A phase I/II trial of topotecan and radiation therapy for brain metastases in patients with solid tumors.
OBJECTIVE
Outcomes in patients with brain metastases undergoing whole-brain radiotherapy (WBRT) are hardly encouraging, and an improvement in results is therefore needed. One possible approach is the addition of chemotherapeutics. However the data presented thus far are also disappointing. A promising substance in this setting could become topotecan, which is known to cross the blood-brain barrier and additionally offers radiosensitizing effects. Therefore we performed a phase I/II trial to evaluate the feasibility of a concurrent radiochemotherapy regimen.


METHODS
From January 1999 to July 2001, a total of 75 patients (10 in phase I and 65 in phase II) were included. The WBRT was applied with a fraction size of 2 Gy/day for a total of 40 Gy. Topotecan was administered as a 30-min infusion with 0.2 to 0.5 mg/m(2)/day for 5 days over 4 weeks within 2 h to radiation therapy.


RESULTS
Because of the higher toxic rates seen in patients receiving 0.5 mg/m(2)/day, the recommended dosage for phase II was 0.4 mg/m(2)/day. In this group Grade 3/4 hematologic and nonhematologic side effects occurred in 19% and 21% of the patients, respectively. The overall response rate was 72% with an overall survival of 17 weeks and 30 weeks among the responders.


CONCLUSIONS
Based on the moderate toxicity profile presented here we recommend to perform a phase III trial to confirm the promising phase I/II data.
Hedde
Jan-Peter
JP
Radiological Department, City Hospital of Merheim, Cologne, Germany.
Neuhaus
Thomas
T
Schüller
Heinrich
H
Metzler
Ute
U
Schmidt-Wolf
Ingo G H
IG
Kleinschmidt
Rolf
R
Losem
Christoph
C
Lange
Oliver
O
Grohe
Christian
C
Stier
Sebastian
S
Ko
Yon-Dschun
YD
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000556:secondary* / Q000628:therapy*; D001943:Breast Neoplasms / Q000628:therapy*; D004307:Dose-Response Relationship, Radiation; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant / Q000379:methods*; D019772:Topotecan / Q000008:administration & dosage*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D019772:Topotecan