OBJECTIVES: To determine the maximal and safely dose of preoperative radiotherapy and concurrently intensified chemotherapy regimen (raltitrexed plus oxaliplatin) in locally advanced rectal cancer patients. METHODS: Patients with cT3-T4 and/or cN≥1 or locally recurrent rectal cancer were sequentially assigned to 4 treatment schedules of chemoradiation: standard radiotherapy (50.4 Gy/5.5 wk) plus raltitrexed (cohort A), accelerated radiotherapy (55 Gy/5 wk) plus raltitrexed (cohort B), standard radiotherapy plus raltitrexed and oxaliplatin (cohort C), accelerated radiotherapy plus raltitrexed and oxaliplatin (cohort D). Patients were treated in cohorts of 6 to 12 per group. The maximal tolerated dose was exceeded if more than one-third of patients in a given cohort experienced dose-limiting toxicity (DLT). DLT was defined as any grade ≥3 toxicity according to the Radiation Therapy Oncology Group criteria. RESULTS: Forty-six consecutive patients were enrolled. In cohort A, 6 patients received the planned treatment with no DLT. In cohort B, 1 of 8 patients experienced a DLT. In cohort C, a DLT occurred in 2 of 6 patients and therefore, a cohort expansion was required. Three of 16 patients treated at this dose level experienced a DLT. In addition, cohort D was expanded and DLT was found in 4 of 16 patients. Therefore, the maximal tolerated dose was not exceeded at any treatment level. CONCLUSIONS: An intensified regimen of chemoradiotherapy delivering raltitrexed and oxaliplatin concurrently with concomitant boost radiotherapy (55 Gy/5 wk) can be safely administered in patients with locally advanced rectal cancer. On the basis of these results, this intensified regimen could be tested in a phase II study.
OBJECTIVES: To determine the maximal and safely dose of preoperative radiotherapy and concurrently intensified chemotherapy regimen (raltitrexed plus oxaliplatin) in locally advanced rectal cancerpatients. METHODS:Patients with cT3-T4 and/or cN≥1 or locally recurrent rectal cancer were sequentially assigned to 4 treatment schedules of chemoradiation: standard radiotherapy (50.4 Gy/5.5 wk) plus raltitrexed (cohort A), accelerated radiotherapy (55 Gy/5 wk) plus raltitrexed (cohort B), standard radiotherapy plus raltitrexed and oxaliplatin (cohort C), accelerated radiotherapy plus raltitrexed and oxaliplatin (cohort D). Patients were treated in cohorts of 6 to 12 per group. The maximal tolerated dose was exceeded if more than one-third of patients in a given cohort experienced dose-limiting toxicity (DLT). DLT was defined as any grade ≥3 toxicity according to the Radiation Therapy Oncology Group criteria. RESULTS: Forty-six consecutive patients were enrolled. In cohort A, 6 patients received the planned treatment with no DLT. In cohort B, 1 of 8 patients experienced a DLT. In cohort C, a DLT occurred in 2 of 6 patients and therefore, a cohort expansion was required. Three of 16 patients treated at this dose level experienced a DLT. In addition, cohort D was expanded and DLT was found in 4 of 16 patients. Therefore, the maximal tolerated dose was not exceeded at any treatment level. CONCLUSIONS: An intensified regimen of chemoradiotherapy delivering raltitrexed and oxaliplatin concurrently with concomitant boost radiotherapy (55 Gy/5 wk) can be safely administered in patients with locally advanced rectal cancer. On the basis of these results, this intensified regimen could be tested in a phase II study.
Authors: Monica DI Tommaso; Consuelo Rosa; Luciana Caravatta; Antonietta Augurio; Valentina Borzillo; Sara DI Santo; Francesca Perrotti; Maria Taraborrelli; Roberta Cianci; Paolo Innocenti; Pierluigi DI Sebastiano; Antonella Colasante; Domenico Angelucci; Massimo Basti; Giulia Sindici; Lorenzo Mazzola; Giuseppe Pizzicannella; Nicola DI Bartolomeo; Michele Marchioni; Marta DI Nicola; Domenico Genovesi Journal: In Vivo Date: 2020 May-Jun Impact factor: 2.155
Authors: Stanley K T Yu; Aneel Bhangu; Diana M Tait; Paris Tekkis; Andrew Wotherspoon; Gina Brown Journal: Cancer Med Date: 2013-12-16 Impact factor: 4.452
Authors: E González-Flores; F Losa; C Pericay; E Polo; S Roselló; M J Safont; R Vera; J Aparicio; M T Cano; C Fernández-Martos Journal: Clin Transl Oncol Date: 2016-11-30 Impact factor: 3.405
Authors: Jillian R Gunther; Awalpreet S Chadha; Ui Sup Shin; In Ja Park; Kiran V Kattepogu; Jonathan D Grant; David C Weksberg; Cathy Eng; Scott E Kopetz; Prajnan Das; Marc E Delclos; Harmeet Kaur; Dipen M Maru; John M Skibber; Miguel A Rodriguez-Bigas; Y Nancy You; Sunil Krishnan; George J Chang Journal: Adv Radiat Oncol Date: 2017-04-12