Phase I trial of gemcitabine and paclitaxel in advanced solid tumors

Nelson Lim, Primo N Lara, Derick H Lau, Martin J. Edelman, Michael Tanaka, Ghassan Al-Jazayrly, Joan Houston, Ignacio Lauder, David R Gandara

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Purpose. Gemcitabine and paclitaxel are chemotherapeutic agents with clinical antitumor activity in a broad range of malignant solid tumors. Because of preclinical synergy, unique mechanisms of action and resistance, and nonoverlapping toxicities, gemcitabine and paclitaxel combinations are attractive for testing in clinical trials. Prior weekly gemcitabine and paclitaxel regimens administered on a 28-day cycle have been limited by cumulative hematological toxicity on day-15, thus reducing the planned gemcitabine dose intensity. We therefore conducted a phase I trial of a 21-day schedule of weekly gemcitabine and paclitaxel to determine the tolerability, maximum tolerated dose (MTD), and preliminary estimates of efficacy of this regimen. Patients and Methods. Forty-one patients with advanced malignant solid tumors were accrued. Gemcitabine was given at a fixed dose of 1000mg/m2 while paclitaxel was administered at an initial dose of 60 mg/m2, then escalated by 15 mg/m2 increments over seven dose levels to a prospectively planned maximum dose of 150 mg/m2. Both agents were infused intravenously on days one and eight every 21 days. At least three patients were enrolled per dose level. No intrapatient dose escalation was allowed. Results. All patients were assessable for toxicity and 31 were assessable for response. The regimen was generally well-tolerated. Dose-limiting thrombocytopenia was observed in one patient at a paclitaxel dose of 135 mg/m2/week (dose level 6). After expansion of this dose level by 14 additional patients, no further dose-limiting toxicities were observed although one patient at dose level seven died of neutropenic sepsis after completing three cycles. There were eight partial responders for an overall response proportion of 26% (95% CI: 11, 41). Twelve patients (39%) had stable disease. Conclusion. This 21-day schedule of gemcitabine and paclitaxel is safe, well-tolerated, and active. The recommended phase II dose is gemcitabine 1000 mg/m2 and paclitaxel 150 mg/m2 on days one and eight every 21 days. The antitumor activity observed with this regimen warrants further investigation.

Original languageEnglish (US)
Pages (from-to)7-13
Number of pages7
JournalCancer Investigation
Volume21
Issue number1
DOIs
StatePublished - 2003

Fingerprint

gemcitabine
Paclitaxel
Neoplasms
Appointments and Schedules
Maximum Tolerated Dose
Thrombocytopenia
Sepsis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase I trial of gemcitabine and paclitaxel in advanced solid tumors. / Lim, Nelson; Lara, Primo N; Lau, Derick H; Edelman, Martin J.; Tanaka, Michael; Al-Jazayrly, Ghassan; Houston, Joan; Lauder, Ignacio; Gandara, David R.

In: Cancer Investigation, Vol. 21, No. 1, 2003, p. 7-13.

Research output: Contribution to journalArticle

Lim, Nelson ; Lara, Primo N ; Lau, Derick H ; Edelman, Martin J. ; Tanaka, Michael ; Al-Jazayrly, Ghassan ; Houston, Joan ; Lauder, Ignacio ; Gandara, David R. / Phase I trial of gemcitabine and paclitaxel in advanced solid tumors. In: Cancer Investigation. 2003 ; Vol. 21, No. 1. pp. 7-13.
@article{065f4858220a43e687ccf94533e8b3cd,
title = "Phase I trial of gemcitabine and paclitaxel in advanced solid tumors",
abstract = "Purpose. Gemcitabine and paclitaxel are chemotherapeutic agents with clinical antitumor activity in a broad range of malignant solid tumors. Because of preclinical synergy, unique mechanisms of action and resistance, and nonoverlapping toxicities, gemcitabine and paclitaxel combinations are attractive for testing in clinical trials. Prior weekly gemcitabine and paclitaxel regimens administered on a 28-day cycle have been limited by cumulative hematological toxicity on day-15, thus reducing the planned gemcitabine dose intensity. We therefore conducted a phase I trial of a 21-day schedule of weekly gemcitabine and paclitaxel to determine the tolerability, maximum tolerated dose (MTD), and preliminary estimates of efficacy of this regimen. Patients and Methods. Forty-one patients with advanced malignant solid tumors were accrued. Gemcitabine was given at a fixed dose of 1000mg/m2 while paclitaxel was administered at an initial dose of 60 mg/m2, then escalated by 15 mg/m2 increments over seven dose levels to a prospectively planned maximum dose of 150 mg/m2. Both agents were infused intravenously on days one and eight every 21 days. At least three patients were enrolled per dose level. No intrapatient dose escalation was allowed. Results. All patients were assessable for toxicity and 31 were assessable for response. The regimen was generally well-tolerated. Dose-limiting thrombocytopenia was observed in one patient at a paclitaxel dose of 135 mg/m2/week (dose level 6). After expansion of this dose level by 14 additional patients, no further dose-limiting toxicities were observed although one patient at dose level seven died of neutropenic sepsis after completing three cycles. There were eight partial responders for an overall response proportion of 26{\%} (95{\%} CI: 11, 41). Twelve patients (39{\%}) had stable disease. Conclusion. This 21-day schedule of gemcitabine and paclitaxel is safe, well-tolerated, and active. The recommended phase II dose is gemcitabine 1000 mg/m2 and paclitaxel 150 mg/m2 on days one and eight every 21 days. The antitumor activity observed with this regimen warrants further investigation.",
author = "Nelson Lim and Lara, {Primo N} and Lau, {Derick H} and Edelman, {Martin J.} and Michael Tanaka and Ghassan Al-Jazayrly and Joan Houston and Ignacio Lauder and Gandara, {David R}",
year = "2003",
doi = "10.1081/CNV-120016398",
language = "English (US)",
volume = "21",
pages = "7--13",
journal = "Cancer Investigation",
issn = "0735-7907",
publisher = "Informa Healthcare",
number = "1",

}

TY - JOUR

T1 - Phase I trial of gemcitabine and paclitaxel in advanced solid tumors

AU - Lim, Nelson

AU - Lara, Primo N

AU - Lau, Derick H

AU - Edelman, Martin J.

AU - Tanaka, Michael

AU - Al-Jazayrly, Ghassan

AU - Houston, Joan

AU - Lauder, Ignacio

AU - Gandara, David R

PY - 2003

Y1 - 2003

N2 - Purpose. Gemcitabine and paclitaxel are chemotherapeutic agents with clinical antitumor activity in a broad range of malignant solid tumors. Because of preclinical synergy, unique mechanisms of action and resistance, and nonoverlapping toxicities, gemcitabine and paclitaxel combinations are attractive for testing in clinical trials. Prior weekly gemcitabine and paclitaxel regimens administered on a 28-day cycle have been limited by cumulative hematological toxicity on day-15, thus reducing the planned gemcitabine dose intensity. We therefore conducted a phase I trial of a 21-day schedule of weekly gemcitabine and paclitaxel to determine the tolerability, maximum tolerated dose (MTD), and preliminary estimates of efficacy of this regimen. Patients and Methods. Forty-one patients with advanced malignant solid tumors were accrued. Gemcitabine was given at a fixed dose of 1000mg/m2 while paclitaxel was administered at an initial dose of 60 mg/m2, then escalated by 15 mg/m2 increments over seven dose levels to a prospectively planned maximum dose of 150 mg/m2. Both agents were infused intravenously on days one and eight every 21 days. At least three patients were enrolled per dose level. No intrapatient dose escalation was allowed. Results. All patients were assessable for toxicity and 31 were assessable for response. The regimen was generally well-tolerated. Dose-limiting thrombocytopenia was observed in one patient at a paclitaxel dose of 135 mg/m2/week (dose level 6). After expansion of this dose level by 14 additional patients, no further dose-limiting toxicities were observed although one patient at dose level seven died of neutropenic sepsis after completing three cycles. There were eight partial responders for an overall response proportion of 26% (95% CI: 11, 41). Twelve patients (39%) had stable disease. Conclusion. This 21-day schedule of gemcitabine and paclitaxel is safe, well-tolerated, and active. The recommended phase II dose is gemcitabine 1000 mg/m2 and paclitaxel 150 mg/m2 on days one and eight every 21 days. The antitumor activity observed with this regimen warrants further investigation.

AB - Purpose. Gemcitabine and paclitaxel are chemotherapeutic agents with clinical antitumor activity in a broad range of malignant solid tumors. Because of preclinical synergy, unique mechanisms of action and resistance, and nonoverlapping toxicities, gemcitabine and paclitaxel combinations are attractive for testing in clinical trials. Prior weekly gemcitabine and paclitaxel regimens administered on a 28-day cycle have been limited by cumulative hematological toxicity on day-15, thus reducing the planned gemcitabine dose intensity. We therefore conducted a phase I trial of a 21-day schedule of weekly gemcitabine and paclitaxel to determine the tolerability, maximum tolerated dose (MTD), and preliminary estimates of efficacy of this regimen. Patients and Methods. Forty-one patients with advanced malignant solid tumors were accrued. Gemcitabine was given at a fixed dose of 1000mg/m2 while paclitaxel was administered at an initial dose of 60 mg/m2, then escalated by 15 mg/m2 increments over seven dose levels to a prospectively planned maximum dose of 150 mg/m2. Both agents were infused intravenously on days one and eight every 21 days. At least three patients were enrolled per dose level. No intrapatient dose escalation was allowed. Results. All patients were assessable for toxicity and 31 were assessable for response. The regimen was generally well-tolerated. Dose-limiting thrombocytopenia was observed in one patient at a paclitaxel dose of 135 mg/m2/week (dose level 6). After expansion of this dose level by 14 additional patients, no further dose-limiting toxicities were observed although one patient at dose level seven died of neutropenic sepsis after completing three cycles. There were eight partial responders for an overall response proportion of 26% (95% CI: 11, 41). Twelve patients (39%) had stable disease. Conclusion. This 21-day schedule of gemcitabine and paclitaxel is safe, well-tolerated, and active. The recommended phase II dose is gemcitabine 1000 mg/m2 and paclitaxel 150 mg/m2 on days one and eight every 21 days. The antitumor activity observed with this regimen warrants further investigation.

UR - http://www.scopus.com/inward/record.url?scp=0037215034&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037215034&partnerID=8YFLogxK

U2 - 10.1081/CNV-120016398

DO - 10.1081/CNV-120016398

M3 - Article

C2 - 12643004

AN - SCOPUS:0037215034

VL - 21

SP - 7

EP - 13

JO - Cancer Investigation

JF - Cancer Investigation

SN - 0735-7907

IS - 1

ER -