Interstitial Chemotherapy with Carmustine-loaded Polymers for High-grade Gliomas: A Randomized Double-blind Study

Valtonen, S.; Timonen, Ulla; Toivanen, Petri; Kalimo, Hannu; Kivipelto, Leena; Heiskanen, O; Unsgaard, Geirmund; Kuurne, T

doi:10.1097/00006123-199707000-00011

Cited by 379 publications

(228 citation statements)

References 11 publications

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“…With respect to additional data on the benefit of local chemotherapy, 2 previous placebo-controlled, doubleblind studies of BCNU wafers in malignant glioma have been conducted (Brem et al, 1995;Valtonen et al, 1997). In all 3 studies, BCNU wafers have shown a survival benefit compared to placebo wafers, with a mortality risk reduction of 31% (Brem et al in recurrent malignant glioma), 63% (Valtonen et al in primary malignant glioma), and 29% (the present study).…”

Section: Discussionmentioning

confidence: 59%

“…In an initial small study of patients (N = 32) with primary malignant glioma, BCNU wafer-treated patients (n = 16) had a median survival of 13.4 months vs. 9.2 months for the placebo wafer-treated patients (n = 16). The BCNU wafer-treated patients had significantly improved 12-month and overall survival compared to placebo wafer-treated patients (Valtonen et al, 1997).…”

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confidence: 86%

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A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma

Westphal

Hilt²,

Bortey³

et al. 2003

Neuro-Oncology

1,074

357

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A previous placebo-controlled trial has shown that biodegradable 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers (Gliadel wafers) prolong survival in patients with recurrent glioblastoma multiforme. A previously completed phase 3 trial, also placebo controlled, in 32 patients with newly diagnosed malignant glioma also demonstrated a survival benefit in those patients treated with BCNU wafers. Because of the small number of patients in that trial, a larger phase 3 trial was performed to confirm these results. Two hundred forty patients were randomized to receive either BCNU or placebo wafers at the time of primary surgical resection; both groups were treated with external beam radiation postoperatively. The two groups were similar for age, sex, Karnofsky performance status (KPS), and tumor histology. Median survival in the intentto-treat group was 13.9 months for the BCNU wafertreated group and 11.6 months for the placebo-treated group (log-rank P-value stratified by country = 0.03), with a 29% reduction in the risk of death in the treatment group. When adjusted for factors affecting survival, the treatment effect remained positive with a risk reduction of 28% (P = 0.03). Time to decline in KPS and in 10/11 neuroperformance measures was statistically significantly prolonged in the BCNU wafer-treated group (P ≤ 0.05). Adverse events were comparable for the 2 groups, except for CSF leak (5% in the BCNU wafer-treated group vs. 0.8% in the placebo-treated group) and intracranial hypertension (9.1% in the BCNU wafer-treated group vs. 1.7% in the placebo group). This study confirms that local chemotherapy with BCNU wafers is well tolerated and offers a survival benefit to patients with newly diagnosed malignant glioma. Neuro-Oncology 5, 79-88, 2003 (Posted to Neuro-Oncology [serial online], Doc. 02-023, February 10, 2003 P resently, malignant gliomas are treated by resection, external beam radiation, and, in some cases, systemic chemotherapy (Cairncross et al

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Section: Discussionmentioning

confidence: 59%

mentioning

confidence: 86%

A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma

Westphal

Hilt²,

Bortey³

et al. 2003

Neuro-Oncology

1,074

357

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“…Biodegradable controlled-release polymers loaded with carmustine have been established as a safe and effective therapy for patients with malignant gliomas (8)(9)(10)(11)(12). Given the inherent advantages of locally-delivered chemotherapy, there has been continued interest in the development of additional controlled-release drug delivery systems suitable for intraparenchymal administration of novel antineoplastic compounds.…”

Section: Introductionmentioning

confidence: 99%

Local Intracerebral Administration of Paclitaxel with the Paclimer® Delivery System: Toxicity Study in a Canine Model

et al. 2005

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Introduction: Paclitaxel, a microtubule binding agent with potent anti-glioma activity in vitro, exhibits poor penetrance to the CNS when delivered systemically. To minimize toxicity and reach therapeutic concentrations in the CNS, paclitaxel was previously incorporated into biodegradable microspheres (Paclimer®), and the efficacy of Paclimer® was determined in a rat model of malignant glioma. In this study we report the safety of intracranial Paclimer® in a canine dose escalation toxicity study to prepare its translation into clinical scenarios.

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“…The introduction of biodegradable polymers that release chemotherapeutic agents directly into the tumor has proved to be a promising strategy at increasing the local delivery of the drug. Nitrosoureas, including BCNU, are a class of chemotherapeutic agents that have been incorporated into biodegradable polymers and, upon intracranial implantation, have demonstrated efficacy in phase III clinical trials in patients with both recurrent and newly diagnosed malignant gliomas [3,36,40]. Importantly, in contrast to systemic administration of nitrosoureas, this treatment has not been associated with systemic side effects.…”

Section: Discussionmentioning

confidence: 99%

“…Since most gliomas recur within 2 cm of the original tumor site [14,18], this anti-tumor strategy has the potential to control both local recurrence and improve overall survival. This approach has been evaluated in Phase III clinical trials with the nitrosourea, carmustine (BCNU) and has demonstrated significant improvement in survival in patients with malignant gliomas both at recurrence and at initial presentation [3,36,40].…”

Section: Introductionmentioning

confidence: 99%

Interstitial Docetaxel (Taxotere), Carmustine and Combined Interstitial Therapy: a Novel Treatment for Experimental Malignant Glioma

et al. 2006

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Docetaxel (Taxotere ® ) is a hemisynthetic, anti-cancer compound with good preclinical and clinical activity in a variety of systemic neoplasms. We tested its activity against malignant gliomas using local delivery methods. Antitumor activity was assessed in vitro against human and rat brain-tumor cell lines. For in vivo evaluation, we incorporated docetaxel into a biodegradable polymer matrix, determined associated toxicity in the rat brain, and measured efficacy at extending survival in a rat model of malignant glioma. Also, we examined the combined local delivery of docetaxel with carmustine (BCNU) against the experimental intracranial glioma. Rats bearing intracranial 9L gliosarcomas were treated 5 days after tumor implantation with various polymers (placebo, 5% docetaxel, 3.8% BCNU, or 5% docetaxel and 3.8% BCNU combination). Animals receiving docetaxel polymers (n = 15, median survival 39.1 days) had significantly improved survival over control animals (n = 12, median survival 22.5 days, P = 0.01). Similarly, animals receiving BCNU polymers (n = 15, median survival 39.3 days, 13.3% long-term survivors) demonstrated an increase in survival compared to the controls (P = 0.04). Animals receiving the combination polymers demonstrated a modest increase in survival compared to either chemotherapeutic agent alone (n = 14, median survival 54.9 days, 28.6% long-term survivors) with markedly improved survival over controls (P = 0.003). We conclude that locally delivered docetaxel shows promise as a novel antiglioma therapy and that the combination of drug regimens via biodegradable polymers may be a great therapeutic benefit to patients with malignant glioma.

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Interstitial Chemotherapy with Carmustine-loaded Polymers for High-grade Gliomas: A Randomized Double-blind Study

Abstract: Carmustine applied locally in a biodegradable polymer at the time of primary operation, seems to have a favorable effect on the life span of patients with high-grade gliomas.

Cited by 379 publications

References 11 publications

A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma

A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma

Local Intracerebral Administration of Paclitaxel with the Paclimer® Delivery System: Toxicity Study in a Canine Model

Interstitial Docetaxel (Taxotere), Carmustine and Combined Interstitial Therapy: a Novel Treatment for Experimental Malignant Glioma

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