Phase I/II Trial of Simultaneous Whole-Brain Irradiation and Dose-Escalating Topotecan for Brain Metastases

Köcher, Martin; Eich, Hans-Theodor; Semrau, R.; Güner, S.A.; Müller, Rolf-Peter

doi:10.1007/s00066-005-1242-9

Cited by 30 publications

(18 citation statements)

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“…Compared with our own previous data generated in a phase I/II study, where we found overall response rates of 72% (Hedde et al, 2007), the outcome of the patients treated with a combined approach was inferior. However, our results confirm the findings of the only two comparable studies testing a topotecan-based radiochemotherapy, in which overall response rates of 46 and 58%, respectively, were described (Gruschow et al, 2002;Kocher et al, 2005).…”

Section: Discussionsupporting

confidence: 90%

“…As a consequence, three phase I/II-studies were initiated to evaluate the feasibility of topotecan-based combined radiochemotherapy in patients with brain metastases (Gruschow et al, 2002;Kocher et al, 2005;Hedde et al, 2007). In the setting of the doseescalating phase I studies, Gruschow et al (2002) and Hedde et al (2007) found tolerable toxicities in those patients receiving 0.4 mg m À2 day À1 topotecan, either as a bolus or continuous infusion, concurrent with the WBRT (fraction size of 2 Gy day À1 for a total of 40 Gy).…”

mentioning

confidence: 99%

“…In the setting of the doseescalating phase I studies, Gruschow et al (2002) and Hedde et al (2007) found tolerable toxicities in those patients receiving 0.4 mg m À2 day À1 topotecan, either as a bolus or continuous infusion, concurrent with the WBRT (fraction size of 2 Gy day À1 for a total of 40 Gy). Kocher et al (2005) used a regimen with local target dosage of 36 Gy in 3-Gy-fractions and topotecan administered 12 Â 0.5 mg m À2 day À1 . In the study published by Hedde et al (2007) 19% of their 68 patients developed grade 3/4 haematological and 21% developed grade 3/4 non-haematological events.…”

mentioning

confidence: 99%

“…Of the 47 patients who took part in the study of Kocher et al (2005), response evaluation was possible in 26 patients. In them, an overall response rate of 58% was described (5 out of 26 complete response (CR) and 10 out of 26 partial response (PR)).…”

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confidence: 99%

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A phase III trial of topotecan and whole brain radiation therapy for patients with CNS-metastases due to lung cancer

Neuhaus

Müller³

et al. 2009

Br J Cancer

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Brain metastases represent an important cause of morbidity in patients with lung cancer and are associated with a mean survival of less than 6 months. Thus, new regimens improving the outcome of these patients are urgently needed. On the basis of promising data raised in a phase I/II trial, we initiated an open, randomised, prospective, multicentric phase III trial, comparing whole brain radiation therapy (WBRT; 20 Â 2 Gy) alone with WBRT þ topotecan (RCT; 0.4 mg m À2 day À1 Â 20). A total of 320 patients with CNSmetastases due to SCLC or NSCLC were projected. The primary end point was overall survival, whereas second end points were local response and progression-free survival. However, until the cutoff date of study completion (i.e., a study duration of 34 months), only a total of 96 (RCT:47, WBRT:49) patients had been recruited, and so an analysis was performed at that time point. Although the numbers of grade 3/4 non-haematological toxicities (besides alopecia 115 (RCT/WBRT: 55 out of 60) were evenly distributed, the 25 haematological events occurred mainly in the combined treatment arm (24 out of 1). Local response, evaluated 2 weeks after treatment, was assessable in 44 (RCT/WBRT: 23 out of 21) patients, showing CR in eight (3 out of 5), PR in 17 (11 out of 6), SD in 14 (8 out of 6) and PD in five (1 out of 4) patients (all differences n.s.). Neither OAS (RCT/WBRT: median (days)): 87 out of 95, range 3 -752/4 -433; HR 1.32; 95% CI (0.83; 2.10)) nor PFS (median (days)): 71 out of 66, range, 3 -399/4 -228; HR 1.28, 95% CI (0.73; 2.43) differed significantly. On the basis of these results and the slow recruitment, a continuation of the study did not seem reasonable. The available data show no significant advantage for concurrent radiochemotherapy for patients with lung cancer; however, the recruited number of patients is too low to exhibit a small advantage of combined treatment.

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Section: Discussionsupporting

confidence: 90%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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A phase III trial of topotecan and whole brain radiation therapy for patients with CNS-metastases due to lung cancer

Neuhaus

Müller³

et al. 2009

Br J Cancer

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“…Two retrospective trials examined the outcomes of multiple treatments including WBRT, surgery, chemotherapy, or supportive care 42,43 . Twelve studies examined the use of various WBRT dose fractionation schedules 6,10,22,28,[44][45][46][47][48][49][50][51] , and seven trials assessed the efficacy of radiosensitizers and WBRT as compared with WBRT alone 9,21,24,25,[52][53][54] . Chemotherapy and WBRT were compared in eight studies 7,8,[55][56][57][58][59][60] .…”

Section: Multiple Brain Metastasesmentioning

confidence: 99%

Quality of Life in Brain Metastases Radiation Trials: A Literature Review

et al. 2008

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BackgroundAn estimated 20%-40% of cancer patients will develop brain metastases. Whole-brain radiotherapy (WBRT) is the standard treatment for patients with brain metastases. Although WBRT can reduce neurologic symptoms, the median survival following WBRT is between 3 and 6 months. Given this limited survival, it is important to consider quality of life (QOL) when treating patients with brain metastases. However, few studies have focused on QOL and improvement in patient-rated symptoms as primary outcomes. ObjectiveFor an accurate measurement of the extent to which previous trials have utilized QOL tools to evaluate the efficacy of WBRT for treatment of brain metastases, we undertook a literature review to examine the common endpoints and QOL instruments used. MethodsWe conducted a systematic search using the MEDLINE (1950( to December 2007 and Cochrane Central Register of Controlled Trials (4th quarter 2007) databases. Eligible studies investigated WBRT in one of the study arms. The following outcomes were included: median survival, overall survival, neurologic function, 1-year local control, and overall response; use of QOL instruments, performance status scales, and neurologic function assessments; and use of other assessment tools. Patient-rated QOL instruments were defined as those that strove to assess all dimensions of QOL; observerrated performance instruments such as the Karnofsky performance status (KPS) were deemed to be performance scales. ResultsWe identified sixty-one trials that included WBRT nine evaluated the treatment of a single brain metastasis, and fifty-two evaluated the treatment of multiple brain metastases. Although fifty-five of the trials employed a QOL instrument, few trials focused on QOL as an outcome. We found 23 different instruments used to evaluate QOL. The most commonly employed instrument was the KPS (n = 33), followed by various neurologic function classification scales (n = 21). A preponderance of the studies used 1 (n = 26, 43%) or 2 (n = 21, 34%) QOL instruments.A total of fourteen published trials on brain metastases included an evaluation of the study population's QOL. Those trials included three that used the Functional Assessment of Cancer Therapy-General scale and Brain subscale instrument, three that used the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (C30) and the Brain Cancer Module 20 instrument, two that used study-designed QOL instruments, one that used the Edmonton Symptom Assessment Scale, two that used the Spitzer Quality of Life index, and three that used the KPS to evaluate QOL. Some trials reported deterioration in QOL after WBRT in patients with poorer prognosis; other trials detected an improvement in QOL after WBRT in patients with better prognosis. ConclusionsTo date, fourteen trials in brain metastases that have included an evaluation of the study population's QOL have been published. Although some studies showed that certain parameters of QOL deteriorate after WBRT, other studies showed that Q...

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Applications in Malignant Brain Tumors

Nieder

Gilbert

Multimodal Concepts for Integration of Cytotoxic Drugs

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Phase I/II Trial of Simultaneous Whole-Brain Irradiation and Dose-Escalating Topotecan for Brain Metastases

Cited by 30 publications

References 31 publications

A phase III trial of topotecan and whole brain radiation therapy for patients with CNS-metastases due to lung cancer

A phase III trial of topotecan and whole brain radiation therapy for patients with CNS-metastases due to lung cancer

Quality of Life in Brain Metastases Radiation Trials: A Literature Review

Applications in Malignant Brain Tumors

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