A Phase II trial of epothilone B analogue BMS-247550 (NSC #710428) ixabepilone, in patients with advanced pancreas cancer: a Southwest Oncology Group study.
OBJECTIVE
The purpose of this Phase II multi-institutional study was to define the efficacy and toxicity of ixabepilone in patients with advance pancreatic adenocarcinoma.


METHODS
Patients were required to have pancreatic adenocarcinoma and metastatic or recurrent disease that was not amenable to curative resection. Performance status was 0-1, and patients could not have had prior chemotherapy, or chemoradiation therapy for their advanced disease although prior local palliative radiation was allowed. Ixabepilone was administered iv as a 3 hour infusion every 21 days. Initially, the dose was 50 mg/m(2) but this was lowered to 40 mg/m(2) shortly after the trial opened because of concerns about neurotoxicity.


RESULTS
Sixty-two patients were registered however 2 were ineligible because they did not have recurrent or metastatic disease. For the 60 eligible patients, 22 had performance status of 0 and 38 performance status of 1. The estimated 6-month survival was 60% (95% CI 48%-72%) with a median survival of 7.2 months and an estimated time to treatment failure of 2.3 months. Out of 56 patients with measurable disease there were 5 confirmed partial responses for a confirmed response probability of 9% (95% CI 3%-20%) and 7 unconfirmed partial responses for an overall response probability of 21% (95% CI 12%-34%). Common toxicities were neutropenia/granulocytopenia, nausea and vomiting and neuropathy. There was one death, cause not determined but judged "possibly" related to treatment.


CONCLUSIONS
Ixabepilone shows encouraging activity in patients with advanced pancreatic cancer and should be investigated further in this disease.
Whitehead
Robert P
RP
Department of Internal Medicine, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555-0565, USA. rpwhiteh@utmb.edu
McCoy
Sheryl
S
Rivkin
Saul E
SE
Gross
Howard M
HM
Conrad
Marcel E
ME
Doolittle
Gary C
GC
Wolff
Robert A
RA
Goodwin
J Wendall
JW
Dakhil
Shaker R
SR
Abbruzzese
James L
JL
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D034261:Epothilones / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome; D050257:Tubulin Modulators / Q000009:adverse effects / Q000627:therapeutic use*
D034261:Epothilones; D050257:Tubulin Modulators; C430592:ixabepilone