Outcomes and Prognostic Factors in Recurrent Glioma Patients Enrolled Onto Phase II Clinical Trials

Wong, Eric T.; Hess, Kenneth R.; Gleason, Mary Jo; Jaeckle, Kurt A.; Kyritsis, Athanassios P.; Prados, Michael D.; Levin, Victor A.; Yung, W.K. Alfred

doi:10.1200/jco.1999.17.8.2572

Cited by 834 publications

(600 citation statements)

References 22 publications

Supporting

Mentioning

556

Contrasting

Unclassified

Order By: Relevance

“…In a large meta-analysis, chemotherapy for recurrent glioblastoma resulted in a PFS of nine weeks, a PFS-6 of 15% and a survival rate of 21% at 1 year (OS-1) [14]. A more recent metaanalysis confirmed these data with a PFS-6 of 16% and an OS-1 of 25% [15].…”

Section: Discussionmentioning

confidence: 93%

ACNU-based chemotherapy for recurrent glioma in the temozolomide era

et al. 2008

View full text Add to dashboard Cite

No standard of care for patients with recurrent glioblastoma has been defined since temozolomide has become the treatment of choice for patients with newly diagnosed glioblastoma. This has renewed interest in the use of nitrosourea-based regimens for patients with progressive or recurrent disease. The most commonly used regimens are carmustine (BCNU) monotherapy or lomustine (CCNU) combined with procarbazine and vincristine (PCV). Here we report our institutional experience with nimustine (ACNU) alone (n = 14) or in combination with other agents (n = 18) in 32 patients with glioblastoma treated previously with temozolomide. There were no complete and two partial responses. The progression-free survival (PFS) rate at 6 months was 20% and the survival rate at 12 months 26%. Grade III or IV hematological toxicity was observed in 50% of all patients and led to interruption of treatment in 13% of patients. Non-hematological toxicity was moderate to severe and led to interruption of treatment in 9% of patients. Thus, in this cohort of patients pretreated with temozolomide, ACNU failed to induce a substantial stabilization of disease in recurrent glioblastoma, but caused a notable hematotoxicity. This study does not commend ACNU as a therapy of first choice for patients with recurrent glioblastomas pretreated with temozolomide. (PCV). Here we report our institutional experience with nimustine (ACNU) alone (n=14) or in combination with other agents (n=18) in 32 patients with glioblastoma treated previously with temozolomide. There were no complete and two partial responses. The progression-free survival (PFS) rate at 6 months was 20% and the survival rate at 12 months 26%. Grade III or IV hematological toxicity was observed in 50% of all patients and led to interruption of treatment in 13% of patients. Non-hematological toxicity was moderate to severe and led to interruption of treatment in 9% of patients. Thus, in this cohort of patients pretreated with temozolomide, ACNU failed to induce a substantial stabilization of disease in recurrent glioblastoma, but caused a notable hematotoxicity. This study does not commend ACNU as a therapy of first choice for patients with recurrent glioblastomas pretreated with temozolomide.

show abstract

Section: Discussionmentioning

confidence: 93%

ACNU-based chemotherapy for recurrent glioma in the temozolomide era

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Treatment options are limited for patients with malignant glioma recurring despite radiation and adjuvant chemotherapy with either a nitrosourea or temozolomide [1]. Recent advances in the understanding of molecular and cytogenetic pathways involved in gliomagenesis, tumor growth, and invasion have led to the rational targeting of aberrant molecular pathways.…”

Section: Introductionmentioning

confidence: 99%

Phase I/pharmacokinetic study of CCI-779 in patients with recurrent malignant glioma on enzyme-inducing antiepileptic drugs

et al. 2004

Self Cite

View full text Add to dashboard Cite

SummaryObjectives: CCI-779 is an ester of the immunosuppressive agent sirolimus (rapamycin) that causes cell-cycle arrest at G1 via inhibition of key signaling pathways resulting in inhibition of RNA translation. Antitumor activity has been demonstrated using cell lines and animal models of malignant glioma. Patients receiving enzyme-inducing anti-epileptic drugs (EIAEDs) can have altered metabolism of drugs like CCI-779 that are metabolized through the hepatic cytochrome P450 enzyme system. The objectives of this study were to determine the pharmacokinetic profile and the maximum tolerated dose of CCI-779 in patients with recurrent malignant gliioma taking EIAEDs. Study design: The starting dose of CCI-779 was 250 mg intravenously (IV) administered weekly on a continuous basis. Standard dose escalation was performed until the maximum tolerated dose was established. Toxicity was assessed using the National Cancer Institute common toxicity criteria. Results: Two of 6 patients treated at the second dose level of 330 mg sustained a dose-limiting toxicity: grade III stomatitis, grade 3 hypercholesterolemia, or grade 4 hypertriglyceridemia. The maximum tolerated dose was reached at 250 mg IV. Pharmacokinetic profiles were similar to those previously described, but the area under the whole blood concentration-time curve of rapamycin was 1.6 fold lower for patients on EIAEDs. Conclusions: The recommended phase II dose of CCI 779 for patients on enzyme-inducing antiepileptic drugs is 250 mg IV weekly. A phase II study is ongoing to determine the efficacy of this agent.

show abstract

“…Furthermore, multiple clinical trials have found performance status, either the Karnofsky performance score or the Eastern Cooperative Oncology Group (ECOG) scale, to be a significant prognostic variable (Wong et al, 1999). Recently, the Glioma Outcomes Project data published by Laws et al (2003) confirmed that resection (compared with biopsy) is also a strong prognostic factor for survival.…”

mentioning

confidence: 99%

Phase II trial of carboplatin and etoposide for patients with recurrent high-grade glioma

et al. 2004

View full text Add to dashboard Cite

We present the results of a phase II trial of carboplatin and etoposide (CE) combination as first-line chemotherapy in patients with recurrent glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA) after surgery and radiotherapy. We assess the activity and the tolerability of this combination. 30 patients with GBM (25) and AA (5) were treated with VP-16 (etoposide) 120 mg m À2 and CBCDA (carboplatin) 100 mg m À2 for 3 days every 4 weeks. Moreover, we performed a retrospective analysis of topoisomerase IIa gene status using chromogenic in situ hybridisation. The median age was 54 years (21 -73 years); Eastern Cooperative Oncology Group performance score was 0-1 in 25 patients and 2 in five patients. All patients had been previously treated with surgical resection (21 radical resections) followed by radiation therapy (40 -60 Gy). We observed six (20%) complete responses, three (10%) partial responses and 12 (40%) stable diseases, with a response rate of 30%. The median time to progression was 4 months, while progression-free survival at 6 months was 33.3%. The median survival time was 10 months. Neutropenia occurred in 9 patients: four patients had grade 4, two patients grade 3 and three patients grade 2. In the conclusion of this clinical trial, the CE combination has shown activity in recurrent GBM and AA, with a good toxicity profile. Alterations in the copy number of topoisomerase IIa gene seem to be a rare event and in our series do not influence response to the CE combination.

show abstract

Outcomes and Prognostic Factors in Recurrent Glioma Patients Enrolled Onto Phase II Clinical Trials

Abstract: Histology is a dominant factor in determining outcome in patients with recurrent glioma enrolled onto phase II trials. Future trials should be designed with separate histology strata.

Cited by 834 publications

References 22 publications

ACNU-based chemotherapy for recurrent glioma in the temozolomide era

ACNU-based chemotherapy for recurrent glioma in the temozolomide era

Phase I/pharmacokinetic study of CCI-779 in patients with recurrent malignant glioma on enzyme-inducing antiepileptic drugs

Phase II trial of carboplatin and etoposide for patients with recurrent high-grade glioma

Contact Info

Product

Resources

About