Concomitant boost dose escalation plus large-field preoperative chemoradiation in locally advanced carcinoma of the uterine cervix: Results of a phase I study (LARA-CC-1)

Objective. To determine the recommended preoperative dose of large-field chemoradiation along with concomitant boost dose escalation on the tumor in locally advanced cervical carcinoma (LACC). Patients and methods. A radiation dose of 40 Gy over four weeks, 2 Gy per fraction, was delivered to the tumor and the lymphatic drainage (planning target volume, PTV2), which encompassed a volume larger than standard (upper field border: L3 vertebra), concurrently with chemotherapy (cisplatin and 5-fluorouracil). Radiation dose was escalated to the macroscopic tumor only (PTV1) with a concomitant boost strategy. Three close levels were planned: levels 1 (no PTV1 boost), 2 (45/2.25 Gy) and 3 (50/2.5 Gy). Patients were treated in cohorts of six to twelve per group using a standard phase I study design. The recommended dose was exceeded if >2 of 6 patients in a cohort experienced dose-limiting toxicity (DLT). Results. 32 patients (median age: 50 years: FIGO stage 182: 4, IIA: 3, IIB: 21, III-IVA: 4) were enrolled. Median follow-up was 18 months (3-49 months). The most common grade 3/4 toxicity was gastrointestinal (diarrhea). Since three DLTs (grade 3 diarrhea, n = 2; grade 3 proctitis, n = 1), were observed in 4 patients at level 3, the trial was closed and level 2 was judged as the recommended dose. Conclusion. Based on the data from this phase I study, 45 Gy/2.25 Gy to macroscopic tumor and 40 Gy/2 Gy to lymphatic drainage may be considered the recommended doses. (C) 2010 Elsevier Inc. All rights reserved.