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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
Article first published online: 14 MAY 2004
Copyright © 2004 American Cancer Society
Volume 100, Issue 12, pages 2671–2679, 15 June 2004
How to Cite
Rocha Lima, C. M. S., Catapano, C. V., Pacheco, D., Sherman, C. A., Oakhill, G., Mushtaq, C., Freeman, K. D. and 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: 2671–2679. doi: 10.1002/cncr.20330
- Issue published online: 2 JUN 2004
- Article first published online: 14 MAY 2004
- Manuscript Accepted: 31 MAR 2004
- Manuscript Revised: 26 MAR 2004
- Manuscript Received: 22 OCT 2003
- combination chemotherapy;
- lung carcinoma;
- Phase I trial
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.
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/m2 (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.
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%).
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/m2, and etoposide 160 mg/m2 with G-CSF support in minimally pretreated patients. Cancer 2004. © 2004 American Cancer Society.