Platinum Concentrations in Human Autopsy Tumor Samples

Stewart, David J.; Mikhael, Nadia Z.; Nair, Rama C.; Kacew, Sam; Montpetit, V.; Nanji, Amin A.; Maroun, J.; Howard, Katherine M.

doi:10.1097/00000421-198804000-00013

Cited by 67 publications

(26 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although most cytotoxic agents do not cross the blood-brain barrier under normal conditions, there is evidence that the blood-tumor barrier is far more permissive (71,72). Therefore, it is likely that responses in the CNS are influenced by similar considerations as systemic response, such as prior therapy and the biological characteristics of the tumor.…”

Section: New Directionsmentioning

confidence: 99%

Brain Metastases: The HER2 Paradigm

Lin

Winer²

2007

Clinical Cancer Research

374

278

View full text Add to dashboard Cite

Between 100,000 and 170,000 patients with cancer develop central nervous system (CNS) metastases each year in the U.S., of which f20% carry a primary diagnosis of breast cancer. As a consequence of improvements in systemic therapy, which have allowed patients to live longer with advanced cancer, CNS metastases are emerging as an important sanctuary site, and the incidence may be increasing in patients with particular tumor subtypes. Unless there are improvements in the treatment of CNS disease, a growing proportion of patients may be at risk of experiencing both morbidity and mortality as a result of uncontrolled CNS progression, often at a time when their extra-CNS disease is apparently under control. This article reviews changes in the epidemiology and natural history of women with brain metastases from HER2-positive breast cancer over the last decade and presents the therapeutic challenges and opportunities that have arisen in this setting. First, the apparent increase in CNS disease among women with HER2-positive breast cancer, relative to historical controls, is discussed, followed by consideration of potential causes of this observation. Next, the implications of CNS disease, in terms of prognosis and the potential development of preventive strategies are considered. Finally, new developments in systemic approaches to the treatment of CNS disease, including cytotoxic chemotherapy and targeted therapy, are explored.

show abstract

Section: New Directionsmentioning

confidence: 99%

Brain Metastases: The HER2 Paradigm

Lin

Winer²

2007

Clinical Cancer Research

374

278

View full text Add to dashboard Cite

show abstract

“…14,15 Although neither gefitinib nor lapatinib cross the intact blood-brain barrier to a significant degree in pre-clinical models, the blood-tumor barrier may be more permissive, leading to the hypothesis that lapatinib may have activity in established CNS disease. 16,17 We conducted a phase II study to evaluate the clinical efficacy and adverse-effect profile of lapatinib in the treatment of women with brain metastases from HER-2-positive breast cancer. On the basis of the activity of lapatinib in refractory breast cancer, and its structural similarity to gefitinib, we hypothesized that lapatinib would be active in women with HER-2-positive breast cancer metastatic to the brain.…”

Section: Introductionmentioning

confidence: 99%

Phase II Trial of Lapatinib for Brain Metastases in Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

Lin

Carey

Liu

et al. 2008

JCO

431

251

View full text Add to dashboard Cite

Purpose-One third of women with advanced human epidermal growth factor receptor 2 (HER-2)-positive breast cancer develop brain metastases; a subset progress in the CNS despite standard approaches. Medical therapies for refractory brain metastases are neither well-studied nor Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTAlthough all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Author Manuscript Author ManuscriptAuthor Manuscript Author Manuscript established. We evaluated the safety and efficacy of lapatinib, an oral inhibitor of epidermal growth factor receptor (EGFR) and HER-2, in patients with HER-2-positive brain metastases. Results-Thirty-nine patients were enrolled. All patients had developed brain metastases while receiving trastuzumab; 37 had progressed after prior radiation. One patient achieved a PR in the brain by RECIST (objective response rate 2.6%, 95% conditional CI, 0.21% to 26%). Seven patients (18%) were progression free in both CNS and non-CNS sites at 16 weeks. Exploratory analyses identified additional patients with some degree of volumetric reduction in brain tumor burden. The most common adverse events (AEs) were diarrhea (grade 3, 21%) and fatigue (grade 3, 15%). Patients and Methods-Patients Conclusion-The study did not meet the predefined criteria for antitumor activity in highly refractory patients with HER-2-positive brain metastases. Because of the volumetric changes observed in our exploratory analysis, further studies are underway utilizing volumetric changes as a primary end point.

show abstract

“…CDDP is not known to cross the intact blood-brain-barrier, and it is not found in significant concentrations in the brain and CSF of animal and humans after systemic administration [14]. In cases likely to have an abnormal blood-brain barrier, autopsy studies have demonstrated a detectable concentration of platinum in glioblastoma tissue of patient treated with CDDP up to eight months before tissue analysis [15,16]. Historically, intra-arterial CDDP has been tested alone or in combination with other drugs for the treatment of primary or recurrent gliomas.…”

Section: Discussionmentioning

confidence: 99%

Intra-arterial cisplatin in malignant brain tumors: incidence and severity of otic toxicity

Assietti

Olson

1996

J Neuro-Oncol

View full text Add to dashboard Cite

Intra-arterial (IA) cisplatin is used to treat gliomas with the goal of maximizing drug concentration in the brain while minimizing systemic toxicity. The present study is based on the author's experience with IA cisplatin administration in 12 patients. The primary goal of the study was to document the extent of otic toxicity in these individuals. Hearing was tested clinically and with audiograms, before each IA cisplatin injection. Eight women and four men with a mean age of 39 1/2 years (range 22-61) were treated. Diagnoses included 7 glioblastoma multiformes, 4 anaplastic astrocytomas, and 1 gliosarcoma. Diagnosis was obtained by stereotactic biopsy in four and craniotomy for resection and debulking in eight. The mean number of IA injections per patient was 4.58 (range 3-6). The cisplatin dose was 60 mg/m2 with the average dose of cisplatin per cycle being 116 mg (range 96-130 mg). Eleven patients had the agent administered via the internal carotid and one received it by way of a vertebral artery. Nine of the twelve patients (75%) demonstrated pure tone loss, as measured by audiography, of greater than 15 dB in the higher frequencies range (> or = 3 kHz) bilaterally. One patient became deaf and two others had clinically significant hearing loss. The severity of the auditory damage increased after each administration in each of the cases with clinical abnormality. IA cisplatin may have a role in the treatment of patients with primary malignant brain tumors, but further developments to limit otic toxicity would be of value.

show abstract

Platinum Concentrations in Human Autopsy Tumor Samples

Cited by 67 publications

References 0 publications

Brain Metastases: The HER2 Paradigm

Brain Metastases: The HER2 Paradigm

Phase II Trial of Lapatinib for Brain Metastases in Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

Intra-arterial cisplatin in malignant brain tumors: incidence and severity of otic toxicity

Contact Info

Product

Resources

About