Phase II trial of irinotecan plus celecoxib in adults with recurrent malignant glioma

Abstract

BACKGROUND In the current study, the authors report a Phase II trial of irinotecan (CPT‐11), a topoisomerase I inhibitor active against malignant glioma (MG), with celecoxib, a selective COX‐2 inhibitor, among MG patients with recurrent disease. METHODS Patients with MG at any type of recurrence received CPT‐11, administered as a 90‐minute intravenous infusion on Weeks 1, 2, 4, and 5 of each 6‐week cycle plus celecoxib, which was administered continuously at a dose of 400 mg twice a day. CPT‐11 was given at a dose of 350 mg/m2 for patients receiving enzyme‐inducing antiepileptic drugs (EIAEDs) and at a dose of 125 mg/m2 for those patients not receiving EIAEDs. Assessments were performed after every cycle. The primary endpoint was radiographic response and the secondary endpoints were progression‐free survival (PFS), overall survival (OS), and therapeutic safety. RESULTS Thirty‐four of the 37 patients enrolled in the current study (92%) were diagnosed with recurrent GBM and 3 patients (8%) were diagnosed with recurrent anaplastic astrocytoma (AA). Twenty‐one patients were receiving EIAEDs and 16 patients were not. The median follow‐up time was 76.9 weeks. Concomitant CPT‐11 plus celecoxib was found to be well tolerated and safe. Hematologic toxicities of ≥ Grade 3 (according the second version of the Common Toxicity Criteria of the National Cancer Institute) reportedly complicated 8.6% of treatment courses. Grade 3 diarrhea, the most commonly reported nonhematologic toxicity, occurred with equal frequency (8%), regardless of whether the patient was receiving EIAED. Six patients (16%), all whom were diagnosed with recurrent GBM, achieved an objective radiographic response whereas an additional 13 patients (35%) achieved stable disease. The median PFS was 11.0 weeks and the 6‐month PFS was reported to be 25.1%. The median OS was 31.5 weeks. CONCLUSIONS The results of the current study confirm that CPT‐11 plus celecoxib can be safely administered concurrently at full dose levels, and that this regimen has encouraging activity among heavily pretreated patients with recurrent MG. Cancer 2005. © 2005 American Cancer Society.

Neurocognitive functioning and quality of life in patients with recurrent malignant gliomas treated on a phase Ib trial evaluating topotecan by convection-enhanced delivery

“…Prior therapy consisted of surgery, radiotherapy, and chemotherapy in 12 participants (75%); surgery and radiotherapy in 3 participants (18.7%); and radiotherapy and chemotherapy in one participant (6.3%) with biopsy-proven glioblastoma multiforme. The median time from diagnosis to treatment was 14.5 months, and the median tumor volume treated was 14.45 cm 3 . Based on postoperative imaging, catheter placement was optimized in 2 participants without altering the treatment protocol.…”

“…Furthermore, recurrence is typically accompanied by progressive physical and cognitive debilitation. 3 As a result, 2 secondary outcome measures have emerged in neurooncology trials: evaluations of neurocognitive function (NCF) and quality of life (QoL).…”

An algorithm for chemotherapy treatment of recurrent glioma patients after temozolomide failure in the general oncology setting

“…Similarly, ACNU, another nitrosourea given alone or in combination with teniposide or cytarabine in patients with GBM after TMZ failure resulted in limited activity and considerable toxicity [69]. The combination of CPT-11 and celecoxib, a selective COX-2 inhibitor was well tolerated and had a marginal activity against heavily pretreated recurrent glioma (mostly GBM) patients with PFS6 of 25.1% [70].…”

Therapeutic Inhibition of the Epidermal Growth Factor Receptor in High-Grade Gliomas: Where Do We Stand?

“…One of the newer drugs that have been used in recurrent glioma is irinotecan (Camptosar, Pfizer Pharmaceuticals), a topoisomerase I inhibitor with good penetration of the blood-brain barrier. Several clinical trials were conducted and showed response rates from 2.2% to 16% (37,50,51). Progression-free survival after 6 months was reported to be 25% to 43% in some studies (50,51).…”

“…Several clinical trials were conducted and showed response rates from 2.2% to 16% (37,50,51). Progression-free survival after 6 months was reported to be 25% to 43% in some studies (50,51). More recently, antiangiogenic compounds were reintroduced into the therapeutic field of recurrent malignant glioma.…”