A Phase I/II Radiation Dose Escalation Study With Concurrent Chemotherapy for Patients With Inoperable Stages I to III Non-Small-Cell Lung Cancer

Phase I Results of RTOG 0117

Jeffrey D. Bradley, Jennifer Moughan, Mary V. Graham, Roger Byhardt, Ramaswamy Govindan, Jack Fowler, James A. Purdy, Jeff M. Michalski, Elizabeth Gore, Hak Choy

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Purpose: In preparation for a Phase III comparison of high-dose versus standard-dose radiation therapy, this Phase I/II study was initiated to establish the maximum tolerated dose of radiation therapy in the setting of concurrent chemotherapy, using three-dimensional conformal radiation therapy for non-small-cell lung cancer. Methods and Materials: Eligibility included patients with histologically proven, unresectable Stages I to III non-small-cell lung cancer. Concurrent chemotherapy consisted of paclitaxel, 50 mg/m2, and carboplatin, AUC of 2, given weekly. The radiation dose was to be sequentially intensified by increasing the daily fraction size, starting from 75.25 Gy/35 fractions. Results: The Phase I portion of this study accrued 17 patients from 10 institutions and was closed in January 2004. After the initial 8 patients were accrued to cohort 1, the trial closed temporarily on September 26, 2002, due to reported toxicity. Two acute treatment-related dose-limiting toxicities (DLTs) were reported at the time: a case of grade 5 and grade 3 radiation pneumonitis. The protocol, therefore, was revised to de-escalate the radiation therapy dose (74 Gy/37 fractions). Patients in cohort 1 continued to develop toxicity, with 6/8 (75%) patients eventually developing grade ≥3 events. Cohort 2 accrued 9 patients. There was one DLT, a grade 3 esophagitis, in cohort 2 in the first 5 patients (1/5 patients) and no DLTs for the next 2 patients (0/2 patients). Conclusions: The maximum tolerated dose was determined to be 74 Gy/37 fractions (2.0 Gy per fraction) using three-dimensional conformal radiation therapy with concurrent paclitaxel and carboplatin therapy. This dose level in the Phase II portion has been well tolerated, with low rates of acute and late lung toxicities.

Original languageEnglish (US)
Pages (from-to)367-372
Number of pages6
JournalInternational Journal of Radiation Oncology Biology Physics
Volume77
Issue number2
DOIs
StatePublished - Jun 1 2010

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chemotherapy
Non-Small Cell Lung Carcinoma
lungs
Cohort Studies
cancer
Radiation
Drug Therapy
dosage
toxicity
radiation
radiation therapy
Radiotherapy
grade
Maximum Tolerated Dose
Carboplatin
Paclitaxel
Radiation Pneumonitis
Esophagitis
Area Under Curve
therapy

Keywords

  • Concurrent chemoradiation therapy
  • Dose escalation
  • Lung cancer
  • RTOG

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation
  • Cancer Research

Cite this

A Phase I/II Radiation Dose Escalation Study With Concurrent Chemotherapy for Patients With Inoperable Stages I to III Non-Small-Cell Lung Cancer : Phase I Results of RTOG 0117. / Bradley, Jeffrey D.; Moughan, Jennifer; Graham, Mary V.; Byhardt, Roger; Govindan, Ramaswamy; Fowler, Jack; Purdy, James A.; Michalski, Jeff M.; Gore, Elizabeth; Choy, Hak.

In: International Journal of Radiation Oncology Biology Physics, Vol. 77, No. 2, 01.06.2010, p. 367-372.

Research output: Contribution to journalArticle

Bradley, Jeffrey D. ; Moughan, Jennifer ; Graham, Mary V. ; Byhardt, Roger ; Govindan, Ramaswamy ; Fowler, Jack ; Purdy, James A. ; Michalski, Jeff M. ; Gore, Elizabeth ; Choy, Hak. / A Phase I/II Radiation Dose Escalation Study With Concurrent Chemotherapy for Patients With Inoperable Stages I to III Non-Small-Cell Lung Cancer : Phase I Results of RTOG 0117. In: International Journal of Radiation Oncology Biology Physics. 2010 ; Vol. 77, No. 2. pp. 367-372.
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abstract = "Purpose: In preparation for a Phase III comparison of high-dose versus standard-dose radiation therapy, this Phase I/II study was initiated to establish the maximum tolerated dose of radiation therapy in the setting of concurrent chemotherapy, using three-dimensional conformal radiation therapy for non-small-cell lung cancer. Methods and Materials: Eligibility included patients with histologically proven, unresectable Stages I to III non-small-cell lung cancer. Concurrent chemotherapy consisted of paclitaxel, 50 mg/m2, and carboplatin, AUC of 2, given weekly. The radiation dose was to be sequentially intensified by increasing the daily fraction size, starting from 75.25 Gy/35 fractions. Results: The Phase I portion of this study accrued 17 patients from 10 institutions and was closed in January 2004. After the initial 8 patients were accrued to cohort 1, the trial closed temporarily on September 26, 2002, due to reported toxicity. Two acute treatment-related dose-limiting toxicities (DLTs) were reported at the time: a case of grade 5 and grade 3 radiation pneumonitis. The protocol, therefore, was revised to de-escalate the radiation therapy dose (74 Gy/37 fractions). Patients in cohort 1 continued to develop toxicity, with 6/8 (75{\%}) patients eventually developing grade ≥3 events. Cohort 2 accrued 9 patients. There was one DLT, a grade 3 esophagitis, in cohort 2 in the first 5 patients (1/5 patients) and no DLTs for the next 2 patients (0/2 patients). Conclusions: The maximum tolerated dose was determined to be 74 Gy/37 fractions (2.0 Gy per fraction) using three-dimensional conformal radiation therapy with concurrent paclitaxel and carboplatin therapy. This dose level in the Phase II portion has been well tolerated, with low rates of acute and late lung toxicities.",
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AU - Moughan, Jennifer

AU - Graham, Mary V.

AU - Byhardt, Roger

AU - Govindan, Ramaswamy

AU - Fowler, Jack

AU - Purdy, James A.

AU - Michalski, Jeff M.

AU - Gore, Elizabeth

AU - Choy, Hak

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