow cytometry protocol) allowed

Prior/Concurrent Therapy:

Biologic therapy:
  Not specified

Chemotherapy:
  No prior chemotherapy

Endocrine therapy:
  Not specified

Radiotherapy:
  No prior radiotherapy except for nonmelanomatous skin cancer outside the
  planned radiotherapy treatment volumes

Surgery:
  No prior surgery to the primary site or nodes (except diagnostic)
  No resection following completion of protocol treatment except for the
     removal of persistent neck nodes

Patient Characteristics:

Age:
  Any age

Performance status:
  SWOG 0-2 (Karnofsky 50-100%)

Life expectancy:
  At least 6 months

Hematopoietic:
  WBC at least 4,000
  AGC at least 2,000
  Platelets at least 100,000

Hepatic:
  Liver and bone scans required if alkaline phosphatase or SGOT are elevated

Renal:
  Creatinine no more than 1.6 mg/dl OR
  Creatinine clearance at least 60 ml/min

Other:
  No second malignancy within 5 years except:
     Basal cell skin cancer
     Carcinoma in situ of the cervix
  No pregnant or nursing women
  Effective contraception recommended for fertile women

Expected Enrollment

270 patients will be randomized over 4.5-5.4 years.

Outline

Randomized study.

Arm I:  Radiotherapy.  Irradiation of primary nasopharyngeal site and neck 
nodes using megavoltage equipment with energies of Co60 or greater.

Arm II:  Radiotherapy plus Concurrent Single-Agent Chemotherapy followed by 
2-Drug Combination Chemotherapy.  Radiotherapy as in Arm I; plus Cisplatin, 
CDDP, NSC-119875; followed by CDDP; Fluorouracil, 5-FU, NSC-19893.

Low WK, Toh ST, Wee J, et al.: Sensorineural hearing loss after radiotherapy and chemoradiotherapy: a single, blinded, randomized study. J Clin Oncol 24 (12): 1904-9, 2006.[PUBMED Abstract]

Wee J, Tan EH, Tai BC, et al.: Randomized trial of radiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy in patients with American Joint Committee on Cancer/International Union against cancer stage III and IV nasopharyngeal cancer of the endemic variety. J Clin Oncol 23 (27): 6730-8, 2005.[PUBMED Abstract]

Bahl M, Siu LL, Pond GR, et al.: Tolerability of the Intergroup 0099 (INT 0099) regimen in locally advanced nasopharyngeal cancer with a focus on patients' nutritional status. Int J Radiat Oncol Biol Phys 60 (4): 1127-36, 2004.[PUBMED Abstract]

Al-Sarraf M, Le Blanc M, Giri P, et al.: Superiority of five year survival with chemo-radiotherapy (CT-RT) vs radiotherapy in patients with locally advanced nosapharyngeal cancer (NPC). Intergroup (0099) (SWOG 8892, RTOG 8817, ECOG 2388 phase III study: final report. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-905, 227a, 2001.

Ensley JF, Youssef E, Kim H, et al.: Locally advanced nasopharyngeal cancer. Curr Treat Options Oncol 2(1): 15-23, 2001.

Al-Sarraf M, LeBlanc M, Giri PG, et al.: Chemo-radiotherapy(CT-RT) vs radiotherapy (RT) in patients (PTS) with locally advanced nasopharyngeal cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 17: A1483, 385a, 1998.

Al-Sarraf M, LeBlanc M, Giri PG, et al.: Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol 16 (4): 1310-7, 1998.[PUBMED Abstract]

Al-Sarraf M, LeBlanc M, Giri PG, et al.: Superiority of chemoradiotherapy (CT-RT) vs. radiotherapy (RT) in patients (pts) with locally advanced nasopharyngeal cancer (NPC). Preliminary results of intergroup (0099) (SWOG 8892, RTOG 8817, ECOG 2388) randomized study. [Abstract] Proceedings of the American Society of Clinical Oncology 15: A-882, 313a, 1996.

Al-Sarraf M, LeBlanc M, Giri PGS, et al.: Improved overall survival with chemo-radiotherapy (CT-RT) vs radiotherapy (RT) in patients with locally advanced nasopharyngeal cancer (NPC). Preliminary results of intergroup (0099) (SWOG 8892, RTOG 8817, ECOG 2388) randomized study. [Abstract] Proceedings of the International Conference on Head and Neck Cancer A240, 118, 1996.

Giri PG, Shankar LM, Al-Sarraf M, et al.: Improved survival with chemotherapy and radiation therapy versus radiation therapy alone in advanced nasopharyngeal cancer. Preliminary results of an intergroup randomized trial. INT 0099, SWOG 8892, RTOG 8817, ECOG 2388. [Abstract] Int J Radiat Oncol Biol Phys 36 (suppl 1): A-8, 162, 1996.

Trial Contact Information

Trial Lead Organizations

Southwest Oncology Group

Muhyi Al-Sarraf, MD, FRCPC, FACP, Protocol chair(Contact information may not be current)		Ph: 248-849-3541; 800-341-0801 Email: mealsarraf@aol.com

Eastern Cooperative Oncology Group

George Adams, MD, Protocol chair(Contact information may not be current)		Ph: 612-624-8484; 888-226-2376

Radiation Therapy Oncology Group

Jay Cooper, MD, FACR, FACRO, Protocol chair(Contact information may not be current)		Ph: 212-263-6485 Email: jay.cooper@med.nyu.edu