International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationA 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
Introduction
The standard dose, volume, and beam arrangements for the treatment of non-small-cell lung cancer (NSCLC) were established by Radiation Therapy Oncology Group (RTOG) dose escalation trial 7301 (1). This trial included patients with inoperable stage III disease, who received radiation therapy only. Since current radiation parameters were established by that trial, a number of changes in treatment have occurred, including the addition of concurrent chemotherapy and the application of three-dimensional conformal radiation therapy (3DCRT). RTOG 9311 was a subsequent protocol that escalated the radiation dose with 3DCRT without concurrent chemotherapy (2). The total dose was based on the percent volume of normal lung exceeding 20 Gy (V20). RTOG 9311 established that the maximum tolerated doses (MTD) of radiation alone were 83.8 Gy for patients with V20 values of <25% and 77.4 Gy for V20 values between 25 and 36%. Near the close of this study, results of randomized trials were reported that demonstrated a survival advantage in favor of concurrent chemotherapy compared to radiation alone or to sequential chemotherapy followed by radiation therapy 3, 4, 5, 6, 7. Therefore, the objectives for RTOG 0117 were to establish the MTD of radiation therapy in the setting of concurrent paclitaxel and carboplatin therapy, using 3DCRT for patients with inoperable NSCLC (Phase I), and to estimate the percentage of patients who survive at least 12 months with this regimen (Phase II). This report addresses the Phase I results of this trial.
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Methods and Materials
Between July 13, 2001, and January 13, 2004, 17 patients were enrolled in the Phase I portion of the study. Eligible patients had histologically proven stage I to IIIB NSCLC, Zubrod performance status levels of 0 to 1, a weight loss of ≤5% within the previous 6 months, a forced expiratory volume at 1 second of ≤1 liter, and atelectasis involvement, if present, in less than one lung. Based on conformal treatment planning, the volume of the lung at or exceeding 20 Gy (V20) had to be ≤30% and a
Results
Accrual for the Phase I portion was from nine RTOG institutions (15 of 17 patients) and one RTOG community clinical oncology program.
The Phase I portion of this study had 8 eligible and evaluable patients in cohort 1 (receiving 75.25 Gy/35 fractions) and 9 patients in cohort 2 (receiving 74 Gy/37 fractions). The distributions of pretreatment characteristics for each of the Phase I arms are given in Table 2. Patients ranged in age from 48 to 81 years old. Cohort 1 had 4 (50%) patients with a
Discussion
The currently accepted “standard of care” for patients with locally advanced NSCLC is concurrent radiation plus chemotherapy. Recently, most research has focused on which chemotherapy drugs to use and how to integrate them with radiation therapy. Moreover, little attention has been given to optimizing radiation therapy. In particular, the nationally accepted standard radiation prescription dose has remained at the same level (60–63 Gy) for more than 30 years (1). Doses in this range provide
Conclusions
Based on the results of RTOG 0117, NCCTG N0028, and CALGB 30105, 74 Gy has been established as the MTD of radiation therapy when given with weekly concurrent carboplatin and paclitaxel chemotherapy. These three cooperative groups have initiated a Phase III intergroup trial (RTOG 0617/ NCCTG N0628/ CALGB 30609) testing 74 Gy versus 60 Gy with concurrent chemotherapy for patients with inoperable stage III NSCLC.
References (13)
- et al.
Toxicity and outcome results of RTOG 9311: A phase I-II dose-escalation study using three-dimensional conformal radiotherapy in patients with inoperable non-small-cell lung carcinoma
Int J Radiat Oncol Biol Phys
(2005) - et al.
Concurrent versus sequential chemoradiotherapy with cisplatin and vinorelbine in locally advanced non-small cell lung cancer: a randomized study
Lung Cancer
(2004) - et al.
Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC)
Int J Radiat Oncol Biol Phys
(1995) - et al.
Hypofractionated stereotactic radiotherapy (HypoFXSRT) for stage I non-small-cell lung cancer: Updated results of 257 patients in a Japanese multi-institutional study
J Thorac Oncol
(2007) - et al.
Results of a Phase I trial of concurrent chemotherapy and escalating doses of radiation for unresectable non-small-cell lung cancer
Int J Radiat Oncol Biol Phys
(2005) - et al.
A prospective randomized study of various irradiation doses and fractionation schedules in the treatment of inoperable non-oat-cell carcinoma of the lung. Preliminary report by the Radiation Therapy Oncology Group
Cancer
(1980)
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This work was supported by National Cancer Institute grants RTOG U10 CA21661, CCOP U10 CA37422, Stat U10 CA32115, and ITC U24 CA081647.
Conflict of interest: none.