The combined use of radiation therapy and lonidamine in the treatment of brain metastases

DeAngelis, Lisa M.; Currie, Violante E.; Kim, Jae-Ho; Krol, George; O'Hehir, M; Farag, Fouad; Young, Charles W.; Posner, Jerome B.

doi:10.1007/bf00172917

Cited by 72 publications

(33 citation statements)

References 18 publications

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“…Thus the present study does not confirm the suggestion of Besner et al (1984) that the trough level of Lonidamine is lower (< 3 1tg ml-') in unresponsive patients than in responding individuals. In agreement with the present results, De Angelis et al (1989) failed to detect any difference in Lonidamine plasma levels in patients with brain metastases who did or did not respond to the drug when given with radiotherapy.…”

Section: Discussionsupporting

confidence: 92%

A phase II clinical and pharmacokinetic study of Lonidamine in patients with advanced breast cancer

Mansi

A²,

Dr³

et al. 1991

Br J Cancer

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Summary Lonidamine is a substituted indazole carboxylic acid with a unique mechanism of action and early clinical studies have reported anti-tumour activity.In a phase II study 32 patients with previously treated advanced breast cancer were given Lonidamine in a daily divided oral dose of 600 mg. Of 28 patients evaluable for response, three (11%) achieved a partial response (4-24 + months) and three (11%) a minor response. Two patients have stable disease (> 3 months) and 20 progressed. Toxicity was very mild. Sixteen (53%) of 31 patients had myalgia which lasted a median of 2 weeks. This was investigated with nuclear magnetic resonance spectroscopy in four patients but the changes were unrelated to the degree of myalgia. No other major side-effect was seen, and no dose reduction was required.Lonidamine pharmacokinetics have been investigated in 17 patients 1 month after the start of therapy. Lonidamine was detected in the plasma of all patients, but there was no clear relationship between Lonidamine levels and clinical response or toxicity.Lonidamine appears to be active against advanced breast cancer and its low toxicity would allow combination studies with chemotherapy.

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Section: Discussionsupporting

confidence: 92%

A phase II clinical and pharmacokinetic study of Lonidamine in patients with advanced breast cancer

Mansi

A²,

Dr³

et al. 1991

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%

“…Patients with a solitary brain metastasis, good performance status, and controlled extracranial disease may be considered for more aggressive treatment such as surgery with postoperative radiotherapy or stereotactic radiosurgery. Radiosensitizers, chemotherapy, and various radiotherapy dose fractionation schedules have also been explored to improve the outcome of brain metastases [7][8][9][10][11] .…”

Section: Introductionmentioning

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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“…The following radiosensitizers have been studied in randomized controlled trials: motexafin gadolinium, 22 RSR13 (efaproxiral), 23 celecoxib, 24 paclitaxel, 25 lonidamine, 26 metronidazole, 27 misonidazole, 28 and bromodeoxyuridine. 29 In a phase III trial, motexafin gadolinium (MGd) improved time to neurologic progression in all patients (median, 4.3 months for MGd vs 3.8 months for WBRT; p ϭ 0.018); in lung cancer patients, the time to neurologic progression was longer (median, 5.5 months for MGd vs 3.7 months for WBRT; p ϭ 0.025).…”

Section: Whole-brain Radiation Therapymentioning

confidence: 99%

Current Management of Metastatic Brain Disease

Ranjan

Abrey

2009

Neurotherapeutics

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Summary: Brain metastases are the most common intracranial tumor in adults. The incidence of metastases is thought to be rising due to better detection and treatment of systemic malignancy. More widespread use and improved quality of MRI may lead to early detection of brain metastases. Available evidence suggests that survival is longer and quality of life improved if brain metastases are treated aggressively. This article reviews current therapeutic management used for brain metastases. To select the appropriate therapy, the physician must consider the extent of the systemic disease, primary histology, and patient age and performance status, as well as the number, size, and location of the brain metastases. Available treatment options include whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), surgery, and chemotherapy. Multidisciplinary approaches such as the combination of WBRT with SRS or surgery have shown superior results in terms of survival time, neurocognitive function, and quality of life. The utility and optimal use of chemotherapy and radiosensitizing agents is less clear. It is hoped that further advances and multidisciplinary approaches currently under study will result in improved patient outcomes. Key Words: Brain metastases, brain metastasis chemotherapy, brain metastasis radiotherapy, metastatic brain tumor, brain neoplasm.

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The combined use of radiation therapy and lonidamine in the treatment of brain metastases

Cited by 72 publications

References 18 publications

A phase II clinical and pharmacokinetic study of Lonidamine in patients with advanced breast cancer

A phase II clinical and pharmacokinetic study of Lonidamine in patients with advanced breast cancer

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

Current Management of Metastatic Brain Disease

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