A phase II trial of erlotinib monotherapy in advanced pancreatic cancer as a first- or second-line agent

Christos Fountzilas, Ravi Chhatrala, Nikhil Khushalani, Wei Tan, Charles LeVea, Alan Hutson, Chris Tucker, Wen Wee Ma, Graham Warren, Patrick Boland, Renuka Iyer

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Introduction: Pancreatic adenocarcinoma carries a grim prognosis. In 2007, gemcitabine with erlotinib emerged as an appropriate treatment option for patients with advanced inoperable or metastatic disease (APC). In this phase II trial we sought to evaluate the efficacy of erlotinib monotherapy in patients with APC who had disease refractory to or ineligibility for gemcitabine-based therapy. Methods: Eligible patients who had received 0 or 1 non-EGFR inhibitor containing gemcitabine-based chemotherapy for APC were recruited prospectively and treated with erlotinib 150 mg orally daily until unacceptable toxicity or disease progression. Primary endpoint was progression-free survival (PFS). Correlations of clinical response with smoking, rash, steady-state concentration of erlotinib and its metabolite (OSI-420) as well as the nicotine metabolite cotinine were performed. Results: The trial was terminated early for futility. Eighteen of the 34 planned subjects were recruited. Median PFS and OS were 42 and 95 days, respectively. Best response was stable disease (21%). There was a trend for improved PFS and OS in never smokers compared to current and past smokers (128.5, 39, 42 days and 173, 100, 88 days, respectively). Past/current smokers had lower steady-state concentrations of erlotinib and OSI-420 compared to never smokers. There was evidence of recent smoking exposure in 30% of patients self-identified as past smokers. Rash was infrequent, with no cases of grade III/IV rash and it was not related to treatment outcomes. Conclusions: Overall, erlotinib monotherapy failed to improve outcomes compared to historical controls in patients with APC after 0–1 prior systemic therapies. There was a trend for improved PFS and OS in never smokers.

Original languageEnglish (US)
Pages (from-to)497-505
Number of pages9
JournalCancer Chemotherapy and Pharmacology
Volume80
Issue number3
DOIs
StatePublished - Sep 1 2017

Fingerprint

gemcitabine
Pancreatic Neoplasms
Disease-Free Survival
Exanthema
Metabolites
Smoking
Medical Futility
Cotinine
Chemotherapy
Nicotine
Refractory materials
Toxicity
Disease Progression
Erlotinib Hydrochloride
Adenocarcinoma
Therapeutics
Drug Therapy

Keywords

  • Cotinine
  • Erlotinib
  • Pancreatic cancer
  • Smoking

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Cite this

A phase II trial of erlotinib monotherapy in advanced pancreatic cancer as a first- or second-line agent. / Fountzilas, Christos; Chhatrala, Ravi; Khushalani, Nikhil; Tan, Wei; LeVea, Charles; Hutson, Alan; Tucker, Chris; Ma, Wen Wee; Warren, Graham; Boland, Patrick; Iyer, Renuka.

In: Cancer Chemotherapy and Pharmacology, Vol. 80, No. 3, 01.09.2017, p. 497-505.

Research output: Contribution to journalArticle

Fountzilas, C, Chhatrala, R, Khushalani, N, Tan, W, LeVea, C, Hutson, A, Tucker, C, Ma, WW, Warren, G, Boland, P & Iyer, R 2017, 'A phase II trial of erlotinib monotherapy in advanced pancreatic cancer as a first- or second-line agent', Cancer Chemotherapy and Pharmacology, vol. 80, no. 3, pp. 497-505. https://doi.org/10.1007/s00280-017-3375-9
Fountzilas, Christos ; Chhatrala, Ravi ; Khushalani, Nikhil ; Tan, Wei ; LeVea, Charles ; Hutson, Alan ; Tucker, Chris ; Ma, Wen Wee ; Warren, Graham ; Boland, Patrick ; Iyer, Renuka. / A phase II trial of erlotinib monotherapy in advanced pancreatic cancer as a first- or second-line agent. In: Cancer Chemotherapy and Pharmacology. 2017 ; Vol. 80, No. 3. pp. 497-505.
@article{af5b663cd2ff4761bae2bb575ff58a46,
title = "A phase II trial of erlotinib monotherapy in advanced pancreatic cancer as a first- or second-line agent",
abstract = "Introduction: Pancreatic adenocarcinoma carries a grim prognosis. In 2007, gemcitabine with erlotinib emerged as an appropriate treatment option for patients with advanced inoperable or metastatic disease (APC). In this phase II trial we sought to evaluate the efficacy of erlotinib monotherapy in patients with APC who had disease refractory to or ineligibility for gemcitabine-based therapy. Methods: Eligible patients who had received 0 or 1 non-EGFR inhibitor containing gemcitabine-based chemotherapy for APC were recruited prospectively and treated with erlotinib 150 mg orally daily until unacceptable toxicity or disease progression. Primary endpoint was progression-free survival (PFS). Correlations of clinical response with smoking, rash, steady-state concentration of erlotinib and its metabolite (OSI-420) as well as the nicotine metabolite cotinine were performed. Results: The trial was terminated early for futility. Eighteen of the 34 planned subjects were recruited. Median PFS and OS were 42 and 95 days, respectively. Best response was stable disease (21{\%}). There was a trend for improved PFS and OS in never smokers compared to current and past smokers (128.5, 39, 42 days and 173, 100, 88 days, respectively). Past/current smokers had lower steady-state concentrations of erlotinib and OSI-420 compared to never smokers. There was evidence of recent smoking exposure in 30{\%} of patients self-identified as past smokers. Rash was infrequent, with no cases of grade III/IV rash and it was not related to treatment outcomes. Conclusions: Overall, erlotinib monotherapy failed to improve outcomes compared to historical controls in patients with APC after 0–1 prior systemic therapies. There was a trend for improved PFS and OS in never smokers.",
keywords = "Cotinine, Erlotinib, Pancreatic cancer, Smoking",
author = "Christos Fountzilas and Ravi Chhatrala and Nikhil Khushalani and Wei Tan and Charles LeVea and Alan Hutson and Chris Tucker and Ma, {Wen Wee} and Graham Warren and Patrick Boland and Renuka Iyer",
year = "2017",
month = "9",
day = "1",
doi = "10.1007/s00280-017-3375-9",
language = "English (US)",
volume = "80",
pages = "497--505",
journal = "Cancer Chemotherapy and Pharmacology",
issn = "0344-5704",
publisher = "Springer Verlag",
number = "3",

}

TY - JOUR

T1 - A phase II trial of erlotinib monotherapy in advanced pancreatic cancer as a first- or second-line agent

AU - Fountzilas, Christos

AU - Chhatrala, Ravi

AU - Khushalani, Nikhil

AU - Tan, Wei

AU - LeVea, Charles

AU - Hutson, Alan

AU - Tucker, Chris

AU - Ma, Wen Wee

AU - Warren, Graham

AU - Boland, Patrick

AU - Iyer, Renuka

PY - 2017/9/1

Y1 - 2017/9/1

N2 - Introduction: Pancreatic adenocarcinoma carries a grim prognosis. In 2007, gemcitabine with erlotinib emerged as an appropriate treatment option for patients with advanced inoperable or metastatic disease (APC). In this phase II trial we sought to evaluate the efficacy of erlotinib monotherapy in patients with APC who had disease refractory to or ineligibility for gemcitabine-based therapy. Methods: Eligible patients who had received 0 or 1 non-EGFR inhibitor containing gemcitabine-based chemotherapy for APC were recruited prospectively and treated with erlotinib 150 mg orally daily until unacceptable toxicity or disease progression. Primary endpoint was progression-free survival (PFS). Correlations of clinical response with smoking, rash, steady-state concentration of erlotinib and its metabolite (OSI-420) as well as the nicotine metabolite cotinine were performed. Results: The trial was terminated early for futility. Eighteen of the 34 planned subjects were recruited. Median PFS and OS were 42 and 95 days, respectively. Best response was stable disease (21%). There was a trend for improved PFS and OS in never smokers compared to current and past smokers (128.5, 39, 42 days and 173, 100, 88 days, respectively). Past/current smokers had lower steady-state concentrations of erlotinib and OSI-420 compared to never smokers. There was evidence of recent smoking exposure in 30% of patients self-identified as past smokers. Rash was infrequent, with no cases of grade III/IV rash and it was not related to treatment outcomes. Conclusions: Overall, erlotinib monotherapy failed to improve outcomes compared to historical controls in patients with APC after 0–1 prior systemic therapies. There was a trend for improved PFS and OS in never smokers.

AB - Introduction: Pancreatic adenocarcinoma carries a grim prognosis. In 2007, gemcitabine with erlotinib emerged as an appropriate treatment option for patients with advanced inoperable or metastatic disease (APC). In this phase II trial we sought to evaluate the efficacy of erlotinib monotherapy in patients with APC who had disease refractory to or ineligibility for gemcitabine-based therapy. Methods: Eligible patients who had received 0 or 1 non-EGFR inhibitor containing gemcitabine-based chemotherapy for APC were recruited prospectively and treated with erlotinib 150 mg orally daily until unacceptable toxicity or disease progression. Primary endpoint was progression-free survival (PFS). Correlations of clinical response with smoking, rash, steady-state concentration of erlotinib and its metabolite (OSI-420) as well as the nicotine metabolite cotinine were performed. Results: The trial was terminated early for futility. Eighteen of the 34 planned subjects were recruited. Median PFS and OS were 42 and 95 days, respectively. Best response was stable disease (21%). There was a trend for improved PFS and OS in never smokers compared to current and past smokers (128.5, 39, 42 days and 173, 100, 88 days, respectively). Past/current smokers had lower steady-state concentrations of erlotinib and OSI-420 compared to never smokers. There was evidence of recent smoking exposure in 30% of patients self-identified as past smokers. Rash was infrequent, with no cases of grade III/IV rash and it was not related to treatment outcomes. Conclusions: Overall, erlotinib monotherapy failed to improve outcomes compared to historical controls in patients with APC after 0–1 prior systemic therapies. There was a trend for improved PFS and OS in never smokers.

KW - Cotinine

KW - Erlotinib

KW - Pancreatic cancer

KW - Smoking

UR - http://www.scopus.com/inward/record.url?scp=85023177201&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85023177201&partnerID=8YFLogxK

U2 - 10.1007/s00280-017-3375-9

DO - 10.1007/s00280-017-3375-9

M3 - Article

C2 - 28702772

AN - SCOPUS:85023177201

VL - 80

SP - 497

EP - 505

JO - Cancer Chemotherapy and Pharmacology

JF - Cancer Chemotherapy and Pharmacology

SN - 0344-5704

IS - 3

ER -