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1.
J Clin Oncol ; 33(2): 189-94, 2015 Jan 10.
Article in English | MEDLINE | ID: mdl-25452446

ABSTRACT

PURPOSE: Overexpression of COX-2 correlates with advanced stage and worse outcomes in non-small-cell lung cancer (NSCLC), possibly as a result of elevated levels of COX-2-dependent prostaglandin E2 (PGE2). Exploratory analyses of studies that used COX-2 inhibitors have demonstrated potentially superior outcome in patients in whom the urinary metabolite of PGE2 (PGE-M) is suppressed. We hypothesized that patients with disease defined by PGE-M suppression would benefit from the addition of apricoxib to second-line docetaxel or pemetrexed. PATIENTS AND METHODS: Patients with NSCLC who had disease progression after one line of platinum-based therapy, performance status of 0 to 2, and normal organ function were potentially eligible. Only patients with a ≥ 50% decrease in urinary PGE-M after 5 days of treatment with apricoxib could enroll. Docetaxel 75 mg/m(2) or pemetrexed 500 mg/m(2) once every 21 days per the investigator was administered with apricoxib or placebo 400 mg once per day. The primary end point was progression-free survival (PFS). Exploratory analysis was performed regarding baseline urinary PGE-M and outcomes. RESULTS: In all, 101 patients completed screening, and 72 of the 80 who demonstrated ≥ 50% suppression were randomly assigned to apricoxib or placebo. Toxicity was similar between the arms. No improvement in PFS was seen with apricoxib versus placebo. The median PFS for the control arm was 97 days (95% CI, 52 to 193 days) versus 85 days (95% CI, 67 to 142 days) for the experimental arm (P = .91). CONCLUSION: Apricoxib did not improve PFS, despite biomarker-driven patient selection.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/urine , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Prostaglandins/urine , Aged , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/urine , Cyclooxygenase 2/metabolism , Disease-Free Survival , Docetaxel , Double-Blind Method , Drug Administration Schedule , Female , Glutamates/administration & dosage , Guanine/administration & dosage , Guanine/analogs & derivatives , Humans , Kaplan-Meier Estimate , Lung Neoplasms/pathology , Lung Neoplasms/urine , Male , Middle Aged , Neoplasm Staging , Patient Selection , Pemetrexed , Pyrroles/administration & dosage , Pyrroles/adverse effects , Sulfonamides/administration & dosage , Sulfonamides/adverse effects , Taxoids/administration & dosage , Treatment Outcome
2.
Neuro Oncol ; 4(4): 261-7, 2002 10.
Article in English | MEDLINE | ID: mdl-12356356

ABSTRACT

Temozolomide is a novel second-generation oral alkylating agent with demonstrated efficacy and safety in patients with recurrent glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA). A multicenter phase II trial was conducted to determine the efficacy and safety of temozolomide before radiotherapy in patients with newly diagnosed GBM and AA. Fifty-seven patients (51 adult, 6 pediatric) with newly diagnosed supratentorial GBM or AA were treated with temozolomide (200 mg/m ( 2 ) per day for 5 consecutive days every 28 days) for a maximum of 4 cycles. All patients were then treated with external beam radiotherapy. Twenty-two patients (39%) achieved objective response, including 6 (11%) with complete response (CR) and 16 (28%) with partial response (PR). Additionally, 18 (32%) patients had stable disease (SD). Of 21 patients (18 adult, 3 pediatric) with AA, 2 (10%) achieved CR, 5 (24%) achieved PR, and 8 (38%) had SD. Among adult patients with AA, the median progression-free and overall survival rates were 7.6 and 23.5 months, respectively. Among 36 patients (33 adult, 3 pediatric) with GBM, 4 (11%) had CR, 11 (31%) had PR, and 10 (28%) had SD. The median progression-free and overall survival rates among adult patients with GBM were 3.9 and 13.2 months, respectively. Temozolomide was safe and well tolerated in adult and pediatric patients. Grades 3 and 4 adverse events were reported in 16 (28%) and 7 (12%) patients, respectively. Temozolomide was safe and effective in treating newly diagnosed GBM and AA before radiotherapy. This pre-irradiation treatment approach appears promising, but will require additional evaluation in comparative studies.


Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Dacarbazine/analogs & derivatives , Dacarbazine/therapeutic use , Glioma/drug therapy , Supratentorial Neoplasms/drug therapy , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Glioma/pathology , Glioma/radiotherapy , Humans , Male , Middle Aged , Multicenter Studies as Topic , Supratentorial Neoplasms/pathology , Supratentorial Neoplasms/radiotherapy , Survival Rate , Temozolomide , Treatment Outcome
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