Phase 1 Study of Accelerated Hypofractionated Radiation Therapy With Concurrent Chemotherapy for Stage III Non-Small Cell Lung Cancer: CALGB 31102 (Alliance)

James J. Urbanic, Xiaofei Wang, Jeffrey A. Bogart, Thomas E. Stinchcombe, Lydia Hodgson, Steven E. Schild, Lyudmila Bazhenova, Olwen Hahn, Ravi Salgia, Everett E. Vokes

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Abstract

Purpose: To investigate the safety of accelerated hypofractionated radiation therapy (AHRT) with concurrent chemotherapy (CT) for inoperable stage III non-small cell lung cancer (NSCLC). Patients and Methods: The primary objectives were to define the maximally tolerable course of accelerated radiation therapy and to describe toxicities of therapy. Total radiation therapy remained at 60 Gy. The number of once-daily fractions in each successive cohort was reduced as follows: cohort 1, 60 Gy in 27 fractions; cohort 2, 60 Gy in 24 fractions; cohort 3, 60 Gy in 22 fractions; and cohort 4, 60 Gy in 20 fractions. Concurrent treatment consisted of weekly carboplatin area under the curve (AUC) 2 and paclitaxel 45 mg/m2. Consolidation treatment consisted of carboplatin AUC 6 and paclitaxel 200 mg/m2 every weeks × 2 cycles. Maximum tolerated dose: Of 6 patients/cohort, ≤2 patients experienced grade ≥3 toxicity, and ≤1 patient experienced grade ≥4 toxicity. Results: 22 patients were accrued; of those, 21 patients were evaluable between July 2012 and May 2014. Grade 5 toxicity occurred in 3 patients: 1 patient in cohort 2 (hemoptysis), 2 patients in cohort 3 (hemoptysis, pneumonitis). The maximum tolerated dose (MTD) was defined by cohort 2 (60 Gy in 2.5 Gy/fraction). Time to grade 5 toxicity was 9 months, 6 months, and 9 months after the start of treatment. The median follow-up time was 23.0 months (range, 7.6-30.6 months) in living patients, the median overall survival was 19.3 months (95% confidence interval [CI] 9.3-34.0 months), and the median progression-free survival was 12.2 months (95% CI 6.1-22.5 months). Conclusions: Only modest hypofractionation was achievable as a result of long-term toxicities. Nevertheless, the MTD of 60 Gy given at 2.5 Gy/fraction allows completion of RT in 20% fewer treatments than conventional therapy. Further investigation of AHRT may help to better define the therapeutic index.

Original languageEnglish (US)
JournalInternational Journal of Radiation Oncology Biology Physics
DOIs
StateAccepted/In press - Jan 1 2018

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chemotherapy
Non-Small Cell Lung Carcinoma
lungs
radiation therapy
Radiotherapy
cancer
Drug Therapy
toxicity
Maximum Tolerated Dose
grade
Hemoptysis
Carboplatin
Paclitaxel
dosage
Therapeutics
Area Under Curve
confidence
therapy
Confidence Intervals
intervals

ASJC Scopus subject areas

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

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Phase 1 Study of Accelerated Hypofractionated Radiation Therapy With Concurrent Chemotherapy for Stage III Non-Small Cell Lung Cancer : CALGB 31102 (Alliance). / Urbanic, James J.; Wang, Xiaofei; Bogart, Jeffrey A.; Stinchcombe, Thomas E.; Hodgson, Lydia; Schild, Steven E.; Bazhenova, Lyudmila; Hahn, Olwen; Salgia, Ravi; Vokes, Everett E.

In: International Journal of Radiation Oncology Biology Physics, 01.01.2018.

Research output: Contribution to journalArticle

Urbanic, James J. ; Wang, Xiaofei ; Bogart, Jeffrey A. ; Stinchcombe, Thomas E. ; Hodgson, Lydia ; Schild, Steven E. ; Bazhenova, Lyudmila ; Hahn, Olwen ; Salgia, Ravi ; Vokes, Everett E. / Phase 1 Study of Accelerated Hypofractionated Radiation Therapy With Concurrent Chemotherapy for Stage III Non-Small Cell Lung Cancer : CALGB 31102 (Alliance). In: International Journal of Radiation Oncology Biology Physics. 2018.
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abstract = "Purpose: To investigate the safety of accelerated hypofractionated radiation therapy (AHRT) with concurrent chemotherapy (CT) for inoperable stage III non-small cell lung cancer (NSCLC). Patients and Methods: The primary objectives were to define the maximally tolerable course of accelerated radiation therapy and to describe toxicities of therapy. Total radiation therapy remained at 60 Gy. The number of once-daily fractions in each successive cohort was reduced as follows: cohort 1, 60 Gy in 27 fractions; cohort 2, 60 Gy in 24 fractions; cohort 3, 60 Gy in 22 fractions; and cohort 4, 60 Gy in 20 fractions. Concurrent treatment consisted of weekly carboplatin area under the curve (AUC) 2 and paclitaxel 45 mg/m2. Consolidation treatment consisted of carboplatin AUC 6 and paclitaxel 200 mg/m2 every weeks × 2 cycles. Maximum tolerated dose: Of 6 patients/cohort, ≤2 patients experienced grade ≥3 toxicity, and ≤1 patient experienced grade ≥4 toxicity. Results: 22 patients were accrued; of those, 21 patients were evaluable between July 2012 and May 2014. Grade 5 toxicity occurred in 3 patients: 1 patient in cohort 2 (hemoptysis), 2 patients in cohort 3 (hemoptysis, pneumonitis). The maximum tolerated dose (MTD) was defined by cohort 2 (60 Gy in 2.5 Gy/fraction). Time to grade 5 toxicity was 9 months, 6 months, and 9 months after the start of treatment. The median follow-up time was 23.0 months (range, 7.6-30.6 months) in living patients, the median overall survival was 19.3 months (95{\%} confidence interval [CI] 9.3-34.0 months), and the median progression-free survival was 12.2 months (95{\%} CI 6.1-22.5 months). Conclusions: Only modest hypofractionation was achievable as a result of long-term toxicities. Nevertheless, the MTD of 60 Gy given at 2.5 Gy/fraction allows completion of RT in 20{\%} fewer treatments than conventional therapy. Further investigation of AHRT may help to better define the therapeutic index.",
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T2 - CALGB 31102 (Alliance)

AU - Urbanic, James J.

AU - Wang, Xiaofei

AU - Bogart, Jeffrey A.

AU - Stinchcombe, Thomas E.

AU - Hodgson, Lydia

AU - Schild, Steven E.

AU - Bazhenova, Lyudmila

AU - Hahn, Olwen

AU - Salgia, Ravi

AU - Vokes, Everett E.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Purpose: To investigate the safety of accelerated hypofractionated radiation therapy (AHRT) with concurrent chemotherapy (CT) for inoperable stage III non-small cell lung cancer (NSCLC). Patients and Methods: The primary objectives were to define the maximally tolerable course of accelerated radiation therapy and to describe toxicities of therapy. Total radiation therapy remained at 60 Gy. The number of once-daily fractions in each successive cohort was reduced as follows: cohort 1, 60 Gy in 27 fractions; cohort 2, 60 Gy in 24 fractions; cohort 3, 60 Gy in 22 fractions; and cohort 4, 60 Gy in 20 fractions. Concurrent treatment consisted of weekly carboplatin area under the curve (AUC) 2 and paclitaxel 45 mg/m2. Consolidation treatment consisted of carboplatin AUC 6 and paclitaxel 200 mg/m2 every weeks × 2 cycles. Maximum tolerated dose: Of 6 patients/cohort, ≤2 patients experienced grade ≥3 toxicity, and ≤1 patient experienced grade ≥4 toxicity. Results: 22 patients were accrued; of those, 21 patients were evaluable between July 2012 and May 2014. Grade 5 toxicity occurred in 3 patients: 1 patient in cohort 2 (hemoptysis), 2 patients in cohort 3 (hemoptysis, pneumonitis). The maximum tolerated dose (MTD) was defined by cohort 2 (60 Gy in 2.5 Gy/fraction). Time to grade 5 toxicity was 9 months, 6 months, and 9 months after the start of treatment. The median follow-up time was 23.0 months (range, 7.6-30.6 months) in living patients, the median overall survival was 19.3 months (95% confidence interval [CI] 9.3-34.0 months), and the median progression-free survival was 12.2 months (95% CI 6.1-22.5 months). Conclusions: Only modest hypofractionation was achievable as a result of long-term toxicities. Nevertheless, the MTD of 60 Gy given at 2.5 Gy/fraction allows completion of RT in 20% fewer treatments than conventional therapy. Further investigation of AHRT may help to better define the therapeutic index.

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