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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. 2004 Jun 15; 100(12):2671-9.C

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 < or = 2 were treated with intravenous paclitaxel 50-110 mg/m(2) (Day 1), oral topotecan 0.5-2.0 mg/m(2) (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/m(2), topotecan 1.5 mg/m(2), and etoposide 160 mg/m(2) without G-CSF. In minimally pretreated patients, G-CSF allowed paclitaxel dose escalation to 110 mg/m(2). 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/m(2), topotecan 1.5 mg/m(2), and etoposide 160 mg/m(2) with G-CSF support in minimally pretreated patients.

Authors+Show Affiliations

Department of Medicine, University of Miami Sylvester Cancer Center, Miami, Florida 33136, USA. crocha@med.miami.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15197811

Citation

Rocha Lima, Caio M S., et al. "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, 2004, pp. 2671-9.
Rocha Lima CM, Catapano CV, Pacheco D, et al. 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. 2004;100(12):2671-9.
Rocha Lima, C. M., Catapano, C. V., Pacheco, D., Sherman, C. A., Oakhill, G., Mushtaq, C., Freeman, K. D., & 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), 2671-9.
Rocha Lima CM, et al. 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. 2004 Jun 15;100(12):2671-9. PubMed PMID: 15197811.
* Article titles in AMA citation format should be in sentence-case
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 - 2004/6/16/pubmed PY - 2004/6/24/medline PY - 2004/6/16/entrez SP - 2671 EP - 9 JF - Cancer JO - Cancer VL - 100 IS - 12 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 < or = 2 were treated with intravenous paclitaxel 50-110 mg/m(2) (Day 1), oral topotecan 0.5-2.0 mg/m(2) (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/m(2), topotecan 1.5 mg/m(2), and etoposide 160 mg/m(2) without G-CSF. In minimally pretreated patients, G-CSF allowed paclitaxel dose escalation to 110 mg/m(2). 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/m(2), topotecan 1.5 mg/m(2), and etoposide 160 mg/m(2) with G-CSF support in minimally pretreated patients. SN - 0008-543X UR - https://www.unboundmedicine.com/medline/citation/15197811/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_ L2 - https://doi.org/10.1002/cncr.20330 DB - PRIME DP - Unbound Medicine ER -