Neoadjuvant accelerated concomitant boost radiotherapy and multidrug chemotherapy in locally advanced rectal cancer: A dose-escalation study

Luciana Caravatta, Vincenzo Picardi, Rosa Tambaro, Gilbert D A Padula, Gabriella Macchia, Francesco Deodato, Mariangela Massaccesi, Fabio Pacelli, Stefano Berardi, Marco Pericoli Ridolfini, Loredana Di Filippo, Giovanni Fabrizio, Marcello Ingrosso, Numa Cellini, Vincenzo Valentini, Alessio G. Morganti

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)424-431
Number of pages8
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Issue number5
Publication statusPublished - Oct 2012


  • accelerated radiotherapy
  • neoadjuvant treatment
  • oxaliplatin
  • raltitrexed
  • rectal carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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