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

Alternate Title

Radiation Therapy Plus Chemotherapy in Treating Patients With Non-small Cell Lung Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	18 and over	NCI	RTOG-9410 RTOG-94-10

Objectives

I.  Compare the survival rate of patients with locally advanced, unresectable 
non-small cell lung cancer randomized to concomitant vinblastine/cisplatin 
(VBL/CDDP) and thoracic radiotherapy versus sequential VBL/CDDP and once-daily 
thoracic radiotherapy.

II.  Compare the survival rate of such patients randomized to 2 courses of 
concomitant etoposide/cisplatin and hyperfractionated thoracic radiotherapy 
versus sequential VBL/CDDP and once-daily thoracic radiotherapy.

III.  Assess the frequency of treatment-related esophageal and hematologic 
toxicity/morbidity in patients on concomitant versus sequential chemoradiation 
treatment arms.

Entry Criteria

Disease Characteristics:

Locoregionally advanced, inoperable, non-small cell lung cancer with no
evidence of distant metastases, i.e.:
  Stage II/IIIA medically inoperable disease

  Stage IIIA/IIIB unresectable disease

No pleural effusion
  Appearance after an invasive thoracic procedure allowed

No more than 5% weight loss within 3 months prior to diagnosis

Confirmed N2 disease should first be evaluated for protocol RTOG-9309

Prior/Concurrent Therapy:

Biologic therapy:
  Not specified

Chemotherapy:
  No prior chemotherapy

Endocrine therapy:
  Not specified

Radiotherapy:
  No prior thoracic or neck radiotherapy

Surgery:
  No prior complete or nearly complete tumor resection

Patient Characteristics:

Age:
  At least 18

Performance status:
  Karnofsky 70%-100%

Hematopoietic:
  AGC at least 2,000
  Platelets at least 100,000
  Hemoglobin at least 8.0 g/dL

Hepatic:
  (unless abnormality caused by benign disease)
  Bilirubin no more than 1.5 times normal
  AST no more than 1.5 times normal

Renal:
  Creatinine no more than 1.5 mg/dL

Cardiovascular:
  No myocardial infarction within the past 6 months
  No angina
  No congestive heart failure
  No uncontrolled arrhythmia

Other:
  No synchronous or prior invasive malignancy within 3 years except
     nonmelanomatous skin cancer
  No pregnant women
  Effective contraception required of fertile patients

Expected Enrollment

A total of 597 patients will be entered over 3.1-4.2 years.  If fewer than 6 
patients/month are accrued, the feasibility of the study will be re-evaluated.

Outline

Randomized study.  The following acronyms are used:
  CDDP     Cisplatin, NSC-119875
  VBL      Vinblastine, NSC-49842
  VP-16    Etoposide, NSC-141540

Arm I:  2-Drug Combination Chemotherapy Followed by Radiotherapy.  CDDP/VBL; 
followed by thoracic irradiation using photons of at least 6 MV (electrons may 
be used to boost the supraclavicular lymph nodes).

Arm II:  Radiotherapy plus 2-Drug Combination Chemotherapy.  Thoracic 
irradiation using equipment as in Arm I; plus CDDP/VBL.

Arm III:  Hyperfractionated Radiotherapy plus 2-Drug Combination Chemotherapy. 
 Thoracic irradiation using equipment as in Arm I; plus CDDP/VP-16.

Curran WJ, Scott CB, Langer CJ, et al.: Long-term benefit is observed in a phase III comparison of sequential vs concurrent chemo-radiation for patients with unresected stage III nsclc: RTOG 9410. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-2499, 2003.

Langer CJ, Hsu C, Curran WJ, et al.: Elderly patients (pts) with locally advanced non-small cell lung cancer (LA-NSCLC) benefit from combined modality therapy: secondary analysis of Radiation Therapy Oncology Group (RTOG) 94-10. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-1193, 2002.

Langer CJ, Hsu C, Curran W, et al.: Do elderly patients (pts) with locally advanced non-small cell lung cancer (NSCLC) benefit from combined modality therapy? A secondary analysis of RTOG 94-10. [Abstract] Int J Radiat Oncol Biol Phys 51(3 suppl 1): A-36, 20-21, 2001.

Movsas B, Scott C, Curran W, et al.: A quality-adjusted time without symptons or toxicity (QTWiST) analysis of Radiation Therapy Oncology Group (RTOG) 94-10. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-1247, 313a, 2001.

Curran WJ, Scott C, Langer C, et al.: Phase III comparison of sequential vs concurrent chemoradiation for patients with unresected stage III non-small cell lung cancer (NSCLC): initial report of Radiation Therapy Oncology Group (RTOG) 9410. [Abstract] Proceedings of the American Society of Clinical Oncology 19: A1891, 2000.

Komaki R, Seiferheld W, Curran W, et al.: Sequential vs. concurrent chemotherapy and radiation therapy for inoperable non-small cell lung cancer (NSCLC): analysis of failures in a phase III study (RTOG 9410). [Abstract] Int J Radiat Oncol Biol Phys 48 (3 suppl): A-5, 113, 2000.

Konski AA, Bhargavan M, Owen J, et al.: “Less is not always more”: an economic analysis of Radiation Therapy Oncology Group 94–10. [Abstract] Int J Radiat Oncol Biol Phys 69 (3 Suppl): A-1080, S182, 2007.

Choy H, Swann S, Nabid A, et al.: Comparison of 5-year survival between RTOG-94-10 and a phase 2 study of induction chemotherapy followed by efaproxiral + radiotherapy in patients with locally advanced NSCLC. [Abstract] Int J Radiat Oncol Biol Phys 66 (3 Suppl 1): A-49, S28-9, 2006.

Bradley J: A review of radiation dose escalation trials for non-small cell lung cancer within the Radiation Therapy Oncology Group. Semin Oncol 32 (2 Suppl 3): S111-3, 2005.[PUBMED Abstract]

Langer CJ, Swann S, Curran W, et al.: Reassessing prognostic factors in the era of combined modality therapy for locally advanced NSCLC: a retrospective analysis of RTOG 9410 and 9801. [Abstract] Int J Radiat Oncol Biol Phys 63 (2 Suppl 1): A-65, S39, 2005.

Machtay M, Hsu C, Komaki R, et al.: Effect of overall treatment time on outcomes after concurrent chemoradiation for locally advanced non-small-cell lung carcinoma: analysis of the Radiation Therapy Oncology Group (RTOG) experience. Int J Radiat Oncol Biol Phys 63 (3): 667-71, 2005.[PUBMED Abstract]

Machtay M, Swann S, Komaki R, et al.: Overall treatment time during concurrent chemoradiotherapy and outcomes: an RTOG secondary analysis. [Abstract] Lung Cancer 50 (Suppl 2): A-O-042, S17, 2005.

Machtay M, Swann S, Komaki R, et al.: What is the meaning of local-regional control after chemoradiation for locally advanced NSCLC? An RTOG analysis. [Abstract] Lung Cancer 50 (Suppl 2): A-O-041, S17, 2005.

Swann RS, Machtay M, Komaki R, et al.: Impact of overall treatment time during concurrent chemoradiotherapy for locally advanced NSCLC: an RTOG secondary analysis. [Abstract] J Clin Oncol 23 (Suppl 16): A-7061, 635s, 2005.

Werner-Wasik M, Scott C, Curran WJ, et al.: Correlation between acute esophagitis and late pneumonitis in patients (pts) with locally advanced non-small cell lung cancer (LA-NSCLC) receiving concurrent thoracic radiotherapy (RT) and chemotherapy: a multivariate analysis of the Radiation Therapy Oncology Group (RTOG) database. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-1192, 2002.

Sause W, Scott C, Byhardt R, et al.: Combined chemotheray radiation therapy treatment in unresected non-small cell lung cancer: Radiation Therapy Oncology Group (RTOG) experience. Lung Cancer 29(suppl 2): 2000.

Trial Contact Information

Trial Lead Organizations

Radiation Therapy Oncology Group

Walter Curran, MD, Protocol chair(Contact information may not be current)		Ph: 215-955-6700; 800-533-3669 Email: walter.curran@jeffersonhospital.org