Phase II study: WBRT ±temozolomide (TMZ) in patients with multiple brain metastases from non-small cell lung cancer (NSCLC)

e13008 Background: Brain metastases cause increasingly morbidity and mortality in patients with NSCLC. In a multicentric Austrian phase II study, we investigated feasibility and toxicity of the addition of temozolomide to whole brain radiotherapy (WBRT) in patients with multiple brain metastases of NSCLC. Methods: Consenting patients with previously untreated, multiple, and measurable brain metastases from histologically confirmed NSCLC were eligible if they were 18 years or older, were at least in RPA (recursive partitioning analysis class) class II and showed adequate organ function. Treatment consisted of WBRT (arm A) +TMZ 75mg/m2 during radiation, followed at day 28 by TMZ 100 mg/m2 day 1–14, q28 for six cycles (arm B). The primary endpoint was objective radiographic response in CNS 10 weeks after the end of WBRT. Results: 35 patients (14 women) aged 35 to 86 years, median 65 years were randomized. Eight patients were in RPA class I and 27 were in RPA class II. 13 patients were enrolled in arm A and 22 in arm B. Toxicity was mainly haematological with WHO grade 3 and 4 thrombocytopenia observed in 0/13 versus 3/22 patients, leucocytopenia in 0/13 versus 1/22 patients, and lymphocytepenia in 12/13 and 7/22 patients respectively. No severe nonhematologic toxicity occured in arm A, whereas two episodes of transient hepatic toxicity were reported in arm B. 10/13 patients of arm A and 13/22 patients of arm B showed progressive disease and dropped out of study before restaging 10 weeks after completion of WBRT. Two patients of arm A had progressive disease in CNS, all other progresses noted were systemic. At restaging there were 2 PR, 1 SD in arm A, and 1 CR, 3 PR, 6 SD in arm B. Median time to progression was 40 days in arm A and 74 days in arm B (p = 0.027). Conclusions: The addition of temozolomide to WBRT in patients with brain metastases of NSCLC yielded acceptable toxicity and promising activity, although systemic progression remained the main cause of morbidity and mortality. [Table: see text]

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Phase II study of whole brain radiotherapy with or without erlotinib in patients with multiple brain metastases from lung adenocarcinoma

Drug Design Development and Therapy ◽

10.2147/dddt.s53011 ◽

2013 ◽

pp. 1179 ◽

Cited By ~ 43

Author(s):

HongQing Zhuang ◽

zhiyong yuan ◽

Jun Wang ◽

Jingsheng wang ◽

Fengtong Li ◽

...

Keyword(s):

Brain Metastases ◽

Lung Adenocarcinoma ◽

Phase Ii ◽

Phase Ii Study ◽

Whole Brain Radiotherapy ◽

Whole Brain ◽

Multiple Brain Metastases ◽

Brain Radiotherapy

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Temozolomide added to whole brain radiotherapy in patients with multiple brain metastases of non-small-cell lung cancer: a multicentric Austrian phase II study

Wiener klinische Wochenschrift ◽

10.1007/s00508-013-0402-7 ◽

2013 ◽

Vol 125 (15-16) ◽

pp. 481-486 ◽

Cited By ~ 17

Author(s):

Marco Ronald Hassler ◽

Wolfgang Pfeifer ◽

Thomas Hendrik Knocke-Abulesz ◽

Klaus Geissler ◽

Gabriele Altorjai ◽

...

Keyword(s):

Lung Cancer ◽

Brain Metastases ◽

Small Cell Lung Cancer ◽

Phase Ii ◽

Cell Lung Cancer ◽

Phase Ii Study ◽

Whole Brain Radiotherapy ◽

Small Cell ◽

Small Cell Lung ◽

Brain Radiotherapy

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PVAG (Prednisone, Vinblastine, Doxorubicin and Gemcitabine) In Elderly Patients with Intermediate or Advanced Stage Hodgkin Lymphoma: Final Results of a Phase II Study of the German Hodgkin Study Group (GHSG).

Blood ◽

10.1182/blood.v116.21.2827.2827 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2827-2827

Author(s):

Boris Böll ◽

Teresa Halbsguth ◽

Helen Görgen ◽

Henning Bredenfeld ◽

Hans Eich ◽

...

Keyword(s):

Elderly Patients ◽

Hodgkin Lymphoma ◽

Phase Ii ◽

Poor Prognosis ◽

Progressive Disease ◽

Phase Ii Study ◽

Advanced Stage ◽

Who Grade ◽

Who Grade Iii ◽

Grade Iii

Abstract Abstract 2827 About 20% of all patients diagnosed with Hodgkin lymphoma (HL) are older than 60 years. These patients have a rather poor prognosis, particularly when presenting in intermediate or advanced stages. Besides a biologically more aggressive disease, the main reason is a drastically increased toxicity of chemo- and radiotherapy resulting in a higher treatment-related mortality and insufficient dosing of the applied treatment. In the GHSG-HD9 trial, elderly patients did not benefit from the BEACOPP regimen in terms of overall survival due to a high toxicity related death rate. In order to improve tolerability, the PVAG regimen (prednisone, vinblastine, doxorubicin, and gemcitabine) was developed. This is a modification of the ABVD regimen in which bleomycin and dacarbazine were replaced by prednisone and gemcitabine. Here we report for the first time on the final analysis of this multi-center phase II study for elderly HL patients. 61 patients were recruited between 2004 and 2007. 2 patients were excluded due to histology review not confirming HL, resulting in 59 patients with intermediate- or advanced-stage HL aged between 60 and 75 years. Treatment consisted of 6 cycles PVAG in patients achieving a complete remission (CR) after 4 cycles or 8 cycles PVAG in case of partial remission (PR) after 4 cycles. Patients who did not achieve CR after the end of chemotherapy received additional radiotherapy. Primary endpoints were administration of adequate dose without excessive delays, and response rate 3 months after end of treatment. Secondary endpoints included WHO grade III/IV toxicities, and occurrence of early progression. 59 patients with a median age of 68 years were evaluated, of which 59% were male and 93% had advanced stage disease. The relative dose intensity (relative dose divided by relative chemotherapy duration) was at least 80% in 44 patients (76%). Regarding the single cycles, of which 85% started without major delay (max. 1 day), the mean relative dose of all agents was slightly decreasing over time but always exceeded 90%. WHO grade III/IV toxicities were documented in 43 patients (75%). Only 3 patients terminated CT because of excessive toxicity. 10 Patients (17%) received consolidating radiotherapy. In total, 46 patients responded with CR/CRu (78%; 95% CI: 65% to 88%), 2 with PR (3%), 2 with no change (3%) and 4 with progressive disease (7%). 3 patients died before restaging with unknown response and in 2 patients treatment outcome is unknown. With a median observation time of 37 months, 6 patients (10%) had progressive disease and 9 patients (15%) relapsed. In total, 10 patients died from relapsing or progressing HL, 2 from second malignancies (one of lung cancer after 23 months, and one of AML after 25 months) and 5 patients due to other reasons. Overall 17 patients (29%, 95% CI: 18% to 42%) have died so far. In conclusion, PVAG is safe and feasible in Hodgkin patients older than 60. The PFS indicates activity of this regimen in this poor prognosis patient cohort. However, a controlled randomized trial to determine the best treatment in this patient population is warranted. This trial was registered at www.clinicaltrials.gov as #NCT00147875. Disclosures: No relevant conflicts of interest to declare.

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Multidisciplinary Approach to Brain Metastasis from Melanoma: The Emerging Role of Systemic Therapies

American Society of Clinical Oncology Educational Book ◽

10.14694/edbook_am.2013.33.393 ◽

2013 ◽

pp. 393-398 ◽

Cited By ~ 4

Author(s):

Georgina V. Long ◽

Kim A. Margolin

Keyword(s):

Brain Metastasis ◽

Brain Metastases ◽

Phase Ii ◽

Phase Ii Study ◽

Performance Status ◽

Local Therapy ◽

Whole Brain Radiotherapy ◽

Brain Radiotherapy ◽

First Line Therapy ◽

Melanoma Brain Metastases

Melanoma brain metastases are common, difficult to treat, and carry a poor prognosis. Until recently, systemic therapy was ineffective. Local therapy (including surgery, stereotactic radiotherapy, and whole brain radiotherapy) was considered the only option for a chance of disease control in the brain, and was highly dependent on the patient's performance status and age, number and size of brain metastases, and the presence of extracranial metastases. Since 2010, three drugs have demonstrated activity in progressing or “active” brain metastases including the anti-CTLA4 antibody ipilimumab (phase II study of 72 patients), and the BRAF inhibitors dabrafenib (phase II study of 172 patients, both previously treated and untreated brain metastases) and vemurafenib (a pilot study of 24 patients with heavily pretreated brain metastases). The challenge and unanswered question for clinicians is how to sequence all the available therapies, both local and systemic, to optimize the patient's quality of life and survival. This is an area of intense clinical research. The treatment of patients with melanoma brain metastases should be discussed by a multidisciplinary team of melanoma experts including a neurosurgeon, medical oncologist, and radiation oncologist. Important clinical features that help determine appropriate first line therapy include single compared with solitary brain metastasis, resectablity, BRAF mutation status of melanoma, rate of progression/performance status, and the presence of extracranial disease.

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Icotinib and whole brain radiotherapy (WBRT) for patients with brain metastases from non-small cell lung cancer (NSCLC): Preliminary results of a phase II study.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e19073 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e19073-e19073

Author(s):

Fan Yun ◽

Zhiyu Huang ◽

Lei Gong ◽

Haifeng Yu ◽

Haiyan Yang ◽

...

Keyword(s):

Brain Metastases ◽

Phase Ii ◽

Kinase Inhibitors ◽

Advanced Nsclc ◽

Response Rate ◽

Phase Ii Study ◽

Whole Brain Radiotherapy ◽

Phase Iii ◽

Double Blind ◽

The Mean

e19073 Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, have shown efficacy in advanced NSCLC with brain metastases (BM). Icotinib is a new EGFR-TKI. A randomized, double blind phase III trial proved that icotinib was non-inferior to gefitinib in advanced NSCLC. We have conducted a phase II study to evaluate the efficacy and safety of icotinib in combination with WBRT in Chinese NSCLC patients with BM. Methods: From January 2012 to January 2013, 20 patients aged 18-75 years with ECOG PS 0-2 and BM from NSCLC,were recruited regardless of EGFR status. The treatment comprised icotinib 125mg, TID concurrently with WBRT (30Gy/10f/2w). CSF and plasma samples were collected at the same time from 10 patients at least 5 days after icotinib treatment. The concentrations of icotinib in the CSF and plasma were measured by high performance liquid chromatography coupled with tandem mass spectrometry. The primary end point was progression-free survival (PFS) . Additional end points were response rate, safety and CSF concentrations of icotinib. Results: The median PFS was 7.3 months [95% confidence interval (CI) 4. 2-9.8]. Patients with EGFR mutation-positive disease had significantly longer median PFS versus EGFR wild-type disease [NR versus 4.2 months (95% CI 2.9-5.1); P = 0.000]. The CNS response rates were 25% complete response (n=5), 55% partial response (n= 11), 15% stable disease (n=3), and 5% progressive disease (n =1). The overall CNS response rate was 80% (n = 16). The most common adverse events were rash (40.0%), diarrhea (15.0%),nausea (45.0%), vomiting (20.0%), headache (35.0%)and fatigue (45.0%). And no patient experienced grade ≥ 3 toxicity. The mean plasma and CSF concentrations of icotinib were 936.47 ± 503.80 and 8.93 ± 8.01 ng/ml, respectively, and the mean ratio of CSF-plasma concentration was 1.04% ± 0.95. Conclusions: Icotinib was well tolerated and showed promising activity in combination with WBRT in patients with BM from NSCLC. The concentrations of icotinib in CSF were low. Further randomized trials are warranted. Clinical trial information: NCT01514877.

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