IDEAL-CRT: A Phase 1/2 Trial of Isotoxic Dose-Escalated Radiation Therapy and Concurrent Chemotherapy in Patients With Stage II/III Non-Small Cell Lung Cancer

Abstract

PurposeTo report toxicity and early survival data for IDEAL-CRT, a trial of dose-escalated concurrent chemoradiotherapy (CRT) for non-small cell lung cancer.Patients and MethodsPatients received tumor doses of 63 to 73 Gy in 30 once-daily fractions over 6 weeks with 2 concurrent cycles of cisplatin and vinorelbine. They were assigned to 1 of 2 groups according to esophageal dose. In group 1, tumor doses were determined by an experimental constraint on maximum esophageal dose, which was escalated following a 6 + 6 design from 65 Gy through 68 Gy to 71 Gy, allowing an esophageal maximum tolerated dose to be determined from early and late toxicities. Tumor doses for group 2 patients were determined by other tissue constraints, often lung. Overall survival, progression-free survival, tumor response, and toxicity were evaluated for both groups combined.ResultsEight centers recruited 84 patients: 13, 12, and 10, respectively, in the 65-Gy, 68-Gy, and 71-Gy cohorts of group 1; and 49 in group 2. The mean prescribed tumor dose was 67.7 Gy. Five grade 3 esophagitis and 3 grade 3 pneumonitis events were observed across both groups. After 1 fatal esophageal perforation in the 71-Gy cohort, 68 Gy was declared the esophageal maximum tolerated dose. With a median follow-up of 35 months, median overall survival was 36.9 months, and overall survival and progression-free survival were 87.8% and 72.0%, respectively, at 1 year and 68.0% and 48.5% at 2 years.ConclusionsIDEAL-CRT achieved significant treatment intensification with acceptable toxicity and promising survival. The isotoxic design allowed the esophageal maximum tolerated dose to be identified from relatively few patients.

The Challenges Faced in Developing Novel Drug Radiation Combinations in Non-small Cell Lung Cancer

“…In this study the median survival was 24.3 months in the concurrent setting compared to 18.4 months in the sequential arm and there has been much interest and progress in combining other modified fractionation regimens with cytotoxic chemotherapy [18,19] Potential therapeutic targets to enhance radiotherapy effectiveness.…”

An overview on personalisation of radiotherapy prescriptions in locally advanced non-small cell lung cancer: Are we there yet?

“…As a result, the findings were evaluated in a qualitative manner. 19 relevant publications were identified (Figure1) [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32].…”

“…Following the establishment of feasibility, prospective clinical trials were implemented to evaluate the use of personalised prescriptions in a patient population. Five prospective clinical trials [19][20][21][22][23] were identified that utilised isotoxic treatment planning techniques to individually prescribe RT for LA-NSCLC. Findings from these five trials are summarised in Table 2.…”

“…There was sizeable heterogeneity between these trials. The study by van Baardwijk et al (2010) and Wanet et al were prospective single arm studies [19,23] whilst the remaining three studies were Phase I and Phase II clinical trials [20][21][22]. The patient population inclusion criteria varied.…”

“…The patient population inclusion criteria varied. Two studies [19,21] included only patients receiving RT, whereas patients receiving concurrent CRT were included in the remaining three studies [20,22,23]. Disease stages I-IV were included over the five studies.…”