A phase II trial of perifosine in locally advanced, unresectable, or metastatic pancreatic adenocarcinoma

Robert De W Marsh, C. M Rocha Lima, D. E. Levy, E. P. Mitchell, K. M. Rowland, A. B. Benson

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

BACKGROUND: Perifosine, a heterocyclic alkylphosphocholine signal transduction inhibitor, has activity against multiple cell types in vitro. This is a phase II study to determine activity and toxicity of perifosine in pancreatic adenocarcinoma. PATIENTS AND METHODS: Previously untreated patients with locally advanced, unresectable, or metastatic pancreatic adenocarcinoma, performance status Eastern Cooperative Oncology Group 0 or 1, were enrolled. An oral loading dose of 900 mg was followed by 100 mg per day until progression or unacceptable toxicity. Response criteria in solid tumors (RECIST) methodology and a 2-stage design were used. Suspension could occur for inadequate response in the first cohort or for more than 25% grade 3 or greater toxicity. RESULTS: Ten patients were enrolled. Six received 1 month and 4 received 2 months of treatment. Four discontinued therapy as a result of progression and 2 because of clinical deterioration. Three died during treatment. One patient had stable disease but discontinued therapy as a result of unacceptable adverse events (95% confidence interval: 0.3-45%). There were no objective responses and all patients died of progressive disease. Median overall and progression-free survival was 1.85 months (95% confidence interval: 0.9-2.7) and 1.5 months (95% confidence interval: 0.9-1.9) respectively. CONCLUSION: The study was suspended and subsequently terminated as a result of unacceptable adverse events during the first stage. Perifosine does not appear to be worthy of further study in this group of patients.

Original languageEnglish
Pages (from-to)26-31
Number of pages6
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume30
Issue number1
DOIs
StatePublished - Feb 1 2007

Fingerprint

Adenocarcinoma
Confidence Intervals
Therapeutics
Disease-Free Survival
Signal Transduction
Suspensions
perifosine
Neoplasms

Keywords

  • Adenocarcinoma
  • Alkylphosphocholine
  • Pancreas
  • Perifosine
  • Phase II
  • Unresectable

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A phase II trial of perifosine in locally advanced, unresectable, or metastatic pancreatic adenocarcinoma. / Marsh, Robert De W; Lima, C. M Rocha; Levy, D. E.; Mitchell, E. P.; Rowland, K. M.; Benson, A. B.

In: American Journal of Clinical Oncology: Cancer Clinical Trials, Vol. 30, No. 1, 01.02.2007, p. 26-31.

Research output: Contribution to journalArticle

Marsh, Robert De W ; Lima, C. M Rocha ; Levy, D. E. ; Mitchell, E. P. ; Rowland, K. M. ; Benson, A. B. / A phase II trial of perifosine in locally advanced, unresectable, or metastatic pancreatic adenocarcinoma. In: American Journal of Clinical Oncology: Cancer Clinical Trials. 2007 ; Vol. 30, No. 1. pp. 26-31.
@article{03093aba27c440fa8be2344186a5ffdd,
title = "A phase II trial of perifosine in locally advanced, unresectable, or metastatic pancreatic adenocarcinoma",
abstract = "BACKGROUND: Perifosine, a heterocyclic alkylphosphocholine signal transduction inhibitor, has activity against multiple cell types in vitro. This is a phase II study to determine activity and toxicity of perifosine in pancreatic adenocarcinoma. PATIENTS AND METHODS: Previously untreated patients with locally advanced, unresectable, or metastatic pancreatic adenocarcinoma, performance status Eastern Cooperative Oncology Group 0 or 1, were enrolled. An oral loading dose of 900 mg was followed by 100 mg per day until progression or unacceptable toxicity. Response criteria in solid tumors (RECIST) methodology and a 2-stage design were used. Suspension could occur for inadequate response in the first cohort or for more than 25{\%} grade 3 or greater toxicity. RESULTS: Ten patients were enrolled. Six received 1 month and 4 received 2 months of treatment. Four discontinued therapy as a result of progression and 2 because of clinical deterioration. Three died during treatment. One patient had stable disease but discontinued therapy as a result of unacceptable adverse events (95{\%} confidence interval: 0.3-45{\%}). There were no objective responses and all patients died of progressive disease. Median overall and progression-free survival was 1.85 months (95{\%} confidence interval: 0.9-2.7) and 1.5 months (95{\%} confidence interval: 0.9-1.9) respectively. CONCLUSION: The study was suspended and subsequently terminated as a result of unacceptable adverse events during the first stage. Perifosine does not appear to be worthy of further study in this group of patients.",
keywords = "Adenocarcinoma, Alkylphosphocholine, Pancreas, Perifosine, Phase II, Unresectable",
author = "Marsh, {Robert De W} and Lima, {C. M Rocha} and Levy, {D. E.} and Mitchell, {E. P.} and Rowland, {K. M.} and Benson, {A. B.}",
year = "2007",
month = "2",
day = "1",
doi = "10.1097/01.coc.0000251235.46149.43",
language = "English",
volume = "30",
pages = "26--31",
journal = "American Journal of Clinical Oncology",
issn = "0277-3732",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - A phase II trial of perifosine in locally advanced, unresectable, or metastatic pancreatic adenocarcinoma

AU - Marsh, Robert De W

AU - Lima, C. M Rocha

AU - Levy, D. E.

AU - Mitchell, E. P.

AU - Rowland, K. M.

AU - Benson, A. B.

PY - 2007/2/1

Y1 - 2007/2/1

N2 - BACKGROUND: Perifosine, a heterocyclic alkylphosphocholine signal transduction inhibitor, has activity against multiple cell types in vitro. This is a phase II study to determine activity and toxicity of perifosine in pancreatic adenocarcinoma. PATIENTS AND METHODS: Previously untreated patients with locally advanced, unresectable, or metastatic pancreatic adenocarcinoma, performance status Eastern Cooperative Oncology Group 0 or 1, were enrolled. An oral loading dose of 900 mg was followed by 100 mg per day until progression or unacceptable toxicity. Response criteria in solid tumors (RECIST) methodology and a 2-stage design were used. Suspension could occur for inadequate response in the first cohort or for more than 25% grade 3 or greater toxicity. RESULTS: Ten patients were enrolled. Six received 1 month and 4 received 2 months of treatment. Four discontinued therapy as a result of progression and 2 because of clinical deterioration. Three died during treatment. One patient had stable disease but discontinued therapy as a result of unacceptable adverse events (95% confidence interval: 0.3-45%). There were no objective responses and all patients died of progressive disease. Median overall and progression-free survival was 1.85 months (95% confidence interval: 0.9-2.7) and 1.5 months (95% confidence interval: 0.9-1.9) respectively. CONCLUSION: The study was suspended and subsequently terminated as a result of unacceptable adverse events during the first stage. Perifosine does not appear to be worthy of further study in this group of patients.

AB - BACKGROUND: Perifosine, a heterocyclic alkylphosphocholine signal transduction inhibitor, has activity against multiple cell types in vitro. This is a phase II study to determine activity and toxicity of perifosine in pancreatic adenocarcinoma. PATIENTS AND METHODS: Previously untreated patients with locally advanced, unresectable, or metastatic pancreatic adenocarcinoma, performance status Eastern Cooperative Oncology Group 0 or 1, were enrolled. An oral loading dose of 900 mg was followed by 100 mg per day until progression or unacceptable toxicity. Response criteria in solid tumors (RECIST) methodology and a 2-stage design were used. Suspension could occur for inadequate response in the first cohort or for more than 25% grade 3 or greater toxicity. RESULTS: Ten patients were enrolled. Six received 1 month and 4 received 2 months of treatment. Four discontinued therapy as a result of progression and 2 because of clinical deterioration. Three died during treatment. One patient had stable disease but discontinued therapy as a result of unacceptable adverse events (95% confidence interval: 0.3-45%). There were no objective responses and all patients died of progressive disease. Median overall and progression-free survival was 1.85 months (95% confidence interval: 0.9-2.7) and 1.5 months (95% confidence interval: 0.9-1.9) respectively. CONCLUSION: The study was suspended and subsequently terminated as a result of unacceptable adverse events during the first stage. Perifosine does not appear to be worthy of further study in this group of patients.

KW - Adenocarcinoma

KW - Alkylphosphocholine

KW - Pancreas

KW - Perifosine

KW - Phase II

KW - Unresectable

UR - http://www.scopus.com/inward/record.url?scp=33846785219&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846785219&partnerID=8YFLogxK

U2 - 10.1097/01.coc.0000251235.46149.43

DO - 10.1097/01.coc.0000251235.46149.43

M3 - Article

C2 - 17278891

AN - SCOPUS:33846785219

VL - 30

SP - 26

EP - 31

JO - American Journal of Clinical Oncology

JF - American Journal of Clinical Oncology

SN - 0277-3732

IS - 1

ER -