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 journalArticle

10 Citations (Scopus)

Abstract

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
Volume35
Issue number5
DOIs
Publication statusPublished - Oct 2012

Fingerprint

Rectal Neoplasms
oxaliplatin
Radiotherapy
Drug Therapy
Maximum Tolerated Dose
Radiation Oncology
Chemoradiotherapy
raltitrexed
Appointments and Schedules
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Neoadjuvant accelerated concomitant boost radiotherapy and multidrug chemotherapy in locally advanced rectal cancer : A dose-escalation study. / Caravatta, Luciana; Picardi, Vincenzo; Tambaro, Rosa; Padula, Gilbert D A; Macchia, Gabriella; Deodato, Francesco; Massaccesi, Mariangela; Pacelli, Fabio; Berardi, Stefano; Ridolfini, Marco Pericoli; Di Filippo, Loredana; Fabrizio, Giovanni; Ingrosso, Marcello; Cellini, Numa; Valentini, Vincenzo; Morganti, Alessio G.

In: American Journal of Clinical Oncology: Cancer Clinical Trials, Vol. 35, No. 5, 10.2012, p. 424-431.

Research output: Contribution to journalArticle

Caravatta, L, Picardi, V, Tambaro, R, Padula, GDA, Macchia, G, Deodato, F, Massaccesi, M, Pacelli, F, Berardi, S, Ridolfini, MP, Di Filippo, L, Fabrizio, G, Ingrosso, M, Cellini, N, Valentini, V & Morganti, AG 2012, 'Neoadjuvant accelerated concomitant boost radiotherapy and multidrug chemotherapy in locally advanced rectal cancer: A dose-escalation study', American Journal of Clinical Oncology: Cancer Clinical Trials, vol. 35, no. 5, pp. 424-431. https://doi.org/10.1097/COC.0b013e31821a5844
Caravatta, Luciana ; Picardi, Vincenzo ; Tambaro, Rosa ; Padula, Gilbert D A ; Macchia, Gabriella ; Deodato, Francesco ; Massaccesi, Mariangela ; Pacelli, Fabio ; Berardi, Stefano ; Ridolfini, Marco Pericoli ; Di Filippo, Loredana ; Fabrizio, Giovanni ; Ingrosso, Marcello ; Cellini, Numa ; Valentini, Vincenzo ; Morganti, Alessio G. / Neoadjuvant accelerated concomitant boost radiotherapy and multidrug chemotherapy in locally advanced rectal cancer : A dose-escalation study. In: American Journal of Clinical Oncology: Cancer Clinical Trials. 2012 ; Vol. 35, No. 5. pp. 424-431.
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abstract = "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.",
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T1 - Neoadjuvant accelerated concomitant boost radiotherapy and multidrug chemotherapy in locally advanced rectal cancer

T2 - A dose-escalation study

AU - Caravatta, Luciana

AU - Picardi, Vincenzo

AU - Tambaro, Rosa

AU - Padula, Gilbert D A

AU - Macchia, Gabriella

AU - Deodato, Francesco

AU - Massaccesi, Mariangela

AU - Pacelli, Fabio

AU - Berardi, Stefano

AU - Ridolfini, Marco Pericoli

AU - Di Filippo, Loredana

AU - Fabrizio, Giovanni

AU - Ingrosso, Marcello

AU - Cellini, Numa

AU - Valentini, Vincenzo

AU - Morganti, Alessio G.

PY - 2012/10

Y1 - 2012/10

N2 - 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.

AB - 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.

KW - accelerated radiotherapy

KW - neoadjuvant treatment

KW - oxaliplatin

KW - raltitrexed

KW - rectal carcinoma

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