Treatment > Topotecan

Abstract

A phase I/II trial of topotecan and radiation therapy for CNS-metastases of patients with solid tumors

J.-P. Hedde, Y. Ko, U. Metzler, H. Vetter, I. G. Schmidt-Wolff, C. Grohe, O. Lange, S. Kaubitzsch, H. Schueller

Staedtisches Krankenhaus Koeln-Merheim, Koeln, Germany; University, Bonn, Germany; GlaxoSmithKline, Munich, Germany

Brain metastases are common during the course of lung or breast cancer.
The objective of our phase I/II study was to define the optimal dose of a topotecan treatment given simultaneously with whole brain radiotherapy (WBRT: 20 fractions with 2 Gy) and to assess the efficacy in patients with lung or breast cancer and cerebral relapse after initial therapy.
Eighty patients (pts) were eligible: 45 NSCLC, 27 SCLC, and 8 breast cancer; ECOG 0-1 (1 pt ECOG 3); number of brain metastases was 1 (10 pts), 2-3 (31 pts), >4 (29 pts) or not reported (10 pts).
Dose escalation was performed in a phase I design with a starting dose of 0.2 mg/m2 x 20 to 0.5 mg/m2 x 20, reaching the dose-limiting toxicity (mainly thrombocytopenia).
Consequently, the phase II study was performed with topotecan 0.4 mg/m2 x 20.
Treatment was completed in 57 pts.
Grade 3/4 hematological toxicity was seen in 19 pts (anemia 1/0, leucopenia 8/3, thrombocytopenia 4/3).
Non-hematological toxicity Grade 3/4 was reported for 23 pts (constipation 3/0, stomatitis 2/0, infection 6/4, neuropathy 6/0, dizziness 1/0 and fatigue 2/0).
Infection occurred only at the beginning of the study if dexamethasone was given at dosages >12 mg daily.
Of 52 patients available for reassessment, extracerebral response was reported for 37 (72%): 4 CR (2 NSCLC, 2 SCLC) 2 PR (1 NSCLC, 1 SCLC), 10 SD (9 NSCLC, 1 SCLC) and 21 PD.
16 pts died prior to assessment and 12 pts could not be assessed due to their poor condition.
Overall mean survival was 25.3 + 5.5 weeks; 33.5 weeks in the CR + PR group; 26.7 weeks in the SD + PD group; and, in patients not assessed, 12.4 weeks.
Adding topotecan to WBRT results in a tolerable regimen with high response rates of brain metastases.
Patients with good performance status (ECOG 0 or 1) appear to have a higher response to treatment and patients with response have a survival benefit.

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