ACTR-89. KARNOFSKY PERFORMANCE STATUS AND STEROID USE IN PHASE II TRIAL OF BEVACIZUMAB AND TEMOZOLOMIDE FOR UPFRONT TREATMENT OF ELDERLY PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

1085 Background: Oral vinorelbine (VNR) is particularly useful in elderly patients due to its favorable toxicity profile. Several studies demonstrated that this drug seems to represent an active treatment for metastatic breast cancer (MCB). We evaluated the clinical efficacy and tolerance of metronomic chemotherapy with oral VNR. Methods: Women were eligible if they had a histologically proven untreated MBC and were > 70 years old. A two-staged Simon accrual design was adopted for this phase II trial. Patients were required to have negative estrogen receptor status, at least one bidimensionally measurable target lesion, Karnofsky performance status >70; life expectancy > 3 months. Each patient received oral vinorelbine 80 mg/m2 fractionated in days 1, 3, and 5, three week on-one week off, every 4 weeks, for a maximum of six cycles unless disease progression or unacceptable toxicity. Results: Thirty-two patients with MBC were eligible, assessable for response, and toxicity. The median age was 75 years (range 70–84), sixteen patients (50%) had a Karnofsky performance status of 90–100. The main comorbidities recorded were: hypertension in 9 (28%) patients and diabetes mellitus in 6 (19%). The overall response rate (on an intent-to-treat basis) was 41% (13 of 32; 95% CI, 20%-54%). Two complete response and 11 partial responses were noted. In addition, other 10 patients (31%) had stable disease of > 4 months duration, and 9 patients (28 %) had disease progression. Median time to disease progression was 7.1 months and median overall survival was 12.7 months. The schedule was well tolerated, grade 3 toxicity was observed only in two patients. Conclusions: Metronomic oral VNR can be safely administered to elderly patients with MBC and is active in this population. Final data analysis will be presented. No significant financial relationships to disclose.

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Temozolomide plus bevacizumab in elderly patients with newly diagnosed glioblastoma and poor performance status: An Anocef phase II trial.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.2020 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 2020-2020 ◽

Cited By ~ 10

Author(s):

German Reyes-Botero ◽

Jerôme Honnorat ◽

Oliver L. Chinot ◽

Luc Taillandier ◽

Isabelle Catry-Thomas ◽

...

Keyword(s):

Elderly Patients ◽

Phase Ii ◽

Phase Ii Trial ◽

Karnofsky Performance Status ◽

Performance Status ◽

Brain Mri ◽

Haematological Toxicity ◽

Self Care ◽

Progression Free Survival ◽

Poor Performance Status

2020 Background: The optimal treatment of glioblastoma multiforme (GBM) in elderly patients (age ≥70 years) with impaired functional status (Karnofsky performance status, KPS<70) remains to be established. A previous study using temozolomide (TMZ) alone suggested an increase in median overall survival (OS) compared to supportive care (25 weeks vs. 12-16 weeks, respectively). Median progression-free survival (PFS) was 16 weeks and 26% of patients became transiently capable of self-care (IK>70) (J Clin Oncol. 2011; 29: 3050-5). The present clinical trial evaluated the efficacy and safety of the combination of TMZ with bevacizumab (BV) as an initial treatment for elderly patients with GBM and KPS<70. Methods: Patients aged ≥ 70 years with KPS < 70 and a newly supratentorial GBM diagnosed by biopsy were eligible for this multicentric, prospective and non-randomised phase II trial. The primary endpoint was the OS and secondary endpoints included median PFS, quality of life, safety and cognition. Treatment consisted of TMZ 130-150 mgs/m2/d for 5 days every 4 weeks plus BV 10mgs/kg every 2 weeks, until 12 cycles or tumoral progression. Neither surgical resection nor radiotherapy was performed. Follow-up included clinical assessment every 2 weeks and brain MRI every 8 weeks. Results: Between October 2010 and March 2012, 66 patients (median age, 77 years; median KPS, 60) were enrolled. Median OS was 24 weeks (95% CI, 19-27.6) and median PFS was 16 weeks (95% CI, 13.1–19.3). Twenty-five patients (38%) became transiently capable of self-care (IK>70). Grade 3 and 4 haematological toxicity occurred in 13(19.6%) cases, whereas non-haematological toxicities were reported in 21(32%), including high blood pressure in 7(10%), thromboembolic events in 3(4.5%), intracerebral haemorrhage in 2(3%) and intestinal perforation in 2(3%) cases. Conclusions: This study confirms that TMZ-based treatment is of help in elderly GBM patients with poor KPS. However, the addition of bevacizumab does not appear to be of benefit in term of PFS and OS.

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Phase II trial of bevacizumab and temozolomide for upfront treatment of elderly patients with newly diagnosed glioblastoma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.2012 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 2012-2012

Author(s):

Phioanh Leia Nghiemphu ◽

Hye Hyun Bahng ◽

Albert Lai ◽

Nadia Faiq ◽

William H. Yong ◽

...

Keyword(s):

Clinical Trial ◽

Overall Survival ◽

Adverse Events ◽

Elderly Patients ◽

Tumor Progression ◽

Phase Ii ◽

Phase Ii Trial ◽

Performance Status ◽

Newly Diagnosed ◽

Safety And Efficacy

2012 Background: Randomized clinical trials in newly diagnosed, elderly GBM patients have shown that treatment with temozolomide chemotherapy is at least equivalent to treatment with radiotherapy. Glioblastoma in elderly patients may also have high angiogenic activities. Bevacizumab is an antiangiogenic agent, a humanized monoclonal antibody directed against the vascular endothelial growth factor. We conduct a clinical trial of temozolomide and bevacizumab to evaluate the safety and efficacy of this combination in the treatment of elderly patients with newly diagnosed GBM, good performance status, and willing to forgo upfront treatment with radiation therapy. Methods: This is a phase II trial of newly diagnosed GBM patients age ≥70 with no prior treatments other than surgery and Karnofsky Performance Status (KPS) ≥60. Patients receive treatments 4-6 weeks after surgery with bevacizumab (10mg/kg every 2 weeks) and temozolomide (150-200 mg/m2 for 5 days out of 28 days, up to 12 cycles) until tumor progression. Primary outcome measures are overall survival and safety evaluations. Results: From June 2010 to January 2016, 50 GBM patients enrolled in this study. To date, all patients have tumor progression and 3 are still alive. The median age is 75 (range 70 - 87), and median KPS is 80 (range 60-100). 15 patients have a gross total resection. 26 out of 49 patients with tissues available for evaluation have methylation of the MGMT promoter, and no patient has IDH-1 mutation. Median overall survival is 12.3 months (14.8 months for those with methylation of MGMT, 10.0 months for unmethylated MGMT). Serious adverse events related to treatments include wound healing problems (2), CNS hemorrhage (3), pulmonary embolism (4), and bowel perforation (1). Serious hematological adverse events include thrombocytopenia (3) and neutropenia (5). Conclusions: For patients with newly diagnosed GBM age ≥70, KPS ≥60, treatment with temozolomide and bevacizumab may show promising survival benefits and have tolerable side effects. More detailed safety and efficacy analysis will be presented. Clinical trial information: NCT01149850.

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Presentation, management, and outcome of newly diagnosed glioblastoma in elderly patients

Journal of Neurosurgery ◽

10.3171/2012.10.jns112268 ◽

2013 ◽

Vol 118 (4) ◽

pp. 786-798 ◽

Cited By ~ 53

Author(s):

Shota Tanaka ◽

Fredric B. Meyer ◽

Jan C. Buckner ◽

Joon H. Uhm ◽

Elizabeth S. Yan ◽

...

Keyword(s):

Elderly Patients ◽

Adjuvant Treatment ◽

Karnofsky Performance Status ◽

Combined Therapy ◽

Performance Status ◽

Progression Free Survival ◽

Postoperative Hemorrhage ◽

Neurological Deficits ◽

Newly Diagnosed ◽

Newly Diagnosed Glioblastoma

Object Optimum management for elderly patients with newly diagnosed glioblastoma (GBM) in the temozolomide (TMZ) era is not well defined. The object of this study was to clarify outcomes in this population. Methods The authors retrospectively reviewed 105 consecutive cases involving elderly patients (age ≥ 65 years) with newly diagnosed GBM who were treated at the Mayo Clinic between 2003 and 2008. Results The patients' median age was 74 years (range 66–87 years), and the median Karnofsky Performance Status (KPS) score was 80 (range 40–90). Half of the patients underwent biopsy and half underwent resection. Patients with deep-seated lesions (19 patients [18%]) or multifocal lesions (34 patients [32%]) were more likely to have biopsy than resection (p = 0.0001 and 0.0009, respectively). New persistent neurological deficits developed in 7 patients (6.7%). Postoperative hemorrhage occurred in 6 patients (5.7%), all of whom underwent biopsy. Complete follow-up data regarding adjuvant treatment was available in 84 patients. Forty-one (49%) were treated with chemotherapy (mostly TMZ) and radiation therapy (RT), and 23 (27%) with RT alone. Nineteen (23%) received only palliative care after surgery (more common with biopsy, p = 0.03). Chemotherapy complications occurred in 28.6% (Grade 3 or 4 hematological complications in 11.9%). The median values for progression-free survival (PFS) and overall survival (OS) were 3.5 and 5.5 months. In a multivariate analysis, younger age (p = 0.03, risk ratio [RR] 0.34, 95% CI 0.13–0.89), single lesion (p = 0.02, RR 0.51, 95% CI 0.30–0.89), resection (p = 0.04, RR 0.54, 95% CI 0.31–0.94), and adjuvant treatment (p = 0.0001, RR 0.24, 95% CI 0.11–0.49) were associated with better OS. Only adjuvant treatment was significantly associated with prolonged PFS (p = 0.0007, RR 0.27, 95% CI 0.13–0.57). With combined therapy with resection, RT, and chemotherapy, the median PFS and OS were 8 and 12.5 months, respectively. Conclusions The prognosis for GBM worsens with increasing age in elderly patients. With important risks, resection and adjuvant treatment are associated with prolonged survival. Although selection bias cannot be excluded in this retrospective study, advanced age alone should not necessarily preclude optimal resection followed by adjuvant radiochemotherapy.

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