Paclitaxel Combined With 5-FU and Cisplatin Concomitant With Radiotherapy in the Management of Locally Advanced or Metastatic Esophageal Cancer (Adenocarcinoma and Squamous Histologies) - A Phase I/Modified Phase II Trial
OBJECTIVES: I. Define the maximum tolerated dose (MTD) of paclitaxel (TAX) when given as a 3
hour infusion in combination with cisplatin (CDDP), fluorouracil (5-FU), and radiation
therapy. II. Define the toxicity profile of TAX when given as a 3 hour infusion in
combination with CDDP, 5-FU, and radiation therapy. III. Evaluate the effectiveness of a TAX
containing chemotherapy regimen and concurrent radiotherapy followed by resection in the
treatment of locally advanced esophageal cancer as judged by the complete response rate,
pathological complete response rate, time to recurrence, and overall survival.
OUTLINE: Patients receive radiation to the tumor and nodal area 5 days a week for 5 weeks.
Patients receive chemotherapy consisting of cisplatin (CDDP) via rapid intravenous infusion
on day 1 followed by fluorouracil (5-FU) via 96-hour continuous infusion (CI) on days 1
through 4; this is repeated on the last 4 days of radiation therapy (days 29-31), with an
additional dose of CDDP on day 29 and a 96-hour CI of 5-FU on days 29-31. Patients also
receive paclitaxel (TAX) as a weekly 3 hour infusion on days 1, 8, 15, and 29, with 3
patients treated at each dose level and subsequent patients treated according to the
toxicity observed in previous cohorts. TAX will be given prior to the CDDP and 5-FU on the
weeks when it is given concurrently. The MTD of TAX is defined as the dose at which no more
than 1 of 6 patients experiences dose-limiting toxicity. Surgical resection takes place 2-8
weeks following completion of chemoradiotherapy in all patients except those with disease
progression and those who are surgically unresectable or medically unfit (includes those
with metastatic disease) to tolerate surgery. An additional course of TAX/CDDP/5-FU is given
28-35 days after surgery.
PROJECTED ACCRUAL: Three patients will be entered into the lowest dose level of TAX, and 3-6
patients entered into up to three additional dose levels of TAX for the phase I study. An
additional group of up to 11 patients will be accrued for the first stage of the modified
phase II study and 38 to the second stage, if warranted. The study will be completed within
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose
Define the maximum tolerated dose of paclitaxel when given as a 3-hour infusion in combination with cisplatin, 5-FU, and radiation therapy. The MTD will be defined as the dose level immediately below that which caused dose limiting toxicity (DLT) in a third or more of the patients in any cohort.
Stephen A. Bernard, MD
UNC Lineberger Comprehensive Cancer Center
United States: Federal Government
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