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

Alternate Title

Radiation Therapy With or Without Chemotherapy in Treating Patients With Advanced Cancer of the Larynx

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	18 and over	NCI	RTOG-9111 EST-R9111, SWOG-9201, NCT00002496, RTOG-91-11

Objectives

I.  Compare, in a phase III setting, overall and disease-free survival with 
preservation of laryngeal function in patients with stage III/IV squamous cell 
carcinoma of the glottic and supraglottic larynx treated with 
cisplatin/fluorouracil (CDDP/5-FU) followed by radiotherapy vs. concomitant 
radiotherapy plus CDDP vs. radiotherapy alone.

II.  Compare the tumor response after completion of chemotherapy but prior to 
initiation of radiotherapy with that following completion of radiotherapy and 
concurrent chemotherapy.

III.  Compare the patterns of relapse (local and regional recurrence and 
distant metastasis) with these treatments.

IV.  Compare the incidence of second primary tumors in patients treated on 
these three regimens.

V.  Compare the acute and chronic adverse effects of these three regimens.

VI.  Compare the morbidity experienced with neck dissection and/or laryngeal 
salvage surgery following treatment with these regimens.

VII.  Compare quality of life of patients with laryngeal preservation vs. 
patients requiring salvage laryngectomies.

VIII.  Compare the quality of life of patients receiving radiotherapy alone 
vs. those receiving chemotherapy as well.

Entry Criteria

Disease Characteristics:

Biopsy-proven, previously untreated, squamous cell carcinoma of the glottic
and supraglottic larynx that would normally require total laryngectomy

Stage III/IV disease (excluding T1 and M1)
  Endoscopic tumor staging required within 4 weeks of entry

  Tumors must be considered resectable and potentially curable with
  conventional surgery and radiotherapy

  T4 disease limited to:
     Up to 1 cm invasion of the base of tongue
     Questionable cartilage invasion on CT (clinically T3)

Measurable disease required

No synchronous primary tumors

No subglottic tumors

Prior/Concurrent Therapy:

Biologic therapy:
  No prior therapy

Chemotherapy:
  No prior therapy

Endocrine therapy:
  No prior therapy

Radiotherapy:
  No prior radiotherapy to the head and neck

Surgery:
  No prior therapy

Patient Characteristics:

Age:
  18 and over

Performance status:
  Karnofsky 60%-100%

Hematopoietic:
  (obtained within 3 weeks of entry)
  WBC at least 3,500
  Platelets at least 100,000

Hepatic:
  Not specified

Renal:
  (obtained within 2 weeks of entry)
  Creatinine clearance at least 50 mL/min (measured or calculated)
  Serum calcium normal

Cardiovascular:
  Status adequate to tolerate all protocol therapy

Pulmonary:
  Status adequate to tolerate all protocol therapy

Other:
  Nutritional status adequate to tolerate all protocol therapy
  Mental status adequate to follow instructions and keep appointments
  No second malignancy except nonmelanomatous skin cancer
     (Patients who have been disease-free for at least 3 years following
     treatment for a prior cancer may be eligible at the discretion of the
     protocol chairman)
  Negative pregnancy test required of fertile women
  Effective contraception required of fertile women

Expected Enrollment

546 patients (182/arm) will be entered over approximately 3 years.  If any arm 
is clearly inferior in laryngectomy-free survival after 137 patients have 
completed 2 years of follow-up study, that arm will be closed to further 
accrual.  A second interim analysis will be conducted after 410 patients have 
completed 2 years of follow-up.

Outline

Randomized study.  Patients on any arm, clinically staged N+ undergo neck 
dissection following completion of radiotherapy.

Arm I:  2-Drug Combination Chemotherapy followed by Radiotherapy.  Cisplatin, 
CDDP, NSC-119875; Fluorouracil, 5-FU, NSC-19893; followed by regional 
irradiation using linear accelerators with photon energies of 1.25-6 MV, 
electron energies of 8-17 MeV, or Co60.

Arm II:  Radiotherapy plus Single-Agent Chemotherapy/Radiosensitization.  
Regional irradiation using equipment as in Arm I; plus CDDP.

Arm III:  Radiotherapy.  Regional irradiation using equipment as in Arm I.

Forastiere AA, Maor M, Weber RS, et al.: Long-term results of intergroup RTOG 91-11: a phase III trial to preserve the larynx--Induction cisplatin/5-FU and radiation therapy versus concurrent cisplatin and radiation therapy versus radiation therapy. [Abstract] J Clin Oncol 24 (Suppl 18): A-5517, 284s, 2006.

Forastiere AA, Goepfert H, Maor M, et al.: Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 349 (22): 2091-8, 2003.[PUBMED Abstract]

Weber RS, Berkey BA, Forastiere A, et al.: Outcome of salvage total laryngectomy following organ preservation therapy: the Radiation Therapy Oncology Group trial 91-11. Arch Otolaryngol Head Neck Surg 129 (1): 44-9, 2003.[PUBMED Abstract]

Maor MH, Berkey B, Forastiere A, et al.: Larynx preservation and tumor control in stage III and IV laryngeal cancer: a three-arm randomized intergroup trial: RTOG 91-11. [Abstract] Int J Radiat Oncol Biol Phys 54(2 suppl 1): 2-3, 2002.

Forastiere AA, Berkey B, Maor M, et al.: Phase III trial to preserve the larynx: induction chemotherapy and radiotherapy versus concomitant chemoradiotherapy versus radiotherapy alone, Intergroup trial R91-11. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-4, 2a, 2001.

Coyne JC, Pajak TF, Bruner DW: Reply to emotional well-being does not predict survival in head and neck cancer patients: a Radiation Therapy Oncology Group study. Cancer 112 (10): 2327-8, 2008.

Machtay M, Moughan J, Trotti A, et al.: Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer: an RTOG analysis. J Clin Oncol 26 (21): 3582-9, 2008.[PUBMED Abstract]

Siddiqui F, Pajak TF, Watkins-Bruner D, et al.: Pretreatment quality of life predicts for locoregional control in head and neck cancer patients: a radiation therapy oncology group analysis. Int J Radiat Oncol Biol Phys 70 (2): 353-60, 2008.[PUBMED Abstract]

Spiegel D, Kraemer HC: Emotional well-being does not predict survival in head and neck cancer patients: a Radiation Therapy Oncology Group study. Cancer 112 (10): 2326-7; author reply 2327-8, 2008.[PUBMED Abstract]

Coyne JC, Pajak TF, Harris J, et al.: Emotional well-being does not predict survival in head and neck cancer patients: a Radiation Therapy Oncology Group study. Cancer 110 (11): 2568-75, 2007.[PUBMED Abstract]

Konski A, Bhargavan M, Owen J, et al.: The price of failure: economic analysis of recurrence and complications of patients treated on RTOG 91-11. [Abstract] The American Radium Society 89th Annual Meeting, May 5-29, 2007, Amsterdam, Netherlands. A-SS-6, 3, 2007.

O'Meara EA, Machtay M, Moughan J, et al.: Associations between radiation doses to pharyngeal regions and severe late toxicity in head and neck cancer patients treated with concurrent chemoradiotherapy: an RTOG analysis. [Abstract] Int J Radiat Oncol Biol Phys 69 (3): A-96, S54-5, 2007.

Konski AA, Bhargavan M, Owen J, et al.: The addition of chemotherapy to radiation is cost-effective in the treatment of patients with locally advanced laryngeal cancer: an economic analysis of Radiation Therapy Oncology Group (RTOG) 91-11. [Abstract] Int J Radiat Oncol Biol Phys 66 (3 Suppl 1): A-115, S66, 2006.

Machtay M, Moughan J, Trotti A, et al.: Pre-treatment and treatment related risk factors for severe late toxicity after chemo-RT for head and neck cancer: an RTOG analysis. [Abstract] J Clin Oncol 24 (Suppl 18): A-5500, 280s, 2006.

Mukherji SK, Toledano AY, Beldon C, et al.: Interobserver reliability of computed tomography-derived primary tumor volume measurement in patients with supraglottic carcinoma. Cancer 103 (12): 2616-22, 2005.[PUBMED Abstract]

Bourhis J, Amand C, Pignon JP, et al.: Update of MACH-NC (Meta-Analysis of Chemotherapy In Head & Neck Cancer ) database focused on concomitant chemotherapy. [Abstract] J Clin Oncol 12 (Suppl 14): A-5505, 489s, 2004.

Konski AA, Pajak T, Movsas B, et al.: Socio-demographic variables influence outcome in Radiation Therapy Oncology Group head and neck trials. [Abstract] Proceedings of the American Society of Clinical Oncology 22 (Suppl 14): A-6043, 529s, 2004.

Movsas B, Konski A, Pajak T, et al.: Quality of life (QOL) variables influence local regional control in Radiation Therapy Oncology Group (RTOG) headsneck trials (9003 and 9111). [Abstract] Int J Radiat Oncol Biol Phys 60 (1 Suppl 1): A-199, S252, 2004.

Trial Contact Information

Trial Lead Organizations

Radiation Therapy Oncology Group

Helmuth Goepfert, MD, Protocol chair(Contact information may not be current)		Ph: 713-792-6925; 800-392-1611 Email: hgoepfer@mdanderson.org

Eastern Cooperative Oncology Group

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

Southwest Oncology Group

David Schuller, MD, Protocol chair		Ph: 614-293-4878 Email: david.schuller@osumc.edu

Registry Information
Official Title		PHASE III TRIAL TO PRESERVE THE LARYNX: INDUCTION CHEMOTHERAPY AND RADIATION THERAPY VERSUS CONCOMITANT CHEMOTHERAPY AND RADIATION THERAPY VERSUS RADIATION THERAPY
Trial Start Date		1992-08-17
Registered in ClinicalTrials.gov		NCT00002496
Date Submitted to PDQ		1992-08-17
Information Last Verified		2008-06-23
NCI Grant/Contract Number		U10-CA21661