A phase I dose escalation study of oxaliplatin plus oral S-1 and pelvic radiation in patients with locally advanced rectal cancer SHOGUN trialReportar como inadecuado




A phase I dose escalation study of oxaliplatin plus oral S-1 and pelvic radiation in patients with locally advanced rectal cancer SHOGUN trial - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Radiation Oncology

, 10:24

First Online: 23 January 2015Received: 02 September 2014Accepted: 12 January 2015DOI: 10.1186-s13014-015-0333-8

Cite this article as: Ishihara, S., Matsusaka, S., Kondo, K. et al. Radiat Oncol 2015 10: 24. doi:10.1186-s13014-015-0333-8

Abstract

BackgroundThe objective of this phase I study was to determine the maximum tolerated dose MTD and recommended dose RD of preoperative chemoradiotherapy CRT with S-1 plus oxaliplatin in patients with locally advanced rectal cancer.

MethodsPatients received radiotherapy in a total dose of 50.4 Gy in 28 fractions. Concurrent chemotherapy consisted of a fixed oral dose of S-1 80 mg-m-day on days 1–5, 8–12, 22–27, and 29–33, plus escalated doses of oxaliplatin as an intravenous infusion on days 1, 8, 22, and 29. Oxaliplatin was initially given in a dose of 40 mg-m-week to three patients. The dose was then increased in a stepwise fashion to 50 mg-m-week and the highest dose level of 60 mg-m-week until the MTD was attained.

ResultsThirteen patients were enrolled, and 12 received CRT. Dose-limiting toxicity DLT occurred in two of six patients persistent grade 2 neutropenia, delaying oxaliplatin treatment by more than 3 days at dose level 3; there were no grade 3 or 4 adverse events defined as DLT. The RD was 60 mg-m-week of oxaliplatin on days 1, 8, 22, and 29. Twelve patients underwent histologically confirmed R0 resections, and two out of six patients 33% given dose level 3 had pathological complete responses.

ConclusionsThe RD for further studies is 80 mg-m of S-1 5 days per week plus 60 mg-m of oxaliplatin on days 1, 8, 22, and 29 and concurrent radiotherapy. Although our results are preliminary, this new regimen for neoadjuvant chemoradiotherapy is considered safe and active.

Trial registrationThis trial was registered with Clinicaltrials.gov identifier: NCT01227239.

KeywordsRectal cancer Chemoradiotherapy Phase I study Oxaliplatin S-1 AbbreviationsTMETotal mesorectal excision

CRMCircumferential resection margin

CRTChemoradiotherapy

pCRpathological complete response

5-FU5-fluorouracil

UFTUracil and tegafur

DLTDose-limiting toxicity

LVLeucovorin

MTDMaximum tolerated dose

RDRecommended dose

CTComputed tomography

MRIMagnetic resonance imaging

3D-CRTThree dimensional conformal radiotherapy

IMRTIntensity modulated radiotherapy

CTVClinical target volume

GTVGross tumor volume

CTCAECommon Terminology Criteria for Adverse Events

TRGTumor Regression Grade

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Autor: Soichiro Ishihara - Satoshi Matsusaka - Keisaku Kondo - Hisanaga Horie - Keisuke Uehara - Masahiko Oguchi - Keiko Murofushi

Fuente: https://link.springer.com/







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