Phase I clinical and pharmacokinetic study of topotecan administered by a 24-hour continuous infusion.

Warmerdam, L. J. C. van; Huinink, W.W. ten Bokkel; Rodenhuis, S.; Koier, I.; Davies, Brian E.; Rosing, Hilde; Maes, R. A. A.; Beijnen, Jos H.

doi:10.1200/jco.1995.13.7.1768

Cited by 61 publications

(26 citation statements)

References 15 publications

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“…Wall et al 29 and van Warmerdam et al 30 proposed an administration on day 1 respectively by a 30 min infusion or a 24 h CI. As a 30 min infusion and at a dose of 22.5 mg/m 2 , dose-limiting toxicity was the myelosuppression.…”

Section: Discussionmentioning

confidence: 99%

“…As a 24 h CI given every 28 days and at a dose of 10.5 mg/m 2 /day, the toxicity was primarily haematological, with grade III-IV neutropenia occurring in 30% of the patients and grade IV thrombocytopenia in 44% of the patients. 30 Two other studies have explored an administration of HD topotecan for 5 days by a continuous 24 h infusion. In the Kantarjian et al's 31 trial, the dose level tested ranged from 3.5 to 18 mg/m 2 .…”

Section: Discussionmentioning

confidence: 99%

“…30 With a continuous 5-day infusion, the MTD was set up at 10.5 mg/m 2 . 31,32 Without and with AHSCT and G-CSF support, MTDs were respectively 10 and 17.5 mg/m 2 .…”

Section: Discussionmentioning

confidence: 99%

“…These regimens could merit further studies in various solid and haematologic tumours. [33][34][35] 30 CI (24 h) Myelosuppression 10.5 mg/m 2 /day Â 1 day 10.5 Kantarjian (1993) 31 CI (120 h) Severe mucositis, gastrointestinal bleeding 2.0 mg/m 2 /day Â 5 days 10 Rowinsky (1994) 32 CI (120 h) Gastroenteritis mucositis of perianal tissues 2.1 mg/m 2 /day Â 5 days 10.5 Rowinsky (1996) 28 30 min, 5 days+G-CSF Myelosuppression, cutaneous toxicity 3.5 mg/m 2 /day Â 5 days 17.5…”

Section: Discussionmentioning

confidence: 99%

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Phase I study of high-dose topotecan with haematopoietic stem cell support in the treatment of ovarian carcinomas: the ITOV 01 protocol

Lotz

Pautier

Selle

et al. 2006

Bone Marrow Transplant

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Topotecan has demonstrated activity in ovarian carcinomas. In order to increase the tumour response rate and to define the maximum tolerated dose (MTD) of topotecan, we decided to develop a high-dose phase I regimen supported by stem cell support. High-doses schedules using a 1-day single administration have MTDs of 10.5 (24 h continuous infusion (CI)) or 22.5 mg/m 2 (30 min infusion). Five-day CI induces grade IV mucositis at high doses (MTDo12 mg/m 2 ). We chose to administer topotecan in a 5-day schedule with a 30 min daily infusion. Patients were scheduled to receive one cycle of therapy. The first dose level was 4.0 mg/m 2 /day Â 5 days. Limiting toxicities were defined as toxic death, grade IV nonhaematopoietic or haematopoietic toxicity 46 weeks. From August 1998 to April 2002, 49 patients were included. Forty-three patients have completed one course and 15 have received two cycles. One patient treated at level 7 mg/m 2 /day died of sepsis. Median duration of grade IV neutropenia was 9 days. Two episodes of grade IV diarrhoea were observed at level 9.5 mg/m 2 /day. Pharmacokinetic data were linear within the dose range of 4-9.0 mg/m 2 /day. The MTD was reached at 9 mg/m 2 / day Â 5 days.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…30 With a continuous 5-day infusion, the MTD was set up at 10.5 mg/m 2 . 31,32 Without and with AHSCT and G-CSF support, MTDs were respectively 10 and 17.5 mg/m 2 .…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Phase I study of high-dose topotecan with haematopoietic stem cell support in the treatment of ovarian carcinomas: the ITOV 01 protocol

Lotz

Pautier

Selle

et al. 2006

Bone Marrow Transplant

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“…Phase I and II clinical trials have been performed to evaluate the administration of topotecan by continuous i.v. infusion for periods of 24 h (van Warmerdam et al, 1995;Abbruzzese et al, 1996;Hoskins et al, 1998), 72 h (Burris et al, 1994), 120 h (Burris et al, 1994) and 21 days (Hochster et al, 1994). The Canadian National Cancer Institute conducted a randomised phase II trial to investigate the schedule dependence of topotecan (Hoskins et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

A phase I clinical trial of continual alternating etoposide and topotecan in refractory solid tumours

et al. 2005

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The goal of this phase I study was to develop a novel schedule using oral etoposide and infusional topotecan as a continually alternating schedule with potentially optimal reciprocal induction of the nontarget topoisomerase. The initial etoposide dose was 15 mg m À2 b.i.d. days (D)1 -5 weeks 1,3,5,7,9 and 11, escalated 5 mg per dose per dose level (DL). Topotecan in weeks 2,4,6,8,10 and 12 was administered by 96 h infusion at an initial dose of 0.2 mg m À2 day À1 with a dose escalation of 0.1, then at 0.05 mg m À2 day À1 . Eligibility criteria required no organ dysfunction. Two dose reductions or delays were allowed. A total of 36 patients with a median age of 57 (22 -78) years, received a median 8 (2 -19) weeks of chemotherapy. At DL 6, dose-limiting toxicities consisted of grade 3 nausea, vomiting and intolerable fatigue. Three patients developed a line-related thrombosis or infection and one subsequently developed AML. There was no febrile neutropenia. There were six radiologically confirmed responses (18%) and 56% of patients demonstrated a response or stable disease, typically with only modest toxicity. Oral etoposide 35 mg m À2 b.i.d. D1 -5 and 1.8 mg m À2 96 h (total dose) infusional topotecan D8 -11 can be administered on an alternating continual weekly schedule for at least 12 weeks, with promising clinical activity.

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Phase II evaluation of topotecan for pediatric central nervous system tumors

Blaney

Phillips

Packer

et al. 1996

Cancer

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Phase I clinical and pharmacokinetic study of topotecan administered by a 24-hour continuous infusion.

Abstract: The recommended dose for phase II studies is 8.4 mg/m2 when administered as a 24-hour infusion, which is well tolerated. Further studies will be necessary to account for the putative nonlinear behavior of the drug.

Cited by 61 publications

References 15 publications

Phase I study of high-dose topotecan with haematopoietic stem cell support in the treatment of ovarian carcinomas: the ITOV 01 protocol

Phase I study of high-dose topotecan with haematopoietic stem cell support in the treatment of ovarian carcinomas: the ITOV 01 protocol

A phase I clinical trial of continual alternating etoposide and topotecan in refractory solid tumours

Phase II evaluation of topotecan for pediatric central nervous system tumors

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