Chest
Volume 117, Issue 2, February 2000, Pages 358-364
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Clinical Investigations
Final Results of Phase III Trial in Regionally Advanced Unresectable Non-Small Cell Lung Cancer: Radiation Therapy Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group

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Study objectives

The purpose of this phase III clinical trial was to test whether chemotherapy followed by radiation therapy resulted in superior survival to either hyperfractionated radiation or standard radiation in surgically unresectable non-small cell lung cancer.

Design

Patients were prospectively randomized to 2 months of cisplatin, vinblastine chemotherapy followed by 60 Gy of radiation at 2.0 Gy per fraction or 1.2 Gy per fraction radiation delivered twice daily to a total dose of 69.6 Gy, or 2.0 Gy per fraction of radiation once daily to 60 Gy. Patients were enrolled from January 1989 through January 1992, and followed for a potential minimum period of 5 years.

Setting

This trial was an intergroup National Cancer Institute–funded trial within the Radiation Therapy Oncology Group, the Eastern Cooperative Oncology Group, and the Southwest Oncology Group.

Patients

Patients with surgically unresectable non-small cell lung cancer, clinical stage II, IIIA, and IIIB, were required to have a Karnofsky Performance Status of≥ 70 and a weight loss of < 5% for 3 months before study entry. Four hundred ninety patients were registered on trial, of which 458 patients were eligible.

Conclusion

Overall survival was statistically superior for the patients receiving chemotherapy and radiation vs the other two arms of the study. The twice-daily radiation therapy arm, although better, was not statistically superior in survival for those patients receiving standard radiation. Median survival for standard radiation was 11.4 months; for chemotherapy and irradiation, 13.2 months; and for hyperfractionated irradiation, 12 months. The respective 5-year survivals were 5% for standard radiation therapy, 8% for chemotherapy followed by radiation therapy, and 6% for hyperfractionated irradiation.

Section snippets

Materials and Methods

Methods have been previously described.12 Eligibility included patients who were surgically inoperable with American Joint Committee on Cancer stage II, IIIA, or IIIB non-small cell lung cancer.15 Patients were required to have a KPS≥ 70 and a weight loss of < 5% for 3 months before study entry, to be > 18 years of age, and to have no metastatic disease. Surgical staging was not required. Patients with pleural effusions were excluded from study participation. Pretreatment evaluation required a

Results

Compliance to protocol was acceptable. Approximately 80% of patients received treatment per protocol with minor variation of protocol delivery. Major acceptable variations in treatment were seen in only 5% of patients registered on treatment. One hundred twenty-two of 151 patients had chemotherapy delivered by protocol. Table 3 outlines the delivery of systemic therapy. Toxicity was acceptable. There were six grade 4 or worse acute radiotherapy-related toxic events: four on the

Discussion

The purpose of this trial was to test the hypothesis that either induction chemotherapy followed by irradiation or hyperfractionated irradiation would provide superior survival to standard irradiation in regionally advanced non-small cell lung cancer. This trial represents the largest trial in North America comparing standard irradiation to chemotherapy followed by irradiation in regionally advanced non-small cell lung cancer, and the only phase III trial comparing hyperfractionated irradiation

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    Supported by NIH grants U10 CA21661, CCOP U10 CA37422, and STAT U10 CA32115 to the RTOG (Dr. Sause, Ms. Kolesar, Drs. Taylor, Komaki, Emami, Curran, Byhardt, and Dar); CA 21115 and STAT CA23318 to the ECOG (Drs. Johnson and Turrisi); and U10 CA58861 to the Southwest Oncology Group (Dr. Livingston).

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