A phase I study of sequential administration of escalating doses of intravenous paclitaxel, oral topotecan, and fixed-dose oral etoposide in patients with solid tumors

Caio M S Rocha Lima, Carlo V. Catapano, Daniel Pacheco, Carol A. Sherman, Greg Oakhill, Chaudhry Mushtaq, Kimberly D. Freeman, Mark R. Green

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

BACKGROUND. Based on preclinical findings and on the clinical antitumor efficacy of sequential paclitaxel/topotecan and topotecan/etoposide, the authors sought to define the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) associated with a sequential combination of paclitaxel, topotecan, and etoposide in patients with solid tumors. METHODS. The MTDs were determined through standard dose escalation in cohorts of three patients. Patients with refractory solid tumors and performance status ≤ 2 were treated with intravenous paclitaxel 50-110 mg/m2 (Day 1), oral topotecan 0.5-2.0 mg/m2 (Days 2-4), and oral etoposide 160 mg/m 2 (Days 5-7) during every 21-day cycle. For dose-limiting neutropenia, granulocyte-colony-stimulating factor (G-CSF) was administered on Day 8 in subsequent cohorts. Blood samples were obtained before treatment during Cycle 1 (Days 1, 2, and 5) for topoisomerase I assessment. RESULTS. Twenty-eight patients received a combined total of 129 cycles. The MTDs were paclitaxel 80 mg/m2, topotecan 1.5 mg/m2, and etoposide 160 mg/m2 without G-CSF. In minimally pretreated patients, G-CSF allowed paclitaxel dose escalation to 110 mg/m2. Three patients (11%) had radiologic partial responses, and 4 patients (14%) had stable disease. Day 2 topoisomerase I levels increased by 2-15 times relative to baseline levels in 7 of 14 patients analyzed (50%). CONCLUSIONS. The novel sequential combination that was evaluated generally was well tolerated and active in patients with refractory solid tumors. Based on hematologic DLTs, the authors recommend further evaluation of paclitaxel 110 mg/m2, topotecan 1.5 mg/m 2, and etoposide 160 mg/m2 with G-CSF support in minimally pretreated patients.

Original languageEnglish
Pages (from-to)2671-2679
Number of pages9
JournalCancer
Volume100
Issue number12
DOIs
StatePublished - Jun 15 2004

Fingerprint

Topotecan
Etoposide
Paclitaxel
Granulocyte Colony-Stimulating Factor
Neoplasms
Maximum Tolerated Dose
Type I DNA Topoisomerase
Neutropenia

Keywords

  • Combination chemotherapy
  • Etoposide
  • Lung carcinoma
  • Paclitaxel
  • Phase I trial
  • Topotecan

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Rocha Lima, C. M. S., Catapano, C. V., Pacheco, D., Sherman, C. A., Oakhill, G., Mushtaq, C., ... Green, M. R. (2004). A phase I study of sequential administration of escalating doses of intravenous paclitaxel, oral topotecan, and fixed-dose oral etoposide in patients with solid tumors. Cancer, 100(12), 2671-2679. https://doi.org/10.1002/cncr.20330

A phase I study of sequential administration of escalating doses of intravenous paclitaxel, oral topotecan, and fixed-dose oral etoposide in patients with solid tumors. / Rocha Lima, Caio M S; Catapano, Carlo V.; Pacheco, Daniel; Sherman, Carol A.; Oakhill, Greg; Mushtaq, Chaudhry; Freeman, Kimberly D.; Green, Mark R.

In: Cancer, Vol. 100, No. 12, 15.06.2004, p. 2671-2679.

Research output: Contribution to journalArticle

Rocha Lima, CMS, Catapano, CV, Pacheco, D, Sherman, CA, Oakhill, G, Mushtaq, C, Freeman, KD & Green, MR 2004, 'A phase I study of sequential administration of escalating doses of intravenous paclitaxel, oral topotecan, and fixed-dose oral etoposide in patients with solid tumors', Cancer, vol. 100, no. 12, pp. 2671-2679. https://doi.org/10.1002/cncr.20330
Rocha Lima, Caio M S ; Catapano, Carlo V. ; Pacheco, Daniel ; Sherman, Carol A. ; Oakhill, Greg ; Mushtaq, Chaudhry ; Freeman, Kimberly D. ; Green, Mark R. / A phase I study of sequential administration of escalating doses of intravenous paclitaxel, oral topotecan, and fixed-dose oral etoposide in patients with solid tumors. In: Cancer. 2004 ; Vol. 100, No. 12. pp. 2671-2679.
@article{e068f3b6266a4360a12521a623905a2b,
title = "A phase I study of sequential administration of escalating doses of intravenous paclitaxel, oral topotecan, and fixed-dose oral etoposide in patients with solid tumors",
abstract = "BACKGROUND. Based on preclinical findings and on the clinical antitumor efficacy of sequential paclitaxel/topotecan and topotecan/etoposide, the authors sought to define the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) associated with a sequential combination of paclitaxel, topotecan, and etoposide in patients with solid tumors. METHODS. The MTDs were determined through standard dose escalation in cohorts of three patients. Patients with refractory solid tumors and performance status ≤ 2 were treated with intravenous paclitaxel 50-110 mg/m2 (Day 1), oral topotecan 0.5-2.0 mg/m2 (Days 2-4), and oral etoposide 160 mg/m 2 (Days 5-7) during every 21-day cycle. For dose-limiting neutropenia, granulocyte-colony-stimulating factor (G-CSF) was administered on Day 8 in subsequent cohorts. Blood samples were obtained before treatment during Cycle 1 (Days 1, 2, and 5) for topoisomerase I assessment. RESULTS. Twenty-eight patients received a combined total of 129 cycles. The MTDs were paclitaxel 80 mg/m2, topotecan 1.5 mg/m2, and etoposide 160 mg/m2 without G-CSF. In minimally pretreated patients, G-CSF allowed paclitaxel dose escalation to 110 mg/m2. Three patients (11{\%}) had radiologic partial responses, and 4 patients (14{\%}) had stable disease. Day 2 topoisomerase I levels increased by 2-15 times relative to baseline levels in 7 of 14 patients analyzed (50{\%}). CONCLUSIONS. The novel sequential combination that was evaluated generally was well tolerated and active in patients with refractory solid tumors. Based on hematologic DLTs, the authors recommend further evaluation of paclitaxel 110 mg/m2, topotecan 1.5 mg/m 2, and etoposide 160 mg/m2 with G-CSF support in minimally pretreated patients.",
keywords = "Combination chemotherapy, Etoposide, Lung carcinoma, Paclitaxel, Phase I trial, Topotecan",
author = "{Rocha Lima}, {Caio M S} and Catapano, {Carlo V.} and Daniel Pacheco and Sherman, {Carol A.} and Greg Oakhill and Chaudhry Mushtaq and Freeman, {Kimberly D.} and Green, {Mark R.}",
year = "2004",
month = "6",
day = "15",
doi = "10.1002/cncr.20330",
language = "English",
volume = "100",
pages = "2671--2679",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "12",

}

TY - JOUR

T1 - A phase I study of sequential administration of escalating doses of intravenous paclitaxel, oral topotecan, and fixed-dose oral etoposide in patients with solid tumors

AU - Rocha Lima, Caio M S

AU - Catapano, Carlo V.

AU - Pacheco, Daniel

AU - Sherman, Carol A.

AU - Oakhill, Greg

AU - Mushtaq, Chaudhry

AU - Freeman, Kimberly D.

AU - Green, Mark R.

PY - 2004/6/15

Y1 - 2004/6/15

N2 - BACKGROUND. Based on preclinical findings and on the clinical antitumor efficacy of sequential paclitaxel/topotecan and topotecan/etoposide, the authors sought to define the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) associated with a sequential combination of paclitaxel, topotecan, and etoposide in patients with solid tumors. METHODS. The MTDs were determined through standard dose escalation in cohorts of three patients. Patients with refractory solid tumors and performance status ≤ 2 were treated with intravenous paclitaxel 50-110 mg/m2 (Day 1), oral topotecan 0.5-2.0 mg/m2 (Days 2-4), and oral etoposide 160 mg/m 2 (Days 5-7) during every 21-day cycle. For dose-limiting neutropenia, granulocyte-colony-stimulating factor (G-CSF) was administered on Day 8 in subsequent cohorts. Blood samples were obtained before treatment during Cycle 1 (Days 1, 2, and 5) for topoisomerase I assessment. RESULTS. Twenty-eight patients received a combined total of 129 cycles. The MTDs were paclitaxel 80 mg/m2, topotecan 1.5 mg/m2, and etoposide 160 mg/m2 without G-CSF. In minimally pretreated patients, G-CSF allowed paclitaxel dose escalation to 110 mg/m2. Three patients (11%) had radiologic partial responses, and 4 patients (14%) had stable disease. Day 2 topoisomerase I levels increased by 2-15 times relative to baseline levels in 7 of 14 patients analyzed (50%). CONCLUSIONS. The novel sequential combination that was evaluated generally was well tolerated and active in patients with refractory solid tumors. Based on hematologic DLTs, the authors recommend further evaluation of paclitaxel 110 mg/m2, topotecan 1.5 mg/m 2, and etoposide 160 mg/m2 with G-CSF support in minimally pretreated patients.

AB - BACKGROUND. Based on preclinical findings and on the clinical antitumor efficacy of sequential paclitaxel/topotecan and topotecan/etoposide, the authors sought to define the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) associated with a sequential combination of paclitaxel, topotecan, and etoposide in patients with solid tumors. METHODS. The MTDs were determined through standard dose escalation in cohorts of three patients. Patients with refractory solid tumors and performance status ≤ 2 were treated with intravenous paclitaxel 50-110 mg/m2 (Day 1), oral topotecan 0.5-2.0 mg/m2 (Days 2-4), and oral etoposide 160 mg/m 2 (Days 5-7) during every 21-day cycle. For dose-limiting neutropenia, granulocyte-colony-stimulating factor (G-CSF) was administered on Day 8 in subsequent cohorts. Blood samples were obtained before treatment during Cycle 1 (Days 1, 2, and 5) for topoisomerase I assessment. RESULTS. Twenty-eight patients received a combined total of 129 cycles. The MTDs were paclitaxel 80 mg/m2, topotecan 1.5 mg/m2, and etoposide 160 mg/m2 without G-CSF. In minimally pretreated patients, G-CSF allowed paclitaxel dose escalation to 110 mg/m2. Three patients (11%) had radiologic partial responses, and 4 patients (14%) had stable disease. Day 2 topoisomerase I levels increased by 2-15 times relative to baseline levels in 7 of 14 patients analyzed (50%). CONCLUSIONS. The novel sequential combination that was evaluated generally was well tolerated and active in patients with refractory solid tumors. Based on hematologic DLTs, the authors recommend further evaluation of paclitaxel 110 mg/m2, topotecan 1.5 mg/m 2, and etoposide 160 mg/m2 with G-CSF support in minimally pretreated patients.

KW - Combination chemotherapy

KW - Etoposide

KW - Lung carcinoma

KW - Paclitaxel

KW - Phase I trial

KW - Topotecan

UR - http://www.scopus.com/inward/record.url?scp=2642565158&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2642565158&partnerID=8YFLogxK

U2 - 10.1002/cncr.20330

DO - 10.1002/cncr.20330

M3 - Article

C2 - 15197811

AN - SCOPUS:2642565158

VL - 100

SP - 2671

EP - 2679

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 12

ER -