PMID- 23674135
OWN - NLM
STAT- MEDLINE
DCOM- 20140225
LR  - 20201219
IS  - 1097-0142 (Electronic)
IS  - 0008-543X (Linking)
VI  - 119
IP  - 16
DP  - 2013 Aug 15
TI  - Phase 1 study of cetuximab in combination with 5-fluorouracil, cisplatin, and 
      radiotherapy in patients with locally advanced anal canal carcinoma.
PG  - 2973-80
LID - 10.1002/cncr.28045 [doi]
AB  - BACKGROUND: This study sought to determine the feasibility and recommended phase 
      2 dose (RP2D) of the combination of cetuximab with chemoradiotherapy based on 
      5-fluorouracil (5-FU) and cisplatin (CP) in locally advanced anal canal 
      carcinoma. METHODS: Cetuximab was administered on days 1, 8, 15, 29, 36, 43, and 
      50 (400 mg/m(2) initial dose, then 250 mg/m(2) /week) concurrent with total dose 
      radiation of 55 to 59 Gy, both starting on day 1. Escalating doses of 5-FU 
      (96-hour infusion) and CP (2-hour infusion), both on days 1 and 29, were 
      administered according to the following design: starting dose level (0) 
      5-FU/CP = 800/60 mg/m(2) /day and up to dose level (+2) 5-FU/CP = 1000/80 mg/m(2) 
      /day. RESULTS: Dose-limiting toxicity (DLT) events (uncontrolled diarrhea or 
      febrile neutropenia) occurred in 3 of 14 assessable patients receiving escalated 
      dose of 5-FU/CP, with 1 in dose level (0) and 2 in dose level (+2). The RP2D was 
      5-FU/CP = 800/80 mg/m(2) /day. Because of unexpected non-DLT treatment-related 
      grade 3 (G3) adverse events (AEs) such as thrombosis/embolism, syncope, and 
      infection occurring in >/= 20% of patients, a safety expansion cohort with an 
      additional 9 patients was investigated with the RP2D. The most frequent G3/G4 AEs 
      evaluated in 23 patients were radiation dermatitis (12 patients), diarrhea (10 
      patients), thrombosis/embolism (6 patients), and infection (5 patients). The 
      study was closed due to these severe AEs, although no G5 AEs occurred. Twenty of 
      21 patients (95%) achieved pathological complete response at primary tumor. With 
      a median follow-up of 43.4 months, the 3-year locoregional control rate was 
      64.2%. CONCLUSIONS: Cetuximab could not be integrated with 
      chemoradiotherapy-cisplatin-based therapy due to the high toxicity rate. However, 
      efficacy is encouraging and further investigation of an epidermal growth factor 
      receptor-targeted agent (other than cetuximab) concurrent with chemoradiation 
      should be pursued.
CI  - Copyright (c) 2013 American Cancer Society.
FAU - Olivatto, Luis O
AU  - Olivatto LO
AD  - Division of Clinical Oncology, Hospital do Instituto Nacional de Cancer, Rio de 
      Janeiro, Brazil. olivatto@inca.gov.br
FAU - Vieira, Fernando M
AU  - Vieira FM
FAU - Pereira, Bruno V
AU  - Pereira BV
FAU - Victorino, Ana P
AU  - Victorino AP
FAU - Bezerra, Marcos
AU  - Bezerra M
FAU - Araujo, Carlos M
AU  - Araujo CM
FAU - Erlich, Felipe
AU  - Erlich F
FAU - Faroni, Lilian
AU  - Faroni L
FAU - Castro, Leonaldson
AU  - Castro L
FAU - Lusis, Edward C
AU  - Lusis EC
FAU - Marins, Alessandra
AU  - Marins A
FAU - Ferreira, Carlos Gil
AU  - Ferreira CG
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20130514
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - PQX0D8J21J (Cetuximab)
RN  - Q20Q21Q62J (Cisplatin)
RN  - U3P01618RT (Fluorouracil)
RN  - Anal Canal Carcinoma
SB  - IM
CIN - Cancer. 2014 Feb 1;120(3):456. PMID: 24243421
CIN - Cancer. 2014 Feb 1;120(3):454-6. PMID: 24243447
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/administration & dosage/adverse effects
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Anus Neoplasms/*drug therapy/*radiotherapy
MH  - Cetuximab
MH  - Chemoradiotherapy
MH  - Cisplatin/administration & dosage/adverse effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Fluorouracil/administration & dosage/adverse effects
MH  - Humans
MH  - Middle Aged
MH  - Young Adult
OTO - NOTNLM
OT  - 5-fluorouracil
OT  - cetuximab
OT  - chemoradiation
OT  - cisplatin
OT  - locally advanced anal canal carcinoma
EDAT- 2013/05/16 06:00
MHDA- 2014/02/26 06:00
CRDT- 2013/05/16 06:00
PHST- 2012/12/29 00:00 [received]
PHST- 2013/02/15 00:00 [revised]
PHST- 2013/02/19 00:00 [accepted]
PHST- 2013/05/16 06:00 [entrez]
PHST- 2013/05/16 06:00 [pubmed]
PHST- 2014/02/26 06:00 [medline]
AID - 10.1002/cncr.28045 [doi]
PST - ppublish
SO  - Cancer. 2013 Aug 15;119(16):2973-80. doi: 10.1002/cncr.28045. Epub 2013 May 14.