Acute toxicity and changes in quality of life during a combined radio-chemotherapy of glioblastomas with topotecan (Hycamtin).
BACKGROUND
Because of the pronounced radioresistance of glioblastoma multiforme the prognosis of this disease remains poor. Therefore, we investigated the impact of an additional simultaneous chemotherapy with the topoisomerase-I inhibitor topotecan (Hycamtin) on the quality of life and toxicity of radiotherapy.


METHODS
In this multicenter trial patients with histologically proven glioblastoma multiforme underwent a simultaneous radio-chemotherapy. Including pilot phase 60 patients, 41 male and 19 female, were treated. Age ranged from 26 to 76 years, the mean was 57 years. Conventional fractionated conformal radiotherapy was performed with daily doses of 2.0 Gy to a total dose of 60 Gy. 1 hour prior to irradiation 0.5 mg (absolute dose) of topotecan were administered intravenously resulting in a cumulative dose of 15 mg. Besides hematologic and non-hematologic toxicity, quality of life was assessed by Karnofsky index and Spitzer index. Additionally local control and survival time were recorded.


RESULTS
57 patients completed the combined therapy. Median administered dose of radiation was 60 Gy (16-76 Gy). Median cumulative topotecan dose was 15 mg (7.5-18.5 mg). Grade-III toxicity was found in six cases (two hematologic, two motoric disorder, one infection, one nausea) and grade-IV toxicity in three cases (one esophagitis, one motoric disorder, one mental disorder). Two patients died of septic disease most likely caused by steroid induced immunosuppression. Mean Karnofsky index and Spitzer index initially, at the end of therapy and 6 weeks after therapy showed values of 87%, 81% and 80% and 19 points, 18 points and 19 points, respectively. Median survival time was 15 months.


CONCLUSIONS
This multimodal approach for patients with glioblastoma multiforme is well tolerated. Quality of life remains preserved and outpatient treatment is possible. The relatively long median survival time even for patients bearing macroscopic tumors is promising.
Gross
M W
MW
Department of Radiotherapy and Radiooncology, Philipps-University of Marburg, Germany. gross@mailer.uni-marburg.de
Altscher
R
R
Brandtner
M
M
Häusser-Mischlich
H
H
Kiricuta
I C
IC
Siegmann
A D
AD
Engenhart-Cabillic
R
R
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D003627:Data Interpretation, Statistical; D019583:Dose Fractionation, Radiation; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D017567:Karnofsky Performance Status; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011788:Quality of Life; D011878:Radiotherapy / Q000009:adverse effects; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal; D016019:Survival Analysis; D013997:Time Factors; D059004:Topoisomerase I Inhibitors; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D059004:Topoisomerase I Inhibitors; D019772:Topotecan